Pharmacy and Poisons Board: Applications

Protocol No.	Study Title	Principal Investigator(s)	Name of Site / County	Pages	Clear
Application Submission Dates-to- clear!

#	Protocol No	Study Title	Investigator(s) & Site(s)
446.	ECCT/19/10/03	Smoking Cessation Study for PLHIV Optimizing Smoking Cessation Interventions For People Living With Human Immunodeficiency Virus in Nairobi, Kenya	Principal Investigator(s) 1. Dr. Seth Scott Himelhoch Seth Scott Himelhoch Site(s) in Kenya Mathari National Teaching and Referral Hospital	View
447.	ECCT/21/03/02	PB-SAM Pancreatic Enzymes and Bile Acids: A Non-Antibiotic approach to Treat Intestinal Dysbiosis in Acutely Ill Severely Malnourished Children.	Principal Investigator(s) 1. Robert Bandsma Site(s) in Kenya 1. Kilifi County Hospital (Kilifi county) 2. Coast General Hospital (Mombasa county) 3. Mbagathi Hospital (Nairobi City county) 4. Migori County Hospital (Migori county)	View
448.	ECCT/08/20/01	Partners PrEP Study Parallel comparison of Tenofovir and Emtricitabine/Tenofovir pre exposure prophylaxis to prevent HIV-1 acquisition within HIV-1 discordant couples	Principal Investigator(s) 1. James Njogu Kiarie 2. CAREY FARQUHAR, 3. Grace John Stewart Site(s) in Kenya 1. Nairobi (Nairobi City county) 2. Thika (Kiambu county) 3. Eldoret (Uasin Gishu county) 4. Kisumu (Kisumu county)	View
449.	ECCT/08/08/03	Partners PrEP Study Parallel Comparison of Tenofovir and Emtricitabine/Tenofovir Pre-exposure Prophylaxis to Prevent HIV-1 Acquisition within HIV-1 Discordant Couples.	Principal Investigator(s) 1. Prof. Connie Celum Site(s) in Kenya 1. Kenya- Eldoret (Uasin Gishu county) 2. Kenya â€“ Nairobi (Nairobi City county) 3. Kenya â€“ Kisumu (Kisumu county) 4. Kenya â€“ Thika (Uasin Gishu county)	View
450.	ECCT/08/06/01	PARTNERS PrEP Parallel Comparison of Tenofovir and Emtricitabine/tenofovir Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition within HIV-1 Discordant Couples	Principal Investigator(s) 1. Elizabeth Anne Bukusi Site(s) in Kenya 1. Kisumu site (Kisumu county)	View

History
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Request History
4 previous requests available
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Session
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Session
- Config(array)
  userAgent9c3d2c89526db53b7b69e8c9faa06145
  time1746153958
  countdown10
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Request
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Request

Cake Params
- plugin(null)
- controllerapplications
- actionindex
- named(array)
  page90
  sortstudy_title
  directionasc
  approved1
- pass(empty)
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- paging(array)
  Application(array)
  page90
  current5
  count502
  prevPage(true)
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  order(array)
  Application.study_titleasc
  limit5
  options(array)
  page90
  order(array)
  Application.study_titleasc
  sortstudy_title
  directionasc
  paramTypenamed
Post data
- Application(array)
  approved1
Query string

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Current Route
- keys(array)
  0controller
  1action
- options(empty)
- defaults(array)
  plugin(null)
- template/:controller/:action/*
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Sql Logs

default

Total Time: 135 ms
Total Queries: 19 queries

Query	Affected	Num. rows	Took (ms)	Actions
SELECT `Application`.`id`, `Application`.`user_id`, `Application`.`trial_status_id`, `Application`.`abstract_of_study`, `Application`.`study_title`, `Application`.`laymans_summary`, `Application`.`short_title`, `Application`.`protocol_no`, `Application`.`version_no`, `Application`.`date_of_protocol`, `Application`.`study_drug`, `Application`.`disease_condition`, `Application`.`product_type_biologicals`, `Application`.`product_type_proteins`, `Application`.`product_type_immunologicals`, `Application`.`product_type_vaccines`, `Application`.`product_type_hormones`, `Application`.`product_type_toxoid`, `Application`.`product_type_chemical`, `Application`.`product_type_medical_device`, `Application`.`product_type_chemical_name`, `Application`.`product_type_medical_device_name`, `Application`.`comparator`, `Application`.`comparator_name`, `Application`.`comparator_registered`, `Application`.`comparator_countries`, `Application`.`ecct_not_applicable`, `Application`.`ecct_ref_number`, `Application`.`email_address`, `Application`.`applicant_covering_letter`, `Application`.`applicant_protocol`, `Application`.`applicant_patient_information`, `Application`.`applicant_investigators_brochure`, `Application`.`applicant_investigators_cv`, `Application`.`applicant_signed_declaration`, `Application`.`applicant_financial_declaration`, `Application`.`applicant_gmp_certificate`, `Application`.`applicant_indemnity_cover`, `Application`.`applicant_opinion_letter`, `Application`.`applicant_approval_letter`, `Application`.`applicant_statement`, `Application`.`applicant_participating_countries`, `Application`.`applicant_addendum`, `Application`.`applicant_fees`, `Application`.`applicant_complete_form`, `Application`.`applicant_impd`, `Application`.`applicant_prev_data`, `Application`.`applicant_stability_data`, `Application`.`applicant_analysis_cert`, `Application`.`applicant_pictorial_sample`, `Application`.`applicant_gcp_training`, `Application`.`applicant_dsmb_charter`, `Application`.`applicant_detailed_budget`, `Application`.`applicant_indemnity_pi`, `Application`.`applicant_practice_license`, `Application`.`applicant_registration_ctr`, `Application`.`applicant_pan_african`, `Application`.`applicant_hard_copies`, `Application`.`applicant_signed_checklist`, `Application`.`statistical_analysis_plan`, `Application`.`applicant_contractual_agreement`, `Application`.`declaration_applicant`, `Application`.`declaration_date1`, `Application`.`declaration_principal_investigator`, `Application`.`declaration_date2`, `Application`.`placebo_present`, `Application`.`study_objectives`, `Application`.`principal_inclusion_criteria`, `Application`.`principal_exclusion_criteria`, `Application`.`primary_end_points`, `Application`.`scope_diagnosis`, `Application`.`scope_prophylaxis`, `Application`.`scope_therapy`, `Application`.`scope_safety`, `Application`.`scope_efficacy`, `Application`.`scope_pharmacokinetic`, `Application`.`scope_pharmacodynamic`, `Application`.`scope_bioequivalence`, `Application`.`scope_dose_response`, `Application`.`scope_pharmacogenetic`, `Application`.`scope_pharmacogenomic`, `Application`.`scope_pharmacoecomomic`, `Application`.`scope_others`, `Application`.`scope_others_specify`, `Application`.`trial_human_pharmacology`, `Application`.`trial_administration_humans`, `Application`.`trial_bioequivalence_study`, `Application`.`trial_other`, `Application`.`trial_other_specify`, `Application`.`trial_therapeutic_exploratory`, `Application`.`trial_therapeutic_confirmatory`, `Application`.`trial_therapeutic_use`, `Application`.`design_controlled`, `Application`.`site_capacity`, `Application`.`staff_numbers`, `Application`.`other_details_explanation`, `Application`.`other_details_regulatory_notapproved`, `Application`.`other_details_regulatory_approved`, `Application`.`other_details_regulatory_rejected`, `Application`.`other_details_regulatory_halted`, `Application`.`estimated_duration`, `Application`.`design_controlled_randomised`, `Application`.`design_controlled_open`, `Application`.`design_controlled_single_blind`, `Application`.`design_controlled_double_blind`, `Application`.`design_controlled_parallel_group`, `Application`.`design_controlled_cross_over`, `Application`.`design_controlled_other`, `Application`.`design_controlled_specify`, `Application`.`design_controlled_comparator`, `Application`.`design_controlled_other_medicinal`, `Application`.`design_controlled_placebo`, `Application`.`design_controlled_medicinal_other`, `Application`.`design_controlled_medicinal_specify`, `Application`.`single_site_member_state`, `Application`.`location_of_area`, `Application`.`single_site_physical_address`, `Application`.`single_site_contact_person`, `Application`.`single_site_telephone`, `Application`.`multiple_sites_member_state`, `Application`.`multiple_countries`, `Application`.`multiple_member_states`, `Application`.`number_of_sites`, `Application`.`multi_country_list`, `Application`.`data_monitoring_committee`, `Application`.`total_enrolment_per_site`, `Application`.`total_participants_worldwide`, `Application`.`population_less_than_18_years`, `Application`.`population_utero`, `Application`.`population_preterm_newborn`, `Application`.`population_newborn`, `Application`.`population_infant_and_toddler`, `Application`.`population_children`, `Application`.`population_adolescent`, `Application`.`population_above_18`, `Application`.`population_adult`, `Application`.`population_elderly`, `Application`.`gender_female`, `Application`.`gender_male`, `Application`.`subjects_healthy`, `Application`.`subjects_patients`, `Application`.`subjects_vulnerable_populations`, `Application`.`subjects_women_child_bearing`, `Application`.`subjects_women_using_contraception`, `Application`.`subjects_pregnant_women`, `Application`.`subjects_nursing_women`, `Application`.`subjects_emergency_situation`, `Application`.`subjects_incapable_consent`, `Application`.`subjects_specify`, `Application`.`subjects_others`, `Application`.`subjects_others_specify`, `Application`.`investigator1_given_name`, `Application`.`investigator1_middle_name`, `Application`.`investigator1_family_name`, `Application`.`investigator1_qualification`, `Application`.`investigator1_professional_address`, `Application`.`investigator1_telephone`, `Application`.`investigator1_email`, `Application`.`organisations_transferred_`, `Application`.`number_participants`, `Application`.`notification`, `Application`.`approval_date`, `Application`.`submitted`, `Application`.`deleted`, `Application`.`deleted_date`, `Application`.`deactivated`, `Application`.`date_submitted`, `Application`.`is_child`, `Application`.`unsubmitted`, `Application`.`initial_date_submitted`, `Application`.`admin_stopped`, `Application`.`admin_stopped_reason`, `Application`.`approved`, `Application`.`approved_reason`, `Application`.`final_report`, `Application`.`implication_results`, `Application`.`quantity_imported`, `Application`.`quantity_dispensed`, `Application`.`quantity_destroyed`, `Application`.`quantity_exported`, `Application`.`balance_site`, `Application`.`final_date`, `Application`.`modified`, `Application`.`created`, `Application`.`total_sites`, `Application`.`ecitizen_invoice` FROM `ctr`.`applications` AS `Application` WHERE `Application`.`approved` = 2 AND `Application`.`submitted` = '1' AND `Application`.`deactivated` = '0' AND `Application`.`deleted` = '0' ORDER BY `Application`.`study_title` asc LIMIT 445, 5	5	5	126	maybe slow
SELECT `InvestigatorContact`.`id`, `InvestigatorContact`.`application_id`, `InvestigatorContact`.`given_name`, `InvestigatorContact`.`middle_name`, `InvestigatorContact`.`family_name`, `InvestigatorContact`.`qualification`, `InvestigatorContact`.`professional_address`, `InvestigatorContact`.`telephone`, `InvestigatorContact`.`email`, `InvestigatorContact`.`created`, `InvestigatorContact`.`modified` FROM `ctr`.`investigator_contacts` AS `InvestigatorContact` WHERE `InvestigatorContact`.`application_id` IN (829, 967, 221, 202, 90)	7	7	2	maybe slow
SELECT `SiteDetail`.`id`, `SiteDetail`.`application_id`, `SiteDetail`.`county_id`, `SiteDetail`.`site_name`, `SiteDetail`.`physical_address`, `SiteDetail`.`contact_details`, `SiteDetail`.`contact_person`, `SiteDetail`.`site_capacity`, `SiteDetail`.`misc`, `SiteDetail`.`created`, `SiteDetail`.`modified` FROM `ctr`.`site_details` AS `SiteDetail` WHERE `SiteDetail`.`application_id` IN (829, 967, 221, 202, 90)	14	14	2	maybe slow
SELECT `County`.`id`, `County`.`county_name`, `County`.`created`, `County`.`modified` FROM `ctr`.`counties` AS `County` WHERE `County`.`id` = 42	1	1	0
SELECT `County`.`id`, `County`.`county_name`, `County`.`created`, `County`.`modified` FROM `ctr`.`counties` AS `County` WHERE `County`.`id` = 27	1	1	0
SELECT `County`.`id`, `County`.`county_name`, `County`.`created`, `County`.`modified` FROM `ctr`.`counties` AS `County` WHERE `County`.`id` = 47	1	1	0
SELECT `County`.`id`, `County`.`county_name`, `County`.`created`, `County`.`modified` FROM `ctr`.`counties` AS `County` WHERE `County`.`id` = 42	1	1	0
SELECT `County`.`id`, `County`.`county_name`, `County`.`created`, `County`.`modified` FROM `ctr`.`counties` AS `County` WHERE `County`.`id` = 27	1	1	0
SELECT `County`.`id`, `County`.`county_name`, `County`.`created`, `County`.`modified` FROM `ctr`.`counties` AS `County` WHERE `County`.`id` = 47	1	1	0
SELECT `County`.`id`, `County`.`county_name`, `County`.`created`, `County`.`modified` FROM `ctr`.`counties` AS `County` WHERE `County`.`id` = 22	1	1	0
SELECT `County`.`id`, `County`.`county_name`, `County`.`created`, `County`.`modified` FROM `ctr`.`counties` AS `County` WHERE `County`.`id` = 27	1	1	0
SELECT `County`.`id`, `County`.`county_name`, `County`.`created`, `County`.`modified` FROM `ctr`.`counties` AS `County` WHERE `County`.`id` = 42	1	1	0
SELECT `County`.`id`, `County`.`county_name`, `County`.`created`, `County`.`modified` FROM `ctr`.`counties` AS `County` WHERE `County`.`id` = 3	1	1	0
SELECT `County`.`id`, `County`.`county_name`, `County`.`created`, `County`.`modified` FROM `ctr`.`counties` AS `County` WHERE `County`.`id` = 1	1	1	0
SELECT `County`.`id`, `County`.`county_name`, `County`.`created`, `County`.`modified` FROM `ctr`.`counties` AS `County` WHERE `County`.`id` = 47	1	1	0
SELECT `County`.`id`, `County`.`county_name`, `County`.`created`, `County`.`modified` FROM `ctr`.`counties` AS `County` WHERE `County`.`id` = 44	1	1	0
SELECT `Sponsor`.`id`, `Sponsor`.`application_id`, `Sponsor`.`sponsor`, `Sponsor`.`sponsor_type`, `Sponsor`.`contact_person`, `Sponsor`.`address`, `Sponsor`.`telephone_number`, `Sponsor`.`fax_number`, `Sponsor`.`cell_number`, `Sponsor`.`email_address`, `Sponsor`.`created`, `Sponsor`.`modified` FROM `ctr`.`sponsors` AS `Sponsor` WHERE `Sponsor`.`application_id` IN (829, 967, 221, 202, 90)	5	5	1	maybe slow
SELECT COUNT(*) AS `count` FROM `ctr`.`applications` AS `Application` WHERE `Application`.`approved` = 2 AND `Application`.`submitted` = '1' AND `Application`.`deactivated` = '0' AND `Application`.`deleted` = '0'	1	1	4	maybe slow
SELECT `TrialStatus`.`id`, `TrialStatus`.`name` FROM `ctr`.`trial_statuses` AS `TrialStatus` WHERE 1 = 1	9	9	0

6 duplicate queries run.

Query Explain:

Click an "Explain" link above, to see the query explanation.

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Timer

Memory

Peak Memory Use 11.06 MB

Message	Memory use
Component initialization	2.40 MB
Controller action start	3.68 MB
Controller render start	4.82 MB
View render complete	5.31 MB

Timers

Total Request Time: 323 (ms)

Message	Time in ms	Graph
Core Processing (Derived from $_SERVER["REQUEST_TIME"])	25.54
Event: Controller.initialize	0.62
Event: Controller.startup	1.05
Controller action	175.63
Event: Controller.beforeRender	38.51
» Processing toolbar data	38.29
Rendering View	21.86
» Event: View.beforeRender	0.08
» Rendering APP/View/Applications/index.ctp	0.54
» » Rendering APP/View/Elements/google-recommend.ctp	0.14
» Rendering APP/View/Elements/application/public_index.ctp	15.25
» Event: View.afterRender	0.05
» Event: View.beforeLayout	0.05
» Rendering APP/View/Layouts/default.ctp	4.94
» » Rendering APP/View/Elements/google-analytics.ctp	0.17
Event: View.afterLayout	0.00

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Log
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Logs

There were no log entries made this request

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Variables
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View Variables
- trial_statuses(array)
 1Recruiting
 2Not yet recruiting
 3Suspended
 4Stopped
 5Completed
 6In follow-up
 7Analysing
 8Writing-up
 9Application withdrawn
- applications(array)
 0(array)
 Application(array)
 id829
 user_id526
 trial_status_id5
 abstract_of_study\n Worldwide estimates suggest that people living with HIV/AIDS (PLWH) smoke at nearly three times the rate of the general population. Smoking among PLWH living in Sub-Saharan Africa is associated with gender (male>female), with living in an urban slum community, and perhaps most importantly with illicit substance use. Although precise prevalence estimates of tobacco use among PLWH in Kenya are lacking, recent data collected from a large, well established methadone maintenance program in Nairobi found the prevalence of smoking among PLWH with opiate use disorders was 100%. This compares to 7.7-9.1% Kenyan general population. Many interventions are effective in helping smokers in the general population quit. To what degree these data translate to PLWH in lower-middle income countries that may have greater challenges with health infrastructure, resources and medication access, is not clear. Our proposed study will use a factorial design to evaluate the most promising and accessible behavioral and pharmacologic treatments aimed at achieving maximal efficacy for smoking cessation among PLWH who smoke. We propose to randomize 300 participants PLWH, who smoke and who are receiving care in a health care setting program in Nairobi, Kenya to one of the following 4 conditions: (1) bupropioin + Positively Smoke Free (an 8 session tailored behavioral intervention for PLWH smokers); (2) bupropion + Standard of Care (brief advice to quit); (3) Placebo + Positively Smoke Free; and (4) Placebo + Standard of Care. We plan to use a factorial design as it is a highly efficient method of assessing multiple treatments in a single trial with the possibility of saving both time and resources. We plan to conduct the study in methadone maintenance clinics as well as in HIV clinics within Nairobi County. As Kenya has one of the strongest anti-tobacco legislations in sub-Saharan Africa, results of this study will provide policymakers, community leaders and clinicians with critical evidence of the most effective smoking cessation treatments for PLWH smokers in the methadone maintenance setting\n
 study_title\n Optimizing Smoking Cessation Interventions For People Living With Human Immunodeficiency Virus in Nairobi, Kenya\n
 laymans_summary\n This study investigated both pharmacological and behavorial interventions to smoking cessation among participants that are HIV positive and on ART each with a control group. The trial used a factorial design to randomize participants into 4 conditions: (1) bupropion (12 weeks) + PSF (8 weeks) (2) bupropion (12 weeks) + Standard of Care (SOC), i.e., brief advice to quit; (3) Placebo (12 weeks) + PSF (8 weeks); and (4) Placebo (12 weeks) + SOC.\n\n Below is a figure of the results:\n\n <img alt=\"\" src=\"data:image/png;base64,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\" />\n\n \n\n \n
 short_titleSmoking Cessation Study for PLHIV
 protocol_noECCT/19/10/03
 version_no4
 date_of_protocol03-09-2019
 study_drugBupropion
 disease_conditionSmoking Dependance
 product_type_biologicals0
 product_type_proteins0
 product_type_immunologicals0
 product_type_vaccines0
 product_type_hormones0
 product_type_toxoid0
 product_type_chemical1
 product_type_medical_device0
 product_type_chemical_nameBupropion 150
 product_type_medical_device_name
 comparatorYes
 comparator_namePlacebo
 comparator_registered
 comparator_countries
 ecct_not_applicable0
 ecct_ref_number
 email_addressaachie144k@gmail.com
 applicant_covering_letter1
 applicant_protocol1
 applicant_patient_information1
 applicant_investigators_brochure1
 applicant_investigators_cv1
 applicant_signed_declaration1
 applicant_financial_declaration1
 applicant_gmp_certificate1
 applicant_indemnity_cover1
 applicant_opinion_letter1
 applicant_approval_letter1
 applicant_statement1
 applicant_participating_countries0
 applicant_addendum0
 applicant_fees1
 applicant_complete_form(null)
 applicant_impd0
 applicant_prev_data0
 applicant_stability_data0
 applicant_analysis_cert1
 applicant_pictorial_sample1
 applicant_gcp_training1
 applicant_dsmb_charter1
 applicant_detailed_budget1
 applicant_indemnity_pi1
 applicant_practice_license1
 applicant_registration_ctr(null)
 applicant_pan_african1
 applicant_hard_copies(null)
 applicant_signed_checklist1
 statistical_analysis_plan(null)
 applicant_contractual_agreement(null)
 declaration_applicantDr Emily Koech
 declaration_date115-10-2019
 declaration_principal_investigatorDr Sylvia Ojoo
 declaration_date215-10-2019
 placebo_presentYes
 study_objectives<div>\n Primary objectives:</div>\n<div>\n 1. To compare bupropion therapy to placebo on rates of 7-day point prevalence abstinence (PPA) at 36 weeks in smokers with HIV/AIDS. We hypothesize that rates of smoking abstinence at week 36 will be higher in those treated with bupropion compared to placebo.</div>\n<div>\n 2. To compare Positively Smoke Free to low intensity, brief counseling on rates of 7-day PPA at 36 weeks in smokers with HIV/AIDS. We hypothesize that rates of smoking abstinence at week 36 will be higher in those treated with Positively Smoke Free compared to brief counseling.</div>\n<div>\n 3. To compare Positively Smoke Free + bupropion to the other two study conditions outlined above on rates of 7-day PPA in smokers with HIV/AIDS at 36 weeks. We hypothesize the effect of Positively Smoke Free with bupropion therapy is greater than the effect of Positively Smoke Free or bupropion therapy alone.</div>\n<div>\n </div>\n<div>\n </div>\n<div>\n Major Secondary Objectives:</div>\n<div>\n To estimate the organizational costs of implementing Positively Smoke Free, bupropion or both. All cost estimates will be appropriately time-discounted and inflation-adjusted. The planned assessment will yield rigorously obtained approximations of total implementation costs at a new site of care.</div>\n<div>\n </div>\n<div>\n Other Secondary Objectives:</div>\n<div>\n Other objectives of this study are to explore whether the effect of PSF compared to brief counseling with bupropion is greater than the effect of PSF without bupropion.</div>\n
 principal_inclusion_criteria<div>\n Inclusion criteria</div>\n<div>\n 1. Confirmed chart diagnosis of a HIV and receiving HIV treatment at the participating HIV clinic</div>\n<div>\n 2. Age 18 years and older</div>\n<div>\n 3. Currently self-report smoking approximately 10 cigarettes per day.</div>\n<div>\n 4. Motivation to quit (score 5-8 on the Abrams and Briener Readiness to Quit Ladder)</div>\n<div>\n 5. Does not meet criteria for current DSM 5 moderate or severe alcohol use disorder or moderate or</div>\n<div>\n severe substance use disorder as established by the MINI drug and alcohol sections (in the last 3</div>\n<div>\n months)</div>\n<div>\n 6. Able to read and speak English or Swahili</div>\n<div>\n 7. Willingness and ability to provide informed consent to participate</div>\n
 principal_exclusion_criteria<div>\n Exclusion Criteria</div>\n<div>\n 1. Current suicidal thoughts, attempts or ideation (past month); as assessed by the MINI suicidality</div>\n<div>\n section. Score of 1 or higher excludes individuals.</div>\n<div>\n 2. Recent use of Bupropion (by participant report in the past 3 months)</div>\n<div>\n 3. Previous allergic reaction or hypersensitivity to Bupropion (by participant report ever in lifetime)</div>\n<div>\n 4. Pregnant, nursing, or becoming pregnant during the study (pregnancy test)</div>\n<div>\n 5. Current use of any medication that would interfere with the protocol in the opinion of Medically</div>\n<div>\n Accountable Physician including use of bupropion targeting nicotine dependence</div>\n<div>\n 6. Moderate to severe renal impairment (< 30 mL/min)--As determined by a physician assessment,</div>\n<div>\n chart review or thru blood work</div>\n<div>\n 7. Unstable cardiovascular disease (myocardial infarction within past year, uncontrolled arrhythmia,</div>\n<div>\n uncontrolled angina, uncontrolled congestive heart failure, electrocardiogram abnormality with</div>\n<div>\n QTC > 500 msec, cerebrovascular event within past year). (As determined by a physician</div>\n<div>\n assessment, chart review and/or EKG)</div>\n<div>\n 8. Meets criteria for dementia by scoring below 10 on the Hopkins HIV Dementia Scale. This criterion</div>\n<div>\n is included to ensure the sample consists of participants who are cognitively able to engage in the</div>\n<div>\n study procedures</div>\n<div>\n 9. Scores <5 ppm of expired carbon monoxide (CO) on the Smokelyzer</div>\n<div>\n 10. The study physician believes that the individual is not medially stable enough to participate in the</div>\n<div>\n study. This exclusion will be based on a review of the individual's past medical history and current</div>\n<div>\n medical status.</div>\n<div>\n </div>\n
 primary_end_points<div>\n Primary Outcome:</div>\n<div>\n Smoking Abstinence at 12 weeks and 36 weeks)</div>\n<div>\n Abstinence will be based on self-reported 7 point prevalence abstinence (PPA) confirmed by expired CO<7</div>\n<div>\n ppm. Abstinence criteria must be met in study Week 36 or at an earlier study week and maintained through</div>\n<div>\n study Week 36 to be considered a responder. Rationale for 36 week outcome: This was chosen based on</div>\n<div>\n the Society for Research on Nicotine and Tobacco’s Working Group on Abstinence Outcomes Measures19</div>\n<div>\n most recent recommendation.</div>\n<div>\n </div>\n
 scope_diagnosis0
 scope_prophylaxis0
 scope_therapy1
 scope_safety0
 scope_efficacy0
 scope_pharmacokinetic0
 scope_pharmacodynamic0
 scope_bioequivalence0
 scope_dose_response0
 scope_pharmacogenetic0
 scope_pharmacogenomic0
 scope_pharmacoecomomic0
 scope_others1
 scope_others_specifyBehavioral
 trial_human_pharmacology0
 trial_administration_humans0
 trial_bioequivalence_study0
 trial_other0
 trial_other_specify
 trial_therapeutic_exploratory0
 trial_therapeutic_confirmatory0
 trial_therapeutic_use1
 design_controlledYes
 site_capacity(null)
 staff_numbers\n The study will be carried out in collaboration with the Nairobi City County Health Services Division (see letter of support: Appendix A) primarily with patients receiving medical care at the Mathari National Teaching and Referral Hospital (MNTRH). MNTHR is the only dedicated mental health (MH) hospital and MH teaching/referral facility in the country, with affiliations to several universities thus serving as a major agency for health related practices in the country. This 650 bed facility with an onsite pharmacy equipped for research is home to an HIV clinic and a Methadone Assisted treatment (MAT) clinic.\n\n The core Study Staff include the following:\n<div>\n Patience Oduor , Study Coordinator (12.0 cal. months Years 1-5) The Country Study Coordinator will be responsible for overseeing, in conjunction with the Co-Investigator, all daily aspects of the study. She will monitor study recruitment, implementation, data collection and will work with the Investigators, Wendy Potts and local regulatory agencies to ensure compliance with Internal Review Board (IRB) requirements in the field and ensure that data collection and data processes meet quality assurance standards. She will provide local supervision for facility based Study Assessors and Data Entry staff. Working closely with Ms. Potts (who will also serve as the overall Clinic-Study Liaison for each participating site), She will also conduct study assessments as needed, facilitate the meeting and implementation of CAB recommendations, and ensure the timely and quality assured collection and collation of local study data.</div>\n<div>\n </div>\n<div>\n Linda Khakali and Maureen Ondire -Research Assistants (12.0 cal. months Years 1-5) Two locally based Research Assistants will be responsible for performing all study related assessments and interviews at all time points, will schedule assessments and coordinate follow-up visits, code Adherence and Competence ratings as appropriate and assist in data checking and entry. They will provide recruitment at the study sites, arrange visit days and ensure laboratory draws as necessary. They will schedule medication dispensing times and work closely with the pharmacists to ensure appropriate dosing and follow up appointments. They will perform chart reviews as necessary and serve as the primary managers and collators of study related data. They will also work closely with community counselors and the CAB to ensure that study participant concerns and needs are addressed appropriately.</div>\n<div>\n </div>\n<div>\n Dr. Angela Omanya: Study Pharmacist: Dr Omanya is the program pharmacist and has commendable experience establishing and managing methadone and ARV supply chain systems as well as dispensing and inventory management of this at facility level among people who inject drugs. She will work with the protocol development team to ensure compliance with kenya regulatory bodies: Kenya Pharmacy and Poisons Board and support medication management at facility level. She will order supplies, create dispensing labels and logs for the supplies in consultation with the site pharmacist.</div>\n<div>\n </div>\n<div>\n Tina Masai;Study Psychologist: Tina is the lead specialist in structuring the systems for the provision of psychosocial services to patients who suffer from opioid dependence or other drug abuse related behavioral problems. She is responsible for mentorship of Addiction Counselors working in the MAT clinics including patient treatment plans development and re-evaluation and leading group therapy sessions. In this study, she will support in the review of patient materials, conduct of focused group discussions and support patient follow-up activities.</div>\n
 other_details_explanation\n The Positive Smoke Free, PSF, has been successfully studied in the West in similiar settings but no studies have been conducted in a lower income setting such as this.\n
 other_details_regulatory_notapproved\n None\n
 other_details_regulatory_approved\n None\n
 other_details_regulatory_rejected\n None\n
 other_details_regulatory_halted\n None\n
 estimated_durationFive years
 design_controlled_randomisedYes
 design_controlled_openNo
 design_controlled_single_blindNo
 design_controlled_double_blindYes
 design_controlled_parallel_groupNo
 design_controlled_cross_overNo
 design_controlled_otherNo
 design_controlled_specify
 design_controlled_comparator1. Biomedical-Bupropion/P
 design_controlled_other_medicinalNo
 design_controlled_placeboYes
 design_controlled_medicinal_otherNo
 design_controlled_medicinal_specify
 single_site_member_stateYes
 location_of_areaMathari National Teaching and Referral Hospital
 single_site_physical_addressMuthaiga, Along Thika Super Highway
 single_site_contact_personPatience Oduor
 single_site_telephone0780445855
 multiple_sites_member_stateNo
 multiple_countriesNo
 multiple_member_states
 number_of_sites
 multi_country_list
 data_monitoring_committeeYes
 total_enrolment_per_site300
 total_participants_worldwide300
 population_less_than_18_yearsNo
 population_uteroNo
 population_preterm_newbornNo
 population_newbornNo
 population_infant_and_toddlerNo
 population_childrenNo
 population_adolescentNo
 population_above_18Yes
 population_adultYes
 population_elderlyYes
 gender_female1
 gender_male1
 subjects_healthyYes
 subjects_patientsYes
 subjects_vulnerable_populationsYes
 subjects_women_child_bearingYes
 subjects_women_using_contraceptionYes
 subjects_pregnant_womenNo
 subjects_nursing_womenNo
 subjects_emergency_situationNo
 subjects_incapable_consentNo
 subjects_specify
 subjects_othersNo
 subjects_others_specify
 investigator1_given_nameDr. Emily Koech
 investigator1_middle_name
 investigator1_family_nameEmily Koech - Keter
 investigator1_qualificationCountry Director
 investigator1_professional_address495-00606
 investigator1_telephone0735100183
 investigator1_emailekoech@mgic.umaryland.edu
 organisations_transferred_Yes
 number_participants300
 notification\n Find the PSF workbooks on the links below, they were too bulky to be uploaded:\n\n English:<a href=\"https://drive.google.com/file/d/160ouud96ktLHTrVJdWiBTqEQXQwoV7Ud/view\">https://drive.google.com/file/d/160ouud96ktLHTrVJdWiBTqEQXQwoV7Ud/view</a>\n\n Swahili:<a href=\"https://drive.google.com/file/d/1TUc_txhW5QTdH0I-NZPbpvaJgCYHAxxP/view\">https://drive.google.com/file/d/1TUc_txhW5QTdH0I-NZPbpvaJgCYHAxxP/view</a>\n\n We look forward to your feedback and advice.\n
 approval_date03-04-2020
 submitted1
 deleted0
 deleted_date(null)
 deactivated0
 date_submitted03-04-2020
 is_child0
 unsubmitted0
 initial_date_submitted(null)
 admin_stopped0
 admin_stopped_reason(null)
 approved2
 approved_reasonStudy approved by PPB ECCT
 final_report\n Worldwide estimates indicate that people with HIV smoke at much higher rates than the general population resulting in higher risk for tobacco related morbidity and mortality. The efficacy of smoking cessation interventions among people with HIV in lower-middle income countries remains unclear. We conducted a randomized, 2x2 factorial design trial based in Nairobi, Kenya, to evaluate the efficacy of bupropion vs. placebo, and a culturally-tailored, behavioral cessation therapy, Positively Smoke Free (PSF), vs. standard of care (SOC) for people with HIV and smoked as well. The primary outcome was 7-day point prevalence abstinence confirmed by exhaled carbon monoxide <7ppm at 36 weeks.\n\n Between June 2020 and August 2023, 300 participants were randomized. Most participants were men (71.4%) who were moderately dependent on nicotine; nearly all (99.7%) were taking antiretroviral medication. At 36 weeks, 31.3% of participants who received bupropion were abstinent from smoking compared with 13.3% in the placebo group (OR, 2.95; 95% CI, 1.64-5.32, P<0.001). Among participants randomized to receive PSF therapy, 29.5% were abstinent from smoking compared to 14.9% in the SOC group (OR, 2.39; 95% CI, 1.34-4.25, P=0.003). The combination of bupropion + PSF was superior to either bupropion (38.9% vs 20.3%; OR, 2.50; 95% CI, 1.20-5.24; p=0.015) or PSF (38.9% vs 23.6%; OR, 2.06; 95% CI, 1.00-4.23; p=0.049) alone. Both bupropion and PSF cessation counseling were effective in promoting abstinence at 36-weeks. Combined intervention was superior to either alone.\n\n \n
 implication_results\n Zyban, Bupropion HCL, which is currently registered in Kenya for smoking cessation and also in the national formulary can further be used to augment treatment options for persons with nicotine addiction. Due to the cost and availabilty, a generic brand may be registered in country to facilitate non-nicotine replacement therapy regimens as treatment options. \n\n Another success of our findings shows that targetted intensive counselling sessions also greatly aids in the overall outcome of abstinence. Addiction counsellors, medical social workers and clinical staff especially in the mental health doceket can be trained to give such sessions to their patients to optimize treatment along medications given to combat cravings and withdrawals symptoms.\n
 quantity_imported58,950 tablets (30150 placebo and 28800 Zyban, 9000 locally bought and 19800 imported)
 quantity_dispensed57,600 tablets
 quantity_destroyed1528 tablets (1144 placebo and 384 Zyban) this includes returns and buffer pills in patient packs.
 quantity_exported0
 balance_site0
 final_date0000-00-00
 modified2024-09-30 13:07:14
 created2019-10-15 10:32:41
 total_sites(null)
 ecitizen_invoice(null)
 InvestigatorContact(array)
 0(array)
 id512
 application_id829
 given_nameDr. Seth Scott Himelhoch
 middle_name
 family_nameSeth Scott Himelhoch
 qualificationPsychiatrist
 professional_addressDepartment of Psychiatry 245 Fountain Court,Lexington, Kentucky 40509
 telephone(859)257-9015
 emailseth.himelhock@uky.edu
 created2019-10-15 10:37:54
 modified2020-04-03 13:21:46
 SiteDetail(array)
 0(array)
 id671
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 misc(null)
 created2019-10-15 10:37:54
 modified2020-04-03 13:21:46
 County(empty)
 Sponsor(array)
 0(array)
 id400
 application_id829
 sponsorNational Institute of Health (NIH)
 sponsor_typeResearch Institution
 contact_personMark Parascandola, PhD, MPH
 address6701 Rockledge Drive Room 1040-MSC 7710 Bethesda,MD 20892
 telephone_number+4436048648
 fax_number
 cell_number+4436048648
 email_addressparamark@mail.nih.gov
 created2019-10-15 10:37:54
 modified2020-04-03 13:21:46
 1(array)
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 abstract_of_study\n Severely malnourished children who present with an acute illness have a high risk of mortality. Severe malnutrition is associated with intestinal inflammation and changes in the faecal microbiome (‘dysbiosis’). Apart from the large intestine, this dysbiosis is also present in the small intestine, where increased bacterial density and altered microbial composition can contribute to intestinal inflammation and intestinal dysfunction which may ultimately contribute to the development of sepsis and death. The bacterial density and composition in the small intestine can be reduced and altered, respectively, using antibiotics. However, apart from side effects, antibiotic use contributes to the development of antibiotic resistance, which is very common in hospitalized malnourished patients and can pose a threat to both individual and public health. In addition to intestinal dysbiosis and intestinal inflammation, children with severe malnutrition suffer from impaired exocrine pancreatic and hepatobiliary function, which are important for nutrient digestion and absorption. We recently reported that treating children with severe malnutrition with pancreatic enzymes led to a reduction in mortality in a pilot trial which was not powered for mortality. Importantly, enzymes and bile acids produced by the pancreas and liver affect bacteria that reside in the intestinal lumen. We hypothesize that providing these enzymes exogenously to severely malnourished children will improve their clinical outcome by reducing dysbiosis, intestinal inflammation and sepsis. \n \n The objective of this study is to determine whether treating ill severely malnourished children with pancreatic enzymes or bile acids, in addition to standard therapies including empiric antibiotics, improves mortality. We will conduct a double blind, randomized clinical trial in a 2x2 factorial design in hospitalized severely malnourished children. We will treat participants with paediatric formulations of pancreatic enzymes, bile acids, both or placebo for 21 days. Participants will be followed up daily during their hospital stay, and on day 21 and 60 after enrolment. We will conduct this trial in three stages to allow for careful interim evaluations to assess safety and study progress. In the first and second stage, we will conduct interim analyses to assess safety and likelihood of benefit before enrolling the full sample size to assess mortality as the primary outcome. Secondary outcomes include adverse events, length of hospital stay, and growth. Exploratory outcomes will examine intestinal and systemic inflammation and metabolic changes to examine mechanisms affected by the interventions, and costs. Two sub-studies will also be conducted. In Kenya and Bangladesh, a substudy examining daily blood gases, lactate and biochemistry during the first 5 days of enrolment to assess early clinical progress will be performed. In Malawi and Uganda, hydrogen breath testing performed within 72hr of enrolment and on day 21 following enrolment, will be used to evaluate impact of the intervention on upper small intestinal bacterial overgrowth. \n \n Overall, this trial will determine whether a non-antibiotic, bactericidal intervention given in additional to standard of care management reduces mortality in acutely ill severely malnourished children. \n \n \n
 study_title\n Pancreatic Enzymes and Bile Acids: A Non-Antibiotic approach to Treat Intestinal Dysbiosis in Acutely Ill Severely Malnourished Children.\n
 laymans_summary\n Lay Title \n Controlling intestinal bacteria in sick children with malnutrition. \n \n What is the problem? \n Children with severe malnutrition who are sick and admitted to hospitals have high mortality, usually because of infection. Malnourished children have more potentially harmful bacteria in their upper intestines than well-nourished children and this may contribute to inflammation in the gut and whole body. These bacteria may cross from the intestines to the bloodstream causing life-threatening infection. Another abnormality among malnourished children is reduction in the digestive enzymes made by the pancreas and the liver. Apart from helping with digestion of food, these enzymes are important in controlling bacteria in the intestines. It is therefore possible that treatment with digestive enzymes could help reduce the burden of harmful bacteria and thus lower inflammation and risk of serious infection. One study conducted in Malawi has shown that children with severe malnutrition who were supplemented with pancreatic enzymes had a lower risk of dying. However, this was a small study and although promising, requires validation. No studies of supplementation with bile acids have been done among severely malnourished children. However, bile acids are commonly used to manage patients with cholestatic liver diseases, something that malnourished children suffer from as well. \n \n What questions are we trying to answer? \n We want to find out if giving special salts, which are enzymes that help in digestion (pancreatic enzymes and bile acids), in addition to the standard of care, for ill children with severe acute malnutrition is safe and reduces the risk of death, deterioration or readmission to hospital. We will also assess the costs associated with the interventions to patients and health providers. \n \n \n Where is the study taking place, how many people does it involve and how are they selected? \n The study is being carried out by the CHAIN Network (www.chainnetwork.org) a network of doctors and scientists committed to improving the lives of sick and undernourished children. We will carry out the study in hospitals in Kenya, Malawi, Uganda and Bangladesh that are CHAIN Network sites. We will ask parents and guardians of children between the ages of 2 months to 59 months who are admitted to hospital with severe malnutrition and clinical signs of severe illness to participate. \n \n The trial will be conducted in 3 stages. In the first stage, we will enrol 200 children with severe malnutrition admitted to hospital with severe illness across all sites. This will be followed by an interim analysis focused on confirming safety. Then which a further 200 children across all sites will be enrolled in stage 2. A second interim analysis will then be done and if the study results suggest one or both interventions are safe and potentially effective, then a further 800 children across all sites will be enrolled in the third stage resulting in a total of 1,200 children enrolled. \n \n What does the study involve for those who are in it? \n After obtaining informed consent, a study clinician will examine the child and the special salts that help in digestion or similar looking placebo products without active ingredients will be randomly allocated. Children will receive the study medications by mouth or nasogastric tube (if an NG tube is sited for feeding) before feeds for 21 days (both in hospital and at home if discharged early) and will be followed up at 21 and 60 days from enrolment. Pancreatic enzymes are in form of powdered granules which will be given by sprinkling over normal food or with therapeutic milk feeds. Bile acids are in form of oral syrup. In addition to the study medication(s) and/or placebo, all children enrolled in the study will also receive the standard treatments for severe malnutrition (for example, empiric antibiotics), as provided by the local admitting hospital. \n \n 3 ml of blood (about half a tablespoon), rectal swabs, and a faecal sample will be taken together with the routine tests for care at enrolment to the trial, then at 21 days after enrolment. Blood sample for research will not exceed 1ml/kg while total volume collected at enrolment will vary according to tests required at admission. Rectal swabs and a faecal sample will also be collected at hospital discharge and at 60 days after enrolment. In addition, Kilifi participants will have a finger-prick blood sample taken once each day for 5 days after enrolment to measure salts, oxygen and lactate in the child’s blood as they continue to receive treatment. If blood for routine care tests is being taken, then a drop will be used instead of a finger-prick. \n \n Children will be reviewed daily by the study team while in hospital. Study staff will work together with hospital staff to provide the highest quality of care available to all children. Follow up visits will involve a health questionnaire, measuring growth and the collection of rectal swabs (D21 and D60), a faecal sample (D21 and D60), and a 3ml blood sample (D21 only). Parents will be advised to contact the study team and bring the child to the hospital if he/she becomes unwell. If readmitted, 3ml of blood (about half a tablespoon), rectal swabs, and a faecal sample will be taken with routine tests for research. All results of blood tests that are available in real-time will be fed back to the clinical team to assist in care. Some parents, caregivers and health providers will also be interviewed about costs incurred for treatment. \n \n What are the benefits and risks/costs of the study for those involved? \n Training and staffing will be enhanced for all paediatric ward staff on the treatment of sick and malnourished children. The sites involved are already in the CHAIN Network which has standardised care according to World Health Organisation and National guidelines and has ongoing monitoring of care. Pancreatic enzymes and bile acids have a good safety profile. However, any evidence of harm will be carefully assessed, and appropriate management provided. Drawing a blood sample carries risks of discomfort and damage to the vein or infection; careful procedures including cleaning the skin will help prevent these. Performance of rectal swabs and faeces collection entails minimal risk. Travel costs and out of pocket allowances associated with scheduled follow up visits will be reimbursed according to local institutional policies. \n During the study, appropriate precautions will be taken to protect participants and staff from COVID-19 infection through training and provision of personal protective equipment and hand sanitisation facilities. Participants’ carers will be given surgical facemasks and appropriate hand hygiene. Where possible, face to face contact and home visits will be minimised according to local institutional procedures. \n \n How will the study benefit society? \n Knowing how to better treat ill malnourished children when they are admitted to hospital will help inform the development of optimal interventions to improve child health and survival. The findings from this research will directly inform policy and program management decisions related to the care of the sick child. \n \n When does the study start and finish? \n The study aims to start as soon as scientific and ethical approval is granted and the COVID-19 pandemic situation permits research to take place. We will undertake two interim analyses after 200 then 400 participants (expected after about 1 to 1.5 years) to assess safety and the likelihood of effectiveness before enrolling the full sample size. One or both study medications may be discontinued at these interim analyses if they are unlikely to be of benefit, or the final sample size may be adjusted if needed. The trial will require approximately 3 to 4 years of enrolment and 5 years to complete from the start to the end of analysis. \n \n \n
 short_titlePB-SAM
 protocol_noECCT/21/03/02
 version_no1.1
 date_of_protocol11-01-2021
 study_drugPancreatic enzymes and Ursodeoxycholic acid (bile acid)
 disease_conditioncomplicated severe acute malnutrition
 product_type_biologicals0
 product_type_proteins0
 product_type_immunologicals0
 product_type_vaccines0
 product_type_hormones0
 product_type_toxoid0
 product_type_chemical1
 product_type_medical_device0
 product_type_chemical_namePancreatic enzymes and Ursodeoxycholic acid (bile acid)
 product_type_medical_device_name
 comparatorNo
 comparator_name
 comparator_registered
 comparator_countries
 ecct_not_applicable0
 ecct_ref_number
 email_addressCGMRCCSC@kemri-wellcome.org
 applicant_covering_letter1
 applicant_protocol1
 applicant_patient_information1
 applicant_investigators_brochure1
 applicant_investigators_cv1
 applicant_signed_declaration1
 applicant_financial_declaration1
 applicant_gmp_certificate1
 applicant_indemnity_cover1
 applicant_opinion_letter1
 applicant_approval_letter0
 applicant_statement1
 applicant_participating_countries(null)
 applicant_addendum1
 applicant_fees1
 applicant_complete_form(null)
 applicant_impd1
 applicant_prev_data1
 applicant_stability_data1
 applicant_analysis_cert1
 applicant_pictorial_sample1
 applicant_gcp_training1
 applicant_dsmb_charter1
 applicant_detailed_budget1
 applicant_indemnity_pi1
 applicant_practice_license1
 applicant_registration_ctr(null)
 applicant_pan_african1
 applicant_hard_copies(null)
 applicant_signed_checklist1
 statistical_analysis_plan1
 applicant_contractual_agreement1
 declaration_applicantIsaiah Njagi
 declaration_date116-03-2021
 declaration_principal_investigatorCaroline Ogwang (Clinical lead)
 declaration_date216-03-2021
 placebo_presentYes
 study_objectives\n \n Primary objective \n To determine whether treatment with pancreatic enzymes or bile acids reduce mortality in acutely ill hospitalized children with severe malnutrition compared to placebo. \n \n Secondary objectives \n To determine: \n 1. Rate and type of SAEs (including readmissions to hospital) \n 2. Safety: rate of grade 3 or 4 toxicity events whilst receiving investigational products \n 3. Intestinal function: number of days with diarrhoea during admission. \n 4. Use of second and third-line antibiotics during admission and readmission \n 5. Number of days from enrolment to discharge during admission \n 6. Growth: (MUAC, weight-for-length, length-for-age) to day 60. \n \n \n
 principal_inclusion_criteria\n • Age ≥2 to <59 months \n • Admitted to hospital with an acute, non-traumatic illness and within 72 hours of admission at the time of enrolment \n • Severe malnutrition (weight-for-height <-3 z scores of the median WHO growth standards and/or mid upper arm circumference <115mm (<110mm age below 6 months), or symmetrical oedema of at least the feet related to malnutrition (not related to a primary cardiac or renal disorder) \n • Presence of two or more features of severity as specified in Table 4 below. If a child meets two criteria, they may be enrolled before further criteria are assessed (e.g. a child may be eligible on clinical signs before the complete blood count results are known). \n • Accompanied by care provider who provides written informed consent \n • Primary caregiver plans to stay in the study area during the duration of the study. \n \n \n
 principal_exclusion_criteria\n • Requires immediate cardiac/respiratory resuscitation (may be re-evaluated for study eligibility within 72h of admission) \n • Presence of terminal illness (other than severe acute malnutrition) likely to result in death within 6 months in the opinion of the recruitment team \n • Known congenital heart disease \n • Admission for traumatic or surgical indication \n • Known liver disorder or exocrine pancreatic disorder – e.g. biliary atresia, history of gallstones, cystic fibrosis or clinical jaundice \n • Known stomach or duodenal ulcer \n • Residence is outside the catchment area of study hospital \n • Primary caregiver declines to provide informed consent \n • Known intolerance or allergy to any study medication \n \n \n
 primary_end_points\n The primary endpoint for the trial for both interventions is mortality. This will be assessed from study enrolment through day 60 of follow up.\n
 scope_diagnosis0
 scope_prophylaxis0
 scope_therapy1
 scope_safety1
 scope_efficacy1
 scope_pharmacokinetic0
 scope_pharmacodynamic0
 scope_bioequivalence0
 scope_dose_response0
 scope_pharmacogenetic0
 scope_pharmacogenomic0
 scope_pharmacoecomomic0
 scope_others0
 scope_others_specify
 trial_human_pharmacology0
 trial_administration_humans0
 trial_bioequivalence_study0
 trial_other1
 trial_other_specifyNew indication (Intestinal dysbiosis), new population (acutely ill severely malnourished children)
 trial_therapeutic_exploratory0
 trial_therapeutic_confirmatory1
 trial_therapeutic_use0
 design_controlledYes
 site_capacity(null)
 staff_numbers<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:654px;\" width=\"654\">\n <tbody>\n <tr>\n <td colspan=\"4\" style=\"width:654px;height:23px;\">\n \n Kilifi\n \n \n \n Staffing\n </td>\n </tr>\n <tr>\n <td style=\"width:144px;height:8px;\">\n \n Staff\n </td>\n <td style=\"width:139px;height:8px;\">\n \n Names\n </td>\n <td style=\"width:131px;height:8px;\">\n \n Qualifications\n </td>\n <td style=\"width:240px;height:8px;\">\n \n Experience\n </td>\n </tr>\n <tr>\n <td style=\"width:144px;height:17px;\">\n \n Clinical Investigator (1)\n </td>\n <td style=\"width:139px;height:17px;\">\n \n Caroline Ogwang\n </td>\n <td style=\"width:131px;height:17px;\">\n \n MBChB, Msc Epidemiology\n </td>\n <td style=\"width:240px;height:17px;\">\n \n Clinical Trial experience, site management\n </td>\n </tr>\n <tr>\n <td rowspan=\"4\" style=\"width:144px;height:23px;\">\n \n Clinicians (n=4)\n </td>\n <td style=\"width:139px;height:23px;\">\n \n Shalton Mwaringa\n </td>\n <td style=\"width:131px;height:23px;\">\n \n HND – Clinical Medicine (Paediatrics)\n </td>\n <td style=\"width:240px;height:23px;\">\n \n Clinical Trials, data collection, site management\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:16px;\">\n \n Grace Dena\n </td>\n <td style=\"width:131px;height:16px;\">\n \n Dip. Clinical Medicine\n </td>\n <td style=\"width:240px;height:16px;\">\n \n Clinical Trials, data collection\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:16px;\">\n \n Alexander Makazi\n </td>\n <td style=\"width:131px;height:16px;\">\n \n HND – Clinical Medicine (Paediatrics)\n </td>\n <td style=\"width:240px;height:16px;\">\n \n Clinical Trials, data collection\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:16px;\">\n \n John Paul Odhiambo\n </td>\n <td style=\"width:131px;height:16px;\">\n \n Dip. Clinical Medicine\n </td>\n <td style=\"width:240px;height:16px;\">\n \n Clinical Trials, data collection\n </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:144px;height:7px;\">\n \n Nurses (2)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Joy Lewa\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Bsc. Nursing\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Clinical trials, drug admin and management\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Riziki Ahmed\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Dip. Nursing\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Clinical trials, drug admin and management\n </td>\n </tr>\n <tr>\n <td rowspan=\"6\" style=\"width:144px;height:7px;\">\n \n Field Workers (6)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Mwanajuma Juma\n </td>\n <td style=\"width:131px;height:7px;\">\n \n O-Level\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data collection, field work, data entry\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Kahindi Charo\n </td>\n <td style=\"width:131px;height:7px;\">\n \n O-Level\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data collection, field work\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Janet Lozi\n </td>\n <td style=\"width:131px;height:7px;\">\n \n O-Level\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data collection, field work\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Nichodemus Wara\n </td>\n <td style=\"width:131px;height:7px;\">\n \n O-Level\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data collection, field work, data entry\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Margaret Nyevu\n </td>\n <td style=\"width:131px;height:7px;\">\n \n O-Level\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data collection, field work, data entry\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Agnes Kavumbi\n </td>\n <td style=\"width:131px;height:7px;\">\n \n O-Level\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data collection, field work\n </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:144px;height:7px;\">\n \n Lab technologist (2)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Robert Musyimi\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Dip. Lab technology\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Microbiology, AST testing, biorepository\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Edwin Machanja\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Dip. Lab technology\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Microbiology, AST testing, biorepository\n </td>\n </tr>\n <tr>\n <td style=\"width:144px;height:7px;\">\n \n Senior Data Supervisor (1)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Amos Fondo\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Bsc. Computer Science\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data entry, data cleaning, query management\n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:654px;height:7px;\">\n \n Site Facilities\n <ul>\n <li>\n Office space with adequate resources i.e. furniture, internet connectivity and computers</li>\n <li>\n Access to programme transport for community follow up</li>\n <li>\n Laboratory network – Full microbiology, hematology, parasitology and immunology</li>\n <li>\n Kilifi County Hospital: Paediatric ward, acute room, maternal and child health clinic, paediatric outpatient clinic</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:654px;height:7px;\">\n \n Emergency facilities\n <ul>\n <li>\n Access to the High Dependency Unit (HDU) in Kilifi County Hospital</li>\n </ul>\n \n \n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:654px;height:7px;\">\n \n Other Infrastructure\n <ul>\n <li>\n Demographic surveillance System (DSS)</li>\n <li>\n Bio-banking</li>\n <li>\n Community Liaison Department</li>\n <li>\n Access to hospital paediatric consultants and other county health staff.</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:673px;\" width=\"673\">\n <tbody>\n <tr>\n <td colspan=\"4\" style=\"width:673px;height:29px;\">\n \n Mombasa\n \n \n \n Staffing\n </td>\n </tr>\n <tr>\n <td style=\"width:144px;height:8px;\">\n \n Staff\n </td>\n <td style=\"width:139px;height:8px;\">\n \n Names\n </td>\n <td style=\"width:144px;height:8px;\">\n \n Qualifications\n </td>\n <td style=\"width:246px;height:8px;\">\n \n Experience\n </td>\n </tr>\n <tr>\n <td style=\"width:144px;height:17px;\">\n \n Clinical Investigator (1)\n </td>\n <td style=\"width:139px;height:17px;\">\n \n Caroline Ogwang\n </td>\n <td style=\"width:144px;height:17px;\">\n \n MBChB, Msc Epidemiology\n </td>\n <td style=\"width:246px;height:17px;\">\n \n Clinical Trial experience, site management\n </td>\n </tr>\n <tr>\n <td rowspan=\"3\" style=\"width:144px;height:23px;\">\n \n Clinicians (n=3)\n </td>\n <td style=\"width:139px;height:23px;\">\n \n Laura Mwalekwa\n </td>\n <td style=\"width:144px;height:23px;\">\n \n HND – Clinical Medicine (Paediatrics)\n </td>\n <td style=\"width:246px;height:23px;\">\n \n Clinical Trials, data collection, site management\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:16px;\">\n \n Charity Muli\n </td>\n <td style=\"width:144px;height:16px;\">\n \n Dip. Clinical Medicine\n </td>\n <td style=\"width:246px;height:16px;\">\n \n Clinical Trials, data collection\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:16px;\">\n \n Fauzat Hamid\n </td>\n <td style=\"width:144px;height:16px;\">\n \n Dip. Clinical Medicine\n </td>\n <td style=\"width:246px;height:16px;\">\n \n Clinical Trials, data collection\n </td>\n </tr>\n <tr>\n <td rowspan=\"10\" style=\"width:144px;height:7px;\">\n \n Nurses (10 on locums)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Esther Wangai Njue\n </td>\n <td style=\"width:144px;height:7px;\">\n \n Dip. Nursing,\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Clinical trials, drug administration, rota administration and management\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Beatrice Kithendu\n </td>\n <td style=\"width:144px;height:7px;\">\n \n Dip. Nursing,\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Clinical trials, drug administration,\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Mariam Mohamed\n </td>\n <td style=\"width:144px;height:7px;\">\n \n Dip. Nursing,\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Clinical trials, drug administration\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Maimuna Jeruto Ali\n </td>\n <td style=\"width:144px;height:7px;\">\n \n Dip. Nursing,\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Clinical trials, drug administration\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Roseline M. Masika\n </td>\n <td style=\"width:144px;height:7px;\">\n \n Dip. Nursing,\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Clinical trials, drug administration\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Teresa M. Ndegwa\n </td>\n <td style=\"width:144px;height:7px;\">\n \n Dip. Nursing,\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Clinical trials, drug administration\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Peace Mangale\n </td>\n <td style=\"width:144px;height:7px;\">\n \n Dip. Nursing,\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Clinical trials, drug administration\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Martha Wanje\n </td>\n <td style=\"width:144px;height:7px;\">\n \n Dip. Nursing,\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Clinical trials, drug administration\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Elizabeth Wanza Nyilu\n </td>\n <td style=\"width:144px;height:7px;\">\n \n Dip. Nursing,\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Clinical trials, drug administration\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Betty M. Mwasaru\n </td>\n <td style=\"width:144px;height:7px;\">\n \n Dip. Nursing,\n </td>\n <td style=\"width:246px;height:7px;\">\n \n \n </td>\n </tr>\n <tr>\n <td rowspan=\"5\" style=\"width:144px;height:7px;\">\n \n Field Workers (5)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Anne Ochola\n </td>\n <td style=\"width:144px;height:7px;\">\n \n BSC. Community development\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Data collection, field work, data entry\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Jane Maere\n </td>\n <td style=\"width:144px;height:7px;\">\n \n O-Level\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Data collection, field work\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Grace Wechuli\n </td>\n <td style=\"width:144px;height:7px;\">\n \n O-Level\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Data collection, field work\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Anderson Lewa\n </td>\n <td style=\"width:144px;height:7px;\">\n \n O-Level\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Data collection, field work, data entry\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Silus Haro\n </td>\n <td style=\"width:144px;height:7px;\">\n \n O-Level\n </td>\n <td style=\"width:246px;height:7px;\">\n \n Data collection, field work, data entry\n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:673px;height:7px;\">\n \n Site Facilities\n <ul>\n <li>\n Office space with adequate resources i.e. furniture, internet connectivity and computers</li>\n <li>\n Access to programme transport for community follow up</li>\n <li>\n Outsourced University of Washington laboratory</li>\n <li>\n Coast General Hospital: Paediatric ward, maternal and child health clinic, paediatric outpatient clinic</li>\n </ul>\n \n \n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:673px;height:7px;\">\n \n Emergency facilities\n <ul>\n <li>\n Access to Coast General Hospital Intensive Care Unit</li>\n </ul>\n \n \n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:673px;height:7px;\">\n \n Other Infrastructure\n <ul>\n <li>\n Outsourced university of Washington regional laboratory</li>\n <li>\n Access to hospital paediatric consultants and other county health staff.</li>\n </ul>\n \n \n </td>\n </tr>\n </tbody>\n</table>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:654px;\" width=\"654\">\n <tbody>\n <tr>\n <td colspan=\"4\" style=\"width:654px;height:29px;\">\n \n Mbagathi\n \n \n <ol>\n <li>\n Staffing</li>\n </ol>\n </td>\n </tr>\n <tr>\n <td style=\"width:144px;height:8px;\">\n \n Staff\n </td>\n <td style=\"width:139px;height:8px;\">\n \n Names\n </td>\n <td style=\"width:131px;height:8px;\">\n \n Qualifications\n </td>\n <td style=\"width:240px;height:8px;\">\n \n Experience\n </td>\n </tr>\n <tr>\n <td style=\"width:144px;height:17px;\">\n \n Clinical Investigator (1)\n </td>\n <td style=\"width:139px;height:17px;\">\n \n Caroline Ogwang\n </td>\n <td style=\"width:131px;height:17px;\">\n \n MBChB, Msc Epidemiology\n </td>\n <td style=\"width:240px;height:17px;\">\n \n Clinical Trial experience, site management\n </td>\n </tr>\n <tr>\n <td rowspan=\"3\" style=\"width:144px;height:23px;\">\n \n Clinicians (n=3)\n </td>\n <td style=\"width:139px;height:23px;\">\n \n Molly Timbwa\n </td>\n <td style=\"width:131px;height:23px;\">\n \n HND – Clinical Medicine (Paediatrics), BSc Community health and development\n </td>\n <td style=\"width:240px;height:23px;\">\n \n Clinical Trials, data collection, site management\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:16px;\">\n \n Issack Yerrow\n </td>\n <td style=\"width:131px;height:16px;\">\n \n Dip. Clinical Medicine, BSc Environmental Health\n </td>\n <td style=\"width:240px;height:16px;\">\n \n Clinical Trials, data collection\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:16px;\">\n \n Joshua Wambua\n </td>\n <td style=\"width:131px;height:16px;\">\n \n Dip. Clinical Medicine\n </td>\n <td style=\"width:240px;height:16px;\">\n \n Clinical Trials, data collection\n </td>\n </tr>\n <tr>\n <td style=\"width:144px;height:7px;\">\n \n Nurses (1)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Lilian Kasaya\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Dip. Nursing\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Clinical trials, drug admin and management\n </td>\n </tr>\n <tr>\n <td rowspan=\"5\" style=\"width:144px;height:7px;\">\n \n Field Workers (6)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Karen Kendi\n </td>\n <td style=\"width:131px;height:7px;\">\n \n O-Level\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data collection, field work, data entry\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Elizabeth Weya\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Dip. in Community Health & Development\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data collection, field work\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Jeniffer Mikusa\n </td>\n <td style=\"width:131px;height:7px;\">\n \n O-Level\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data collection, field work\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Anne Mbugua\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Dip. in Community Health and HIV testing\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data collection, field work, data entry\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Charity Magawi\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Dip. in Business Administration\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data collection, field work, data entry\n </td>\n </tr>\n <tr>\n <td style=\"width:144px;height:7px;\">\n \n Lab technologist (1)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Anthony Mwema\n </td>\n <td style=\"width:131px;height:7px;\">\n \n BSc Medical Laboratory,\n \n Dip in Medical Lab Sciences\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Microbiology, AST testing, biorepository\n </td>\n </tr>\n <tr>\n <td style=\"width:144px;height:7px;\">\n \n Data supervisor (1)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Don Obote\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Dip. in Business Administration\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data entry, data query management\n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:654px;height:7px;\">\n \n Site Facilities\n <ul>\n <li>\n Office space with adequate resources i.e. furniture, internet connectivity and computers</li>\n <li>\n Access to programme transport for community follow up</li>\n <li>\n Laboratory network – Hospital lab, Center for Microbiology research labs, and Lancet laboratories</li>\n <li>\n Mbagathi hospital: Paediatric ward, acute room, maternal and child health clinic, paediatric outpatient clinic</li>\n </ul>\n \n \n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:654px;height:7px;\">\n \n Emergency facilities\n <ul>\n <li>\n Access to Kenyatta National Hospital (KNH) Intensive Care Unit (ICU)</li>\n </ul>\n \n \n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:654px;height:7px;\">\n \n Other Infrastructure\n <ul>\n <li>\n Access to biobank in CMR</li>\n <li>\n Access to Regional referral Hospital (KNH)</li>\n <li>\n Work in liaison with Mbagathi hospital paediatric consultants and other county health staff.</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:654px;\" width=\"654\">\n <tbody>\n <tr>\n <td colspan=\"4\" style=\"width:654px;height:29px;\">\n \n Migori\n \n \n \n Staffing\n </td>\n </tr>\n <tr>\n <td style=\"width:144px;height:8px;\">\n \n Staff\n </td>\n <td style=\"width:139px;height:8px;\">\n \n Names\n </td>\n <td style=\"width:131px;height:8px;\">\n \n Qualifications\n </td>\n <td style=\"width:240px;height:8px;\">\n \n Experience\n </td>\n </tr>\n <tr>\n <td style=\"width:144px;height:17px;\">\n \n Clinical Investigator (1)\n </td>\n <td style=\"width:139px;height:17px;\">\n \n \n </td>\n <td style=\"width:131px;height:17px;\">\n \n \n </td>\n <td style=\"width:240px;height:17px;\">\n \n \n </td>\n </tr>\n <tr>\n <td rowspan=\"3\" style=\"width:144px;height:23px;\">\n \n Clinicians (3)\n </td>\n <td style=\"width:139px;height:23px;\">\n \n Chrisantus Oduol\n </td>\n <td style=\"width:131px;height:23px;\">\n \n Diploma in clinical medicine\n </td>\n <td style=\"width:240px;height:23px;\">\n \n Data entry, Qualitative and quantitative data Collection\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:16px;\">\n \n Billy Obware\n </td>\n <td style=\"width:131px;height:16px;\">\n \n Diploma in clinical medicine\n </td>\n <td style=\"width:240px;height:16px;\">\n \n Data entry Qualitative and quantitative data Collection\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:16px;\">\n \n Linet Simiyu\n </td>\n <td style=\"width:131px;height:16px;\">\n \n Diploma in clinical medicine\n </td>\n <td style=\"width:240px;height:16px;\">\n \n Data entry Qualitative and quantitative data Collection.\n </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:144px;height:7px;\">\n \n Field Workers (2)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Victor Ochuodho\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Certificate in Social work and community development\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data collection, entry, field work\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Rubby Owino\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Diploma in community Health and Development\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data collection, entry Biorepository and CBC testing field work\n </td>\n </tr>\n <tr>\n <td style=\"width:144px;height:7px;\">\n \n Nutritionist (1)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Phlona Amam\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Diploma in Nutrition and Dietetics\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Nutrition counselling and case management, anthropometric measurements, data entry.\n </td>\n </tr>\n <tr>\n <td rowspan=\"3\" style=\"width:144px;height:7px;\">\n \n Lab technologist (3)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Charles Mutinda\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Diploma in medical Laboratory sciences\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Sample processing, Biorepository and CBC testing\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Josephart Sibo\n </td>\n <td style=\"width:131px;height:7px;\">\n \n Diploma in medical Laboratory sciences\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Sample processing, Biorepository and CBC testing\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Maurice Okello\n </td>\n <td style=\"width:131px;height:7px;\">\n \n BSC. in medical Laboratory\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Sample processing, Biorepository and CBC testing\n </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:144px;height:7px;\">\n \n Data Manager (2)\n </td>\n <td style=\"width:139px;height:7px;\">\n \n Agnes Ndirangu\n </td>\n <td style=\"width:131px;height:7px;\">\n \n BSC. Statistics\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data cleaning, query management\n </td>\n </tr>\n <tr>\n <td style=\"width:139px;height:7px;\">\n \n Charles Muiruri\n </td>\n <td style=\"width:131px;height:7px;\">\n \n BSC. Applied Statistics with Computing\n </td>\n <td style=\"width:240px;height:7px;\">\n \n Data cleaning, query management\n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:654px;height:7px;\">\n \n Site Facilities\n <ul>\n <li>\n Office space with adequate resources i.e. furniture, internet connectivity and computers</li>\n <li>\n Access to programme transport facilitation for community follow up</li>\n <li>\n Laboratory network –Migori county referral hospital, St.Joseph mission and Lancet Laboratories</li>\n <li>\n Migori County Hospital: Paediatric ward, maternal and child health clinic, paediatric outpatient clinic</li>\n <li>\n </li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:654px;height:7px;\">\n \n Emergency facilities\n <ul>\n <li>\n No Intensive care unit within Migori County</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:654px;height:7px;\">\n \n Other Infrastructure\n <ul>\n <li>\n Work in liaison with hospital paediatric consultants and other county health staff.</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n\n \n
 other_details_explanation\n The trial will be done in the host country of the sponsor i.e University of Oxford (UK) and Kenya Medical Research Institute collaborative progarmme (KEMRI-Wellcome Trust Research Programme) who have taken the sponsor role for Kenya sites, and all other Country Sites.\n\n Kenya and other sites in Africa and South East Asia have a high burden of the condition under investigation i.e severe malnutrition affecting the intended population of children below 5 years of age. Gains from this trial would have significant impact in improving health outcomes in the study countries.\n
 other_details_regulatory_notapproved<ol>\n <li>\n National Drug Authority, Uganda- date of application 01/02/2021</li>\n</ol>\n
 other_details_regulatory_approved\n Directorate General of Drug Administration(DGDA), Bangaldesh; date of approval: 15/03/2021; number of sites:1\n\n Poisons and Medicines Regulatory Authority (PMRA), Malawi; date of conditional approval:12/04/2021; number of sites:1\n\n \n\n \n
 other_details_regulatory_rejected\n None\n
 other_details_regulatory_halted\n Not applicable\n
 estimated_durationThe trial will require approximately 3 to 4 years of enrolment and 5 years to complete from the start to the end of analysis.
 design_controlled_randomisedYes
 design_controlled_openNo
 design_controlled_single_blindNo
 design_controlled_double_blindYes
 design_controlled_parallel_groupYes
 design_controlled_cross_overNo
 design_controlled_otherYes
 design_controlled_specifyFactorial, Adaptive
 design_controlled_comparatorYes
 design_controlled_other_medicinalNo
 design_controlled_placeboYes
 design_controlled_medicinal_otherNo
 design_controlled_medicinal_specify
 single_site_member_stateNo
 location_of_area
 single_site_physical_address
 single_site_contact_person
 single_site_telephone
 multiple_sites_member_stateYes
 multiple_countriesYes
 multiple_member_states4
 number_of_sites4
 multi_country_listKenya, Uganda, Malawi and Bangladesh.
 data_monitoring_committeeYes
 total_enrolment_per_siteRecruitment will be competitive across all participating sites in all stages of the trial. Minimum 0, maximum 500 for each site\n
 total_participants_worldwide1200
 population_less_than_18_yearsYes
 population_uteroNo
 population_preterm_newbornNo
 population_newbornNo
 population_infant_and_toddlerYes
 population_childrenYes
 population_adolescentNo
 population_above_18No
 population_adultNo
 population_elderlyNo
 gender_female1
 gender_male1
 subjects_healthyNo
 subjects_patientsYes
 subjects_vulnerable_populationsYes
 subjects_women_child_bearingNo
 subjects_women_using_contraceptionNo
 subjects_pregnant_womenNo
 subjects_nursing_womenNo
 subjects_emergency_situationNo
 subjects_incapable_consentYes
 subjects_specifyWe will enroll children between the ages of 2 months and 59 months(inclusive). Informed consent will be sought from the child\'s care provider.
 subjects_othersNo
 subjects_others_specify
 investigator1_given_nameIsaiah
 investigator1_middle_name
 investigator1_family_nameNjagi
 investigator1_qualificationMicrobiology & public health
 investigator1_professional_addressP.O Box 43640 â€“ 00100, 197 Lenana Place, Off Lenana Road. Nairobi
 investigator1_telephone+254709983029
 investigator1_emailINjagi@kemri-wellcome.org
 organisations_transferred_Yes
 number_participantsParticipating sites are: 1) Kilifi County Hospital, Kenya; 2) Coast General Hospital, Mombasa, Kenya; 3) Mbagathi Sub-County Hospital, Nairobi, Kenya; 4) Migori County Hospital and Ombo Mission Hospital, Migori, Kenya; 5) Queen Elizabeth Central Hospital (QECH) Blantyre, Malawi; 6) the International Centre for Diarrhoeal Disease Research Hospital, Dhaka, Bangladesh (ICCDR-B); and 7) Mulago National Referral Hospital, Kampala, Uganda. Sites #1, #5, #6, and #7 will participate in Stage I to enrol the first 200 participants. In stages II (additional n=200 i.e total =400) and III (anticipated total n=1200) recruitment may include sites #2, #3 and #4 in Kenya. \n\nRecruitment will be competitive across all participating sites in all stages of the trial. \nExpected numbers in Kenya will be a minimum of 20 and a maximum of 1000\n
 notification
 approval_date08-06-2021
 submitted1
 deleted0
 deleted_date(null)
 deactivated0
 date_submitted24-05-2021
 is_child0
 unsubmitted0
 initial_date_submitted(null)
 admin_stopped0
 admin_stopped_reason(null)
 approved2
 approved_reasonApplication approved by the experts
 final_report(null)
 implication_results(null)
 quantity_imported(null)
 quantity_dispensed(null)
 quantity_destroyed(null)
 quantity_exported(null)
 balance_site(null)
 final_date(null)
 modified2023-11-10 13:02:24
 created2021-01-12 14:55:39
 total_sites(null)
 ecitizen_invoice(null)
 InvestigatorContact(array)
 0(array)
 id613
 application_id967
 given_nameRobert
 middle_name
 family_nameBandsma
 qualificationPhD in Nutrition & Metabolism
 professional_addressThe Hospital for Sick Children, 555 University Avenue Toronto, Ontario, Canada M5G 1X8
 telephone+14168135492
 emailrobert.bandsma@sickkids.ca
 created2021-01-12 15:04:36
 modified2021-05-24 12:13:16
 SiteDetail(array)
 0(array)
 id846
 application_id967
 county_id3
 site_nameKilifi County Hospital
 physical_addressBofa Road
 contact_detailsP.O. BOX 9- 80108, Kilifi.
 contact_personShalton Mwaringa
 site_capacity(null)
 misc(null)
 created2021-01-12 15:04:36
 modified2021-05-24 12:13:16
 County(array)
 id3
 county_nameKilifi
 created2012-05-31 16:15:49
 modified2012-05-31 16:15:49
 1(array)
 id847
 application_id967
 county_id1
 site_nameCoast General Hospital
 physical_addressKisauni Road
 contact_detailsP.O. Box: 90231-80100 Mombasa.
 contact_personLaura Mwalekwa
 site_capacity(null)
 misc(null)
 created2021-01-20 10:06:10
 modified2021-05-24 12:13:16
 County(array)
 id1
 county_nameMombasa
 created2012-05-31 16:15:11
 modified2012-07-09 13:06:23
 2(array)
 id848
 application_id967
 county_id47
 site_nameMbagathi Hospital
 physical_addressKenyatta Market
 contact_detailsP.O.Box: 20725-00202 , Nairobi, Kenya
 contact_personMolline Timbwa
 site_capacity(null)
 misc(null)
 created2021-01-20 10:06:10
 modified2021-05-24 12:13:16
 County(array)
 id47
 county_nameNairobi City
 created2012-06-15 10:27:40
 modified2012-06-15 10:27:40
 3(array)
 id849
 application_id967
 county_id44
 site_nameMigori County Hospital
 physical_addressSuna-Migori
 contact_detailsP.O BOX 202-40400, Suna-Migori
 contact_personDr. Benson Singa
 site_capacity(null)
 misc(null)
 created2021-01-20 10:06:10
 modified2021-05-24 12:13:16
 County(array)
 id44
 county_nameMigori
 created2012-06-15 10:27:16
 modified2012-06-15 10:27:16
 Sponsor(array)
 0(array)
 id476
 application_id967
 sponsorUniversity of Oxford
 sponsor_typeOthers
 contact_person
 addressWellington Square, Oxford, OX1 2JD United Kingdom.
 telephone_number+44 1865 270000
 fax_number
 cell_number+44 1865 270000
 email_addressoxtrec@admin.ox.ac.uk
 created2021-01-12 15:04:36
 modified2021-05-24 12:13:16
 2(array)
 Application(array)
 id221
 user_id98
 trial_status_id5
 abstract_of_study<div data-canvas-width=\"70.23521854019165\" data-font-name=\"g_font_75_0\" dir=\"ltr\" style=\"font-size: 12px; font-family: sans-serif; left: 82.6667px; top: 396.559px; transform: scale(1.06417, 1); transform-origin: 0% 0% 0px;\">\n Background</div>\n<div data-canvas-width=\"447.92438385963464\" data-font-name=\"g_font_72_0\" dir=\"ltr\" style=\"font-size: 13.3333px; font-family: serif; left: 82.6667px; top: 427.892px; transform: scale(1.01295, 1); transform-origin: 0% 0% 0px;\">\n Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations.</div>\n<div data-canvas-width=\"5.567938049316407\" data-font-name=\"g_font_146_0\" dir=\"ltr\" style=\"font-size: 12px; font-family: monospace; left: 127.738px; top: 448.559px; transform: scale(0.79542, 1); transform-origin: 0% 0% 0px;\">\n </div>\n<div data-canvas-width=\"5.567938049316407\" data-font-name=\"g_font_146_0\" dir=\"ltr\" style=\"font-size: 12px; font-family: monospace; left: 127.738px; top: 448.559px; transform: scale(0.79542, 1); transform-origin: 0% 0% 0px;\">\n Methods</div>\n<div data-canvas-width=\"221.51557414627075\" data-font-name=\"g_font_72_0\" dir=\"ltr\" style=\"font-size: 13.3333px; font-family: serif; left: 82.6667px; top: 575.892px; transform: scale(1.00819, 1); transform-origin: 0% 0% 0px;\">\n We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1–serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1–seronegative partner in each couple was randomly assigned to one of three study regimens — once-daily tenofovir (TDF), combination tenofovir– emtricitabine (TDF–FTC), or matching placebo — and followed monthly for up to 36 months. At enrollment, the HIV-1–seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services.</div>\n<div data-canvas-width=\"42.34752882766724\" data-font-name=\"g_font_75_0\" dir=\"ltr\" style=\"font-size: 12px; font-family: sans-serif; left: 82.6667px; top: 596.559px; transform: scale(0.984826, 1); transform-origin: 0% 0% 0px;\">\n </div>\n<div data-canvas-width=\"42.34752882766724\" data-font-name=\"g_font_75_0\" dir=\"ltr\" style=\"font-size: 12px; font-family: sans-serif; left: 82.6667px; top: 596.559px; transform: scale(0.984826, 1); transform-origin: 0% 0% 0px;\">\n Results</div>\n<div data-canvas-width=\"185.74295554542536\" data-font-name=\"g_font_72_0\" dir=\"ltr\" style=\"font-size: 13.3333px; font-family: serif; left: 348.955px; top: 771.892px; transform: scale(1.00947, 1); transform-origin: 0% 0% 0px;\">\n We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned toTDF, 1579 to TDF–FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1–seronegative partner was male. Among HIV-1–seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF–FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF–FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF–FTC and TDF alone against HIV-1 were not significantly different (P =0.23), and both study medications</div>\n<div data-canvas-width=\"447.93771692657475\" data-font-name=\"g_font_72_0\" dir=\"ltr\" style=\"font-size: 13.3333px; font-family: serif; left: 82.68px; top: 835.892px; transform: scale(1.01982, 1); transform-origin: 0% 0% 0px;\">\n significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline,and among these eight, antiretroviral resistance developed in two during the study.</div>\n<div data-canvas-width=\"73.4751824913025\" data-font-name=\"g_font_75_0\" dir=\"ltr\" style=\"font-size: 12px; font-family: sans-serif; left: 82.6667px; top: 856.559px; transform: scale(1.04965, 1); transform-origin: 0% 0% 0px;\">\n </div>\n<div data-canvas-width=\"73.4751824913025\" data-font-name=\"g_font_75_0\" dir=\"ltr\" style=\"font-size: 12px; font-family: sans-serif; left: 82.6667px; top: 856.559px; transform: scale(1.04965, 1); transform-origin: 0% 0% 0px;\">\n Conclusions</div>\n<div data-canvas-width=\"451.95097007560736\" data-font-name=\"g_font_72_0\" dir=\"ltr\" style=\"font-size: 13.3333px; font-family: serif; left: 82.6667px; top: 887.892px; transform: scale(0.978072, 1); transform-origin: 0% 0% 0px;\">\n Oral TDF and TDF–FTC both protect against HIV-1 infection in heterosexual menand women.</div>\n
 study_title\n Parallel comparison of Tenofovir and Emtricitabine/Tenofovir pre exposure prophylaxis to prevent HIV-1 acquisition within HIV-1 discordant couples\n
 laymans_summary(null)
 short_titlePartners PrEP Study
 protocol_noECCT/08/20/01
 version_no3
 date_of_protocol12-10-2007
 study_drugTenofovir and Emtricitabine/Tenofovir
 disease_conditionpre exposure prophylaxis against HIV
 product_type_biologicals0
 product_type_proteins0
 product_type_immunologicals0
 product_type_vaccines0
 product_type_hormones0
 product_type_toxoid0
 product_type_chemical1
 product_type_medical_device0
 product_type_chemical_nameTenofovir and Emtricitabine/Tenofovir
 product_type_medical_device_name
 comparator(null)
 comparator_name(null)
 comparator_registered(null)
 comparator_countries(null)
 ecct_not_applicable0
 ecct_ref_number
 email_addressakaggiah@gmail.com
 applicant_covering_letter1
 applicant_protocol1
 applicant_patient_information1
 applicant_investigators_brochure1
 applicant_investigators_cv1
 applicant_signed_declaration1
 applicant_financial_declaration1
 applicant_gmp_certificate1
 applicant_indemnity_cover1
 applicant_opinion_letter1
 applicant_approval_letter0
 applicant_statement1
 applicant_participating_countries0
 applicant_addendum0
 applicant_fees1
 applicant_complete_form(null)
 applicant_impd(null)
 applicant_prev_data(null)
 applicant_stability_data(null)
 applicant_analysis_cert(null)
 applicant_pictorial_sample(null)
 applicant_gcp_training(null)
 applicant_dsmb_charter(null)
 applicant_detailed_budget(null)
 applicant_indemnity_pi(null)
 applicant_practice_license(null)
 applicant_registration_ctr(null)
 applicant_pan_african(null)
 applicant_hard_copies(null)
 applicant_signed_checklist(null)
 statistical_analysis_plan(null)
 applicant_contractual_agreement(null)
 declaration_applicantProf. James Kiarie/Dr. Anne Kaggiah
 declaration_date110-10-2013
 declaration_principal_investigatorJared Baeten
 declaration_date210-10-2013
 placebo_presentYes
 study_objectives(null)
 principal_inclusion_criteria\n Inclusion Criteria for HIV-1 uninfected partner:\n<ul style=\"margin-top:1ex; margin-bottom:1ex;\">\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Partner within an HIV-1 discordant heterosexual relationship</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n One partner meets study eligibility for HIV-1 uninfected study participant and the other partner meets study eligibility criteria for HIV-1 infected participant</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Plan to remain in the relationship for the duration of the study period</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Adequate renal, hepatic & hematologic function</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Negative Hepatitis B surface antigen test</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Willing and able to provide written informed consent & locator information</li>\n</ul>\n\n \n\n Inclusion Criteria for HIV-1 infected partner:\n<ul style=\"margin-top:1ex; margin-bottom:1ex;\">\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Partner within an HIV-1 discordant heterosexual relationship</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n One partner meets study eligibility for HIV-1 uninfected study participant and the other partner meets study eligibility criteria for HIV-1 infected participant</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n HIV-1 infected based on positive EIA</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n No history of any clinical AIDS-defining diagnoses</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Plan to remain in the relationship for the duration of the study period</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Willing and able to provide written informed consent & locator information</li>\n</ul>\n
 principal_exclusion_criteria\n Exclusion Criteria for HIV-1 uninfected partner:\n<ul style=\"margin-top:1ex; margin-bottom:1ex;\">\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Current pregnancy, or planning to become pregnant during the study period</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Currently breastfeeding</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Concurrent enrollment in another HIV-1 vaccine or prevention trial</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Receiving ongoing antiretroviral therapy</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Repeated positive urine dipstick tests for glycosuria or proteinuria</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Active and serious infections</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n History of pathological bone fractures not related to trauma</li>\n</ul>\n\n \n\n Exclusion Criteria for HIV-1 infected partner:\n<ul style=\"margin-top:1ex; margin-bottom:1ex;\">\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Current use of antiretroviral therapy</li>\n <li class=\"color-bullet\" style=\"margin-top:0.7ex;\">\n Concurrent enrollment in another HIV-1 treatment trial</li>\n</ul>\n\n \n
 primary_end_points\n 1. HIV infection among HIV uninfected partner (seroconversion)\n
 scope_diagnosis0
 scope_prophylaxis1
 scope_therapy0
 scope_safety1
 scope_efficacy1
 scope_pharmacokinetic0
 scope_pharmacodynamic0
 scope_bioequivalence0
 scope_dose_response0
 scope_pharmacogenetic0
 scope_pharmacogenomic0
 scope_pharmacoecomomic0
 scope_others0
 scope_others_specify
 trial_human_pharmacology0
 trial_administration_humans0
 trial_bioequivalence_study0
 trial_other0
 trial_other_specify
 trial_therapeutic_exploratory0
 trial_therapeutic_confirmatory1
 trial_therapeutic_use0
 design_controlledYes
 site_capacity(null)
 staff_numbers\n Prof. James Kiarie - Principle Investigator- MBCHB, MMED,MPH\n\n Anne Kaggiah - Study coordinator - MD\n\n Milcah Ariongo- Study administrator - Bsc. Nursing\n\n William Obara - lab manager\n\n Jerusha Malubi - Data manager - Community Nursing\n\n Shiphrah Maina - Retention manager - Social sciencea\n\n Grace Wambugu - Pharmcay technologist\n\n Joseph - Driver\n\n Site facilites - reception, pharmacy, labaroratory, 6 clinic rooms, 2 counseling rooms, data room, one vehicle\n
 other_details_explanation\n Majority of new HIV infections are in Africa occur among HIV discordant couples. This was validated in 2005 in a Ugandan population based serosurvey which showed upto 65% of incident infections occur among married couples.\n\n Only a trial among HIV discordant couples can examine the impact of biological and behavioural characteristics of both HIV susceptible and infected partners on the efficacy of pre exposure prophylaxis.\n
 other_details_regulatory_notapproved\n Not applicable\n
 other_details_regulatory_approved\n Kenyatta National Hospital/University of Nairobi Ethics and Research Committee - Dates of approval- 9th October 2008, 9th October 2009, 9 October 2010, 9th October 2011, 9th October 2012, 9th October 2013\n\n University of Washington Review Board - Dates of approval - 8th December 2008, 8th Dec 2009, 8th Dec 2010, 8th Dec 2011, 8th Dec 2012\n\n University of Wahington Human Subject Division- Dates of approval - 28th Sep 2008, 28th Sep 2009, 28th Sep 2010, 28th Sep 2011, 28th Sep 2012, 28th Sep 2013\n\n Pharmacy Board of Kenya - Dates of approval- 11th Oct 2008, 11th Oct 2009, 11th Oct 2010, 11th Oct 2011, 11th Oct 2012\n
 other_details_regulatory_rejected\n Not applicable\n
 other_details_regulatory_halted\n Not applicable\n
 estimated_duration4 years
 design_controlled_randomisedYes
 design_controlled_openNo
 design_controlled_single_blindNo
 design_controlled_double_blindYes
 design_controlled_parallel_groupYes
 design_controlled_cross_overNo
 design_controlled_otherNo
 design_controlled_specify
 design_controlled_comparatorActive Comparator: I Drug
 design_controlled_other_medicinalNo
 design_controlled_placeboYes
 design_controlled_medicinal_otherNo
 design_controlled_medicinal_specify
 single_site_member_stateNo
 location_of_area
 single_site_physical_address
 single_site_contact_person
 single_site_telephone
 multiple_sites_member_stateYes
 multiple_countriesYes
 multiple_member_states2
 number_of_sites4
 multi_country_listUganda \nKenya
 data_monitoring_committeeYes
 total_enrolment_per_siteEldoret-488 HIV-1 discordant couples, Kisumu -629 HIV-1 discordant couples, Nairobi- 485 HIV-1 discordant couples, Thika - 496 HIV-1 discordant couples
 total_participants_worldwide4758 HIV-1 discordant couples
 population_less_than_18_yearsNo
 population_uteroNo
 population_preterm_newbornNo
 population_newbornNo
 population_infant_and_toddlerNo
 population_childrenNo
 population_adolescentNo
 population_above_18Yes
 population_adultYes
 population_elderlyNo
 gender_female1
 gender_male1
 subjects_healthyYes
 subjects_patientsNo
 subjects_vulnerable_populationsNo
 subjects_women_child_bearingNo
 subjects_women_using_contraceptionNo
 subjects_pregnant_womenNo
 subjects_nursing_womenNo
 subjects_emergency_situationNo
 subjects_incapable_consentNo
 subjects_specify
 subjects_othersNo
 subjects_others_specify
 investigator1_given_nameAndrew
 investigator1_middle_name
 investigator1_family_nameMujugira
 investigator1_qualification MBChB MSc MPH
 investigator1_professional_addressKampala
 investigator1_telephone+256 754 173 225
 investigator1_emailmujugira@uw.edu
 organisations_transferred_No
 number_participants2098 HIV-1 discordant couples
 notification
 approval_date09-10-2013
 submitted1
 deleted0
 deleted_date(null)
 deactivated0
 date_submitted19-10-2013
 is_child0
 unsubmitted0
 initial_date_submitted(null)
 admin_stopped0
 admin_stopped_reason(null)
 approved2
 approved_reason
 final_report\n Sponsor:Bill and Melinda Gates Foundation\n<h4 class=\"text-success\" style=\"margin: 10px 0px; font-family: "Helvetica Neue", Helvetica, Arial, sans-serif; line-height: 20px; color: rgb(70, 136, 71); text-rendering: optimizelegibility; font-size: 17.5px;\">\n ECCT/08/20/01</h4>\n\n Summary\n\n Objective:\n\n This research studied two medications that suppress the HIV virus. One medication called Tenofovir and second medication was a combination of Tenofovir and Emtricitabine. The combination was known as Truvada®. Tenofovir and Truvada® are pills used to treat people already infected with HIV. Studies showed that these medications were safe when used once per day as treatment of HIV by HIV-infected people. Tenofovir and Truvada® are not cures for HIV, but they are very effective in suppressing HIV in people who are infected and in improving their health and immune function.\n\n \n\n The purpose the study was to find out if taking Tenofovir or Truvada® every day coulf prevent HIV-uninfected men and women from getting the HIV virus from their infected partner. This is called pre-exposure prophylaxis. The study also determined whether Tenofovir and Truvada were safe and do not produce health problems when taken by HIV-uninfected men and women.\n\n \n\n Population:\n\n 4758 couples, all from Africa, were enrolled in the parent study. All the couples were HIV-discordant, meaning that one person had HIV and the other person did not have HIV. The enrolment goal at the Nairobi site was to enroll 500-800 couples as subjects. 485 couples were enrolled at the Nairobi site at the close of enrolment. The HIV infected subjects must have had a CD4 count ≥250 cells/mm3 and must not have otherwise qualified for initiation of ART at the time of study screening and enrollment. The HIV-1 uninfected partner in the couple must have reported an average of 6 times vaginal intercourse with the partner in the 3 months prior to screening and enrolment. Eligibility determination of the HIV-1 uninfected partner included normal renal, liver, and haematologic function based on clinical and laboratory screening. The HIV-1 uninfected partner must have been uninfected with hepatitis B. Hepatitis B seronegative participants were offered hepatitis B vaccination at no cost.\n\n \n\n Procedures\n\n Each eligible participant underwent a physical examination. For women, samples from the genital area were collected to test for sexually transmitted infections. A pap smear was also performed. A urine sample was used for a pregnancy test. For men, a urine test was used to test for sexually transmitted infections. Both men and women were asked permission to obtain a blood sample of up to 29.5ml-about 2 tablespoons. The blood sample were used for HIV, syphilis, hepatitis B and Herpes Simplex virus test.\n\n After the enrolment visit, each participant was scheduled for a follow-up visit. The HIV-uninfected participants were followed up monthly. HIV-1 rapid testing was performed, in the context of pre-test, risk reduction and post test counseling. Counseling included reminders to contact study staff with questions, as well as counseling not to share the study medication.\n\n For women, a pregnancy test was performed at these monthly visits and counseling about contraceptives. In the event of a positive pregnancy test, the study medication was stopped.\n\n Follow-up visit for HIV-infected participants occured quarterly. During these visits, a physical exam was performed and the participants were asked questions about their sexual practices and educated on ways to avoid HIV and other sexually transmitted infections. If needed, participants received medical care or referrals and other services.\n\n All participants received couple counseling at screening, enrollment, and during follow-up that include counseling about risks for transmission and strategies to reduce the risk of transmission. Participants underwent genital exams, HIV-1 and STI counseling and testing, STI treatment, and HBV vaccination if indicated. They were offered participation in support groups for HIV-1 infected and HIV-1 uninfected persons and also provided with condoms and STI treatment free of charge.\n\n Each couple was in the study for a minimum of 24 months and up to a maximum of 36 months. Those who become HIV infected during the study were asked to continue follow-up for one year after infection, regardless of when during the 36 months of maximum follow-up the HIV infection occured. \n\n Starting 1 June 2012, close out of the study began. Active arm participants started having a STOP visit at their next quarterly visit that is at least month 24 (consistent with the informed consent). Approximately half of active arm participants had already completed 36 months of follow-up; thus, the remainder exited at/after month 24. Under this schedule, most of the remaining half will exited in June, July, and August, with a small number in September. Placebo conversion enrolees were followed through 12 study months – ending between September and December 2012, depending on when they were re-randomized. Therefore, all participants (including placebo conversion participants) completed follow up before 30 December 2012,i.e, all study visits. The study drugs and placebos were destroyed as per the Pharmacy and Poisons Board regulations and supervision in 2012.\n\n Since then the study team has been appying for annual renewal for data analysis from the respective IRB authorities. Attached with these summary is the progress report for various publications.\n
 implication_results(null)
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 modified2019-09-10 12:18:19
 created2013-10-09 12:20:14
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 id151
 application_id221
 given_nameJames
 middle_nameNjogu
 family_nameKiarie
 qualificationMBCHB, MMED, MPH
 professional_addressP.O Box 202723-00202
 telephone0733771288
 emailjkiarie@swiftkenya.com
 created2013-10-09 12:47:49
 modified2013-10-19 13:24:08
 1(array)
 id152
 application_id221
 given_nameCAREY
 middle_name
 family_nameFARQUHAR,
 qualificationMD, MPH
 professional_address325 9th Avenue, Box 359909, Seattle, WA 98104
 telephone(206) 543-4278
 emailcfarq@u.washington.edu
 created2013-10-10 17:52:09
 modified2013-10-19 13:24:08
 2(array)
 id153
 application_id221
 given_nameGrace
 middle_nameJohn
 family_nameStewart
 qualificationB.S. M.D., M.P.H., Ph.D.,
 professional_address325 Ninth Ave, Box 359909Seattle, Washington 98104-2499
 telephone 206-543-4278
 emailgjohn@u.washington.edu
 created2013-10-10 17:53:55
 modified2013-10-19 13:24:08
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 0(array)
 id190
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 county_id47
 site_nameNairobi
 physical_addressKNH opposite KNH Police station
 contact_detailsP.O Box 20723-00202
 contact_personAnne Kaggiah
 site_capacity(null)
 misc(null)
 created2013-10-09 12:47:49
 modified2013-10-19 13:24:08
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 id47
 county_nameNairobi City
 created2012-06-15 10:27:40
 modified2012-06-15 10:27:40
 1(array)
 id191
 application_id221
 county_id22
 site_nameThika
 physical_addressThika town opposite Tuskys
 contact_details254 6722561
 contact_personKenneth Ngure
 site_capacity(null)
 misc(null)
 created2013-10-09 17:20:46
 modified2013-10-19 13:24:08
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 id22
 county_nameKiambu
 created2012-06-15 10:24:37
 modified2012-06-15 10:24:37
 2(array)
 id192
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 county_id27
 site_nameEldoret
 physical_addressEldoret Town
 contact_details254 53 5361101
 contact_personDismas oketch
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 created2013-10-09 17:20:46
 modified2013-10-19 13:24:08
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 id27
 county_nameUasin Gishu
 created2012-06-15 10:25:15
 modified2012-06-15 10:25:15
 3(array)
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 county_id42
 site_nameKisumu
 physical_addressKisumu Town
 contact_details254 572 021 036
 contact_personJosephine Odoyo
 site_capacity(null)
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 created2013-10-09 17:20:46
 modified2013-10-19 13:24:08
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 id42
 county_nameKisumu
 created2012-06-15 10:27:02
 modified2012-06-15 10:27:02
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 0(array)
 id119
 application_id221
 sponsorUniversity of Wahington
 sponsor_type(null)
 contact_personConnie Celum
 addressP.O Box 359927 Cabrini Medical Tower, Suite 1300 901 Boren Avenue Seattle Washington 98104
 telephone_number206 5203825
 fax_number
 cell_number206 520381
 email_addressccelum@u.wahington.edu
 created2013-10-09 12:47:49
 modified2013-10-19 13:24:08
 3(array)
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 abstract_of_study\n HIV-1 uninfected individuals within HIV-1 discordant partnerships are at high-risk for HIV acquisition. The majority of HIV-1 transmissions to adults in Africa occur within stable, HIV-1 discordant couples. Novel strategies to prevent HIV-1 transmission within discordant couples, especially interventions that might allow pregnancy to occur safely, are urgently needed. Pre-exposure chemoprophylaxis, in which an HIV-1 uninfected individual at high risk for contracting HIV-1 takes antiretroviral medications to maintain blood and genital drug levels sufficient to prevent HIV-1 acquisition, has been proposed as a potential HIV-1 prevention strategy. A randomized , blinded, placebo controlled trial is required to demonstrate if PrEP decreases HIV-1 acquisition and has an acceptable safety profile when given to HIV-1 uninfected individuals within HIV-1 discordant partnerships.\n\n Both Tenofovir disoproxil fumarate (TDF) and co-formulated Emtricitabine/Tenofovir disoproxil fumarate (FTC/TDF) have been proposed as possible safe and effective medications to serve as pre-exposure chemoprophylaxis. The potential for differential safety, cost, and efficacy for these two medications justifies evaluating both, against placebo, in single clinical trial. This trial will directly answer whether PrEP decreases HIV-1 acquisition among HIV-1 uninfected individuals within HIV-1 discordant couples, a very high-risk heterosexual population who could benefit from this type of intervention, if found to be safe and efficacious.\n\n Primary Objectives:\n<ol>\n <li>\n To determine if once-daily, oral PrEP with TDF or FTC/TDF provides additional protective benefit in preventing HIV-1 acquisition among HIV-1 uninfected persons within heterosexual HIV-1 discordant couples who are also receiving standard prevention interventions.</li>\n <li>\n To assess the safety of daily PrEP using TDF or TDF/FTC by comparing rates of adverse events (AEs) among HIV-1 uninfected individuals randomized to TDF or FTC/TDF PrEP to those randomized to placebo.</li>\n</ol>\n\n Secondary Objectives: \n<ol>\n <li>\n Factors influencing efficacy</li>\n</ol>\n<ul>\n <li>\n To evaluate the efficacy of PrEP by the level of HIV-1 exposure for HIV-1 uninfected partners within HIV-1 discordant couples, defined by the frequency of sexual activity and the HIV-1 viral load in the HIV-1 infected partner.</li>\n <li>\n To assess efficacy of PrEP by gender of the HIV-1 uninfected partner.</li>\n <li>\n To measure the effect on efficacy of other factors, including CD4 count of the HIV-1 infected partner and, for both partners, herpes simplex virus type 2 (HSV-2) serostatus, sexually transmitted infections (STIs), and male circumcision.</li>\n</ul>\n\n 2. Adherence:\n<ul>\n <li>\n To assess adherence to once daily TDF or FTC/TDF PrEP among HIV-1 uninfected persons within HIV-1 discordant couples, and the effect of adherence on efficacy of PrEP to prevent HIV-1 acquisition.</li>\n <li>\n To evaluate the frequency of PrEP drug sharing between the HIV-1 uninfected and HIV-1 infected partners within HIV-1 discordant couples, as measured by drug assays in HIV-1 infected and uninfected partners.</li>\n</ul>\n\n 3. Risk Compensation:\n<ul>\n <li>\n To characterize the association of once daily TDF or FTC/TDF PrEP with sexual bahaviour change of HIV-1 uninfected individuals within HIV-1 discordant partnerships.</li>\n <li>\n To compare risk bahaviors among HIV-1 discordant couples previously enrolled in the Partners in Prevention trial(which evaluated the efficacy of HSV-2 suppressive therapy when given to the HIV-1 infected partner for preventing HIV-1 transmission), by examining changes in sexual behaviors when the HIV-1 infected versus HIV-1 uninfected partner is receiving a study drug.</li>\n</ul>\n\n 4. Safety\n<ul>\n <li>\n To assess the effect of TDF and FTC/TDF chemoprophylaxis on the rate of congenital abnormalities and growth among infants born to HIV-1 uninfected female participants who become pregnant during the study (and in whom study drug is stopped at the time pregnancy is detected, using monthly pregnancy testing).</li>\n</ul>\n\n 5. Effect of PrEP on early HIV-1 disease\n\n Among those initially HIV-1 uninfected individuals in the trial who seroconvert to HIV-1, to assess the effect of PrEP on:\n<ul>\n <li style=\"margin-left: 49.2pt;\">\n Plasma HIV-1 viral load and CD4 cell counts during at least 12 months after HIV-1 seroconversion.</li>\n <li style=\"margin-left: 49.2pt;\">\n Frequency of genotypic and phenotypic antiretroviral drug resistance .</li>\n <li style=\"margin-left: 49.2pt;\">\n Other clinical, immunologic, and virologic parameters of HIV-1 disease.</li>\n</ul>\n\n Tertiary Objectives:\n\n To utilize stored samples for evaluation of immunogenetic and virologic determinants of HIV-1 transmission between transmitting and non-transmitting HIV-1 discordant couples, including viral phenotype and genotype, HIV-1 co- receptor usage, innate immune function polymorphisms, human leukocyte\n
 study_title\n Parallel Comparison of Tenofovir and Emtricitabine/Tenofovir Pre-exposure Prophylaxis to Prevent HIV-1 Acquisition within HIV-1 Discordant Couples. \n
 laymans_summary(null)
 short_titlePartners PrEP Study
 protocol_noECCT/08/08/03
 version_no3.0
 date_of_protocol12-10-2007
 study_drugTenofovir Disoproxyl Fumarate, Emtricitabine/Tenofovir Disoproxyl Fumarate or Placebo
 disease_conditionHIV Infection
 product_type_biologicals0
 product_type_proteins0
 product_type_immunologicals0
 product_type_vaccines0
 product_type_hormones0
 product_type_toxoid0
 product_type_chemical1
 product_type_medical_device0
 product_type_chemical_nameTenofovir Disoproxyl Fumarate, Emtricitabine/Tenofovir Disoproxyl Fumarate or Placebo
 product_type_medical_device_name
 comparator(null)
 comparator_name(null)
 comparator_registered(null)
 comparator_countries(null)
 ecct_not_applicable0
 ecct_ref_number
 email_addressRwamba@csrtkenya.org
 applicant_covering_letter1
 applicant_protocol1
 applicant_patient_information1
 applicant_investigators_brochure1
 applicant_investigators_cv1
 applicant_signed_declaration1
 applicant_financial_declaration1
 applicant_gmp_certificate1
 applicant_indemnity_cover1
 applicant_opinion_letter1
 applicant_approval_letter0
 applicant_statement1
 applicant_participating_countries0
 applicant_addendum0
 applicant_fees1
 applicant_complete_form(null)
 applicant_impd(null)
 applicant_prev_data(null)
 applicant_stability_data(null)
 applicant_analysis_cert(null)
 applicant_pictorial_sample(null)
 applicant_gcp_training(null)
 applicant_dsmb_charter(null)
 applicant_detailed_budget(null)
 applicant_indemnity_pi(null)
 applicant_practice_license(null)
 applicant_registration_ctr(null)
 applicant_pan_african(null)
 applicant_hard_copies(null)
 applicant_signed_checklist(null)
 statistical_analysis_plan(null)
 applicant_contractual_agreement(null)
 declaration_applicantDr. Kenneth Ngure
 declaration_date108-08-2013
 declaration_principal_investigatorDr. Nelly R. Mugo
 declaration_date208-08-2013
 placebo_presentYes
 study_objectives(null)
 principal_inclusion_criteria<div>\n Potential partner (HIV-1 uninfected) participants must meet the following criteria (by self-report, unless otherwise indicated) in order to be eligible for inclusion in the study:</div>\n<ul>\n <li>\n Of legal age to provide independent informed consent for research per local regulations and guidelines</li>\n <li>\n Age ≥18 and ≤65</li>\n</ul>\n\n This specific additional age restriction reflects that pharmacokinetic data for TDF and FTC/TDF are unavailable or are limited for individuals less than 18 years of age or greater than 65 years of age.\n<ul>\n <li>\n Able and willing to provide written informed consent to be screened for and to take part in the study</li>\n <li>\n Part of a heterosexual couple in which one partner meets the study eligibility criteria for index (HIV-1 infected) participants and the other partner meets the study eligibility criteria for partner (HIV-1 uninfected) participants, including the following criteria for the couple:</li>\n</ul>\n<ol>\n <li>\n Are partners who are sexually active (defined as having had vaginal intercourse with the partner [HIV-1 uninfected] participant at least 6 times in the last three months)</li>\n <li>\n plan to remain in the relationship for the duration of the study period. Each study site will develop appropriate criteria for determining whether a couple is likely to remain in the relationship (i.e., married, duration of partnership, cohabitation, children in the home).</li>\n</ol>\n<div>\n <ol>\n <li>\n HIV-1 uninfected based on parallel negative HIV-1 rapid tests, both at study screening and at the enrollment visit</li>\n <li>\n Able and willing to provide adequate locator information for study retention purposes, as defined by local standard operating procedures</li>\n <li>\n Adequate renal function, defined by creatinine clearance ≥ 60 ml/min estimated by the Cockcroft Creatinine Clearance Formula AND serum creatinine level of ≤ 1.3 mg/dL for men / ≤1.1 mg/dL for women, measured within 56 days of enrollment</li>\n <li>\n Adequate hepatic function, defined by total bilirubin ≤1.5x upper limit of normal AND hepatic transaminases (ALT and AST) <2x upper limit of normal, measured within 56 days of enrollment</li>\n <li>\n Adequate hematologic function, defined by absolute neutrophil count >1,300/mm3, platelets >125,000/mm3, and hemoglobin >11 g/dL, measured within 56 days of enrollment</li>\n <li>\n Not infected with HBV, as determined by a negative hepatitis B surface antigen test, further defined in Appendix VI Note: Potential partner (HIV-1 uninfected) participants who do not meet the renal, hepatic, and/or hematologic inclusion criteria at screening will be allowed to repeat the screening process one additional time. The rescreening process can occur any time >28 days after the initial screening labs were obtained. All other eligibility criteria for these potential participants (as well as all eligibility criteria for the corresponding index participant) must be met for these individuals to be eligible to enroll.</li>\n </ol>\n</div>\n\n Index (HIV-1 Infected) Participants\n\n Potential index (HIV-1 infected) participants must meet the following criteria (by self-report, unless otherwise indicated) in order to be eligible for inclusion in the study:\n<ul>\n <li>\n Of legal age to provide independent informed consent for research per local regulations and guidelines.</li>\n <li>\n Able and willing to provide written informed consent to be screened for and to take part in the study.</li>\n <li>\n Note: Index participants who are not willing to provide genital tract specimens for HIV-1 viral load quantification but who are willing to undergo all other study procedures will be considered eligible for inclusion in the study.</li>\n <li>\n Part of a heterosexual couple in which one partner meets the study eligibility criteria for index (HIV-1 infected) participants and the other partner meets the study eligibility criteria for partner (HIV-1 uninfected) participants, including the following criteria for the couple:</li>\n <li>\n are partners who are sexually active (defined as having had vaginal intercourse with the partner [HIV-1 uninfected] participant at least 6 times in the last three months)</li>\n <li>\n plan to remain in the relationship for the study period</li>\n</ul>\n<div>\n </div>\n<div>\n Each study site will develop appropriate criteria for determining whether a couple is likely to remain in the relationship (i.e., married, duration of partnership, cohabitation, have children).</div>\n<div>\n </div>\n<ul>\n <li>\n HIV-1 infected based on positive EIA.</li>\n <li>\n CD4 cell count ≥250 cells/mm3 and not otherwise meeting national guidelines for initiation of antiretroviral therapy.</li>\n <li>\n No history of any clinical AIDS-defining diagnoses.</li>\n <li>\n Able and willing to provide adequate locator information for study retention purposes, as defined by local standard operating procedures.</li>\n</ul>\n
 principal_exclusion_criteria<div>\n Potential partner (HIV-1 uninfected) participants who meet any of the following criteria (by self-report, unless otherwise indicated) will be excluded from the study:</div>\n<div>\n </div>\n<ul>\n <li>\n Current pregnancy, or planning to become pregnant during the study period</li>\n <li>\n Current breastfeeding</li>\n</ul>\n<div>\n <ul>\n <li>\n Must not be currently enrolled in another HIV-1 vaccine or prevention trial.</li>\n <li>\n Known plans to re-locate or travel away from the study site for more than two consecutive months during the study period.</li>\n <li>\n Repeated positive (≥1+) urine dipstick tests for glycosuria or proteinuria. Participants with definite evidence of glucose and/or protein in their urine will not be eligible. If a urine dipstick is positive for either glucose and/or protein at the first screening visit, a second urine sample will be tested.</li>\n <li>\n Active and serious infections, including active tuberculosis infection or osteomyelitis and all infections requiring parenteral antibiotic therapy; active clinically significant medical problems including cardiac disease (e.g., symptoms of ischemia, congestive heart failure or arrhythmia), pulmonary disease (steroid dependent chronic obstructive pulmonary disease), diabetes requiring hypoglycemic medication; and previously diagnosed malignancy expected to require further treatment.</li>\n <li>\n Note: Enrollment procedures should be delayed in the case of a febrile illness (e.g., malaria) until the potential participant has been treated and recovered.</li>\n <li>\n History of pathological bone fractures not related to trauma</li>\n <li>\n Receiving ongoing therapy with any of the following: antiretroviral therapy (ART), including nucleoside analogs, nonnucleoside reverse transcriptase inhibitors, protease inhibitors or investigational antiretroviral agents, interferon (alpha, beta, or gamma) or interleukin (e.g., IL-2) therapy, metformin, aminoglycoside antibiotics, amphotericin B, cidofovir, systemic chemotherapeutic agents, other agents with significant nephrotoxic potential, other agents that may inhibit or compete for elimination via active renal tubular secretion (e.g., probenecid), and/or other investigational agents</li>\n <li>\n At enrollment, has any other condition that, based on the opinion of the investigator or designee, would preclude provision of informed consent; make participation in the study unsafe; complicate interpretation of study outcome data; or otherwise interfere with achieving the study objectives (including, for couples previously enrolled in the Partners in Prevention HSV/HIV Transmission Trial, having more than 2 missed visits or more than 2 visits outside the visit window)</li>\n </ul>\n</div>\n\n Index (HIV-1 Infected) Participants\n\n Potential index (HIV-1 infected) participants who meet any of theParallel Comparison of Tenofovir and Emtricitabine/tenofovir Pre-Exposure Prophylaxis to\n<ul>\n <li>\n Prevent HIV-1 Acquisition within HIV-1 Discordant Couples</li>\n <li>\n following criteria (by self-report, unless otherwise indicated) will be excluded from the study:</li>\n <li>\n Current use of antiretroviral therapy</li>\n <li>\n Currently enrolled in another HIV-1 treatment trial</li>\n <li>\n At enrollment, has any other condition that, based on the opinion of the investigator or designee, would preclude provision of informed consent; make participation in the study unsafe; complicate interpretation of study outcome data; or otherwise interfere with achieving the study objectives (including, for couples previously enrolled in the Partners in Prevention HSV/HIV Transmission Trial, having more than 2 missed visits or more than 2 visits outside the visit window)</li>\n <li>\n Note: Current pregnancy in the potential index (HIV-1 infected) participant is not an exclusion criterion for this study. Pregnant index partners will be referred to services for antenatal care and prevention of mother-to-child transmission of HIV-1, or treated at the study site, depending on the referral structure for the site.</li>\n <li>\n Note: Current breastfeeding in the potential index (HIV-1 infected) participant is not an exclusion criterion for this study. HIV-1 infected women who are breastfeeding will be counseled on site or referred to prevention of mother-to-child transmission programs to receive information on HIV-1 transmission risks associated with breastfeeding, in accordance with WHO and national recommendations concerning breastfeeding by HIV-1 infected women in developing country settings.</li>\n</ul>\n
 primary_end_points<ol>\n <li>\n HIV-1 seroconversion</li>\n <li>\n AEs among HIV-1 uninfected partners</li>\n</ol>\n
 scope_diagnosis0
 scope_prophylaxis1
 scope_therapy0
 scope_safety1
 scope_efficacy1
 scope_pharmacokinetic0
 scope_pharmacodynamic0
 scope_bioequivalence0
 scope_dose_response0
 scope_pharmacogenetic0
 scope_pharmacogenomic0
 scope_pharmacoecomomic0
 scope_others0
 scope_others_specify
 trial_human_pharmacology0
 trial_administration_humans0
 trial_bioequivalence_study0
 trial_other0
 trial_other_specify
 trial_therapeutic_exploratory0
 trial_therapeutic_confirmatory1
 trial_therapeutic_use0
 design_controlledYes
 site_capacity(null)
 staff_numbers\n Thika partners in Prevention, Site has 32 full time clinical trial staff (including physicians, nurses, counsellors, pharmacists).\n\n Principal Investigator: Dr. Nelly R. Mugo MBCHB,MMED,MPH\n\n Study coordinator: Dr. Kenneth Ngure BSc,MPH,MSc,PhD\n\n Lead Physician: Dr. Elizabeth Irungu MBCHB, MPH\n
 other_details_explanation\n Although the HIV-1 epidemic affects many populations in Africa (commercial sex workers, high-risk men employed far from their stable homes, young sexually active individuals), majority of HIV-1 transmissions to adults in Africa occur within stable, heterosexual, HIV-1 discordant couples. HIV-1 uninfected individuals within HIV-1 discordant partnerships are at high risk for HIV acquisition. HIV-1 discordant couples face unique challenges, including concerns over disclosure of HIV-1 status, HIV-1 associated stigma, and fear of domestic violence. In particular, issues regarding conceptionare espedially concerning to HIV-1 discordant couples. Pregnancy rates in Africa are high (commonly 15-20 per 100 person-years), and social and familial pressures to seek pregnancy are strong, making HIV-1 transmission risk especially great for HIV-1 discordant couples, especially interventions that might allow pregnancy to occur safely, are urgently needed.\n\n In the absence of an HIV-1 cure and recognizing the long development timelines for microbicides and vaccines (that might have substantial impacts on the epidemic but are generally agreed to be over a decade away), other prevention strategies must be developed. Biomedical prevention efforts can be classified into two general groups: 1) Anteretroviral or other drug treatments (e.g. suppressive therapy against herpes simplex virus type 2 infection-HSV-2, which may indirectly reduce HIV-1 levels) provided to HIV-1 infected persons to reduce HIV-1 infectiousness and 2) Use of antiretroviral or other interventions for high-risk HIV-1 uninfected persons to reduce HIV-1 susceptibility.\n\n Pre-exposure chemoprophylaxis, or PrEP, in which an HIV-1 uninfected individual at high risk for contracting HIV-1 takes antiretroviral medications to maintain blood and genital drug levels sufficient to prevent HIV-1 acquisition, has been proposed as a novel potential HIV-1 prevention strategy. Tenofovir disoproxil fumarate (TDF) and coformulated Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) have been suggested to be possible safe and effective medications to serve as PrEP. Both TDF and FTC/TDF are medications that are licenced , and are widely used , for the treatment of HIV-1 infection. These medications are potent , have long half-lives (allowing once daily dosing) , achieve high concentrations in genital tract secretions, have high thresholds against development of viral resistance, do not interact with commonly used medications (e.g. hormonal contraceptives , anti tuberculsis medications), and have been shown to be safe and well tolerated when used as HIV-1 therapy. \n\n \n
 other_details_regulatory_notapproved\n None Pending\n
 other_details_regulatory_approved\n 1.KNH/UON-ERC Approved 4 sites in Kenya (Thika, Nairobi, Kisumu and Eldoret)\n\n 2.University of Washington IRB, approved 4 sites in Kenya (Thika, Nairobi, Kisumu and Eldoret)\n
 other_details_regulatory_rejected
 other_details_regulatory_halted
 estimated_duration48 Months
 design_controlled_randomisedYes
 design_controlled_openNo
 design_controlled_single_blindNo
 design_controlled_double_blindYes
 design_controlled_parallel_groupYes
 design_controlled_cross_overNo
 design_controlled_otherNo
 design_controlled_specify
 design_controlled_comparatorPlacebo
 design_controlled_other_medicinalNo
 design_controlled_placeboYes
 design_controlled_medicinal_otherNo
 design_controlled_medicinal_specify
 single_site_member_stateNo
 location_of_area
 single_site_physical_address
 single_site_contact_person
 single_site_telephone
 multiple_sites_member_stateYes
 multiple_countriesYes
 multiple_member_states2
 number_of_sites4
 multi_country_listKENYA\nUGANDA
 data_monitoring_committeeYes
 total_enrolment_per_site500 to 800 couples
 total_participants_worldwide4700
 population_less_than_18_yearsNo
 population_uteroNo
 population_preterm_newbornNo
 population_newbornNo
 population_infant_and_toddlerNo
 population_childrenNo
 population_adolescentNo
 population_above_18Yes
 population_adultYes
 population_elderlyNo
 gender_female1
 gender_male1
 subjects_healthyYes
 subjects_patientsNo
 subjects_vulnerable_populationsYes
 subjects_women_child_bearingYes
 subjects_women_using_contraceptionYes
 subjects_pregnant_womenNo
 subjects_nursing_womenNo
 subjects_emergency_situationNo
 subjects_incapable_consentNo
 subjects_specify
 subjects_othersNo
 subjects_others_specify
 investigator1_given_nameDr. Nelly
 investigator1_middle_nameRwamba
 investigator1_family_nameMugo
 investigator1_qualificationMBCHB, MMED, MPH
 investigator1_professional_address 19865-00202
 investigator1_telephone067-22561, 0723914057
 investigator1_emailRwamba@csrtkenya.org
 organisations_transferred_Yes
 number_participants2000
 notification
 approval_date12-11-2008
 submitted1
 deleted0
 deleted_date(null)
 deactivated0
 date_submitted12-08-2013
 is_child0
 unsubmitted0
 initial_date_submitted(null)
 admin_stopped0
 admin_stopped_reason(null)
 approved2
 approved_reason
 final_report(null)
 implication_results(null)
 quantity_imported(null)
 quantity_dispensed(null)
 quantity_destroyed(null)
 quantity_exported(null)
 balance_site(null)
 final_date(null)
 modified2020-10-09 10:06:18
 created2013-08-08 12:56:45
 total_sites(null)
 ecitizen_invoice(null)
 InvestigatorContact(array)
 0(array)
 id133
 application_id202
 given_nameProf. Connie
 middle_name
 family_nameCelum
 qualificationProfessor of Medicine and Adjunct Professor of Epidemiology
 professional_addressBox 359927 Cabrini Medical Tower, Suite 1300 901 Boren Avenue Seattle, Washington 98104
 telephone(206) 520-3825
 emailccelum@u.washington.edu
 created2013-08-08 13:04:05
 modified2013-08-12 13:45:15
 SiteDetail(array)
 0(array)
 id163
 application_id202
 county_id27
 site_nameKenya- Eldoret
 physical_addressMoi Teaching Referral Hospital Off Nandi Road Eldoret, Kenya
 contact_detailsMoi Teaching Referral Hospital Off Nandi Road Eldoret, Kenya
 contact_personEdwin Were, MBChB, MMed, MPH Moi University Faculty of Health Sciences
 site_capacity(null)
 misc(null)
 created2013-08-08 13:04:05
 modified2013-08-12 13:45:15
 County(array)
 id27
 county_nameUasin Gishu
 created2012-06-15 10:25:15
 modified2012-06-15 10:25:15
 1(array)
 id164
 application_id202
 county_id47
 site_nameKenya â€“ Nairobi
 physical_addressPartners Study EA #3 Woodlands Rd Off Argwings Khodek Rd Hurlingam Nairobi, Kenya
 contact_detailsPartners Study EA #3 Woodlands Rd Off Argwings Khodek Rd Hurlingam Nairobi, Kenya
 contact_personJames Njogu Kiarie, MBChB, MMed, MPH Kenyatta National Hospital/University of Nairobi
 site_capacity(null)
 misc(null)
 created2013-08-08 16:56:39
 modified2013-08-12 13:45:15
 County(array)
 id47
 county_nameNairobi City
 created2012-06-15 10:27:40
 modified2012-06-15 10:27:40
 2(array)
 id165
 application_id202
 county_id42
 site_nameKenya â€“ Kisumu
 physical_addressCIS Project CMR, Kemri-UCSF Building Lumumba Health Center Kisumu, 40100
 contact_detailsCIS Project CMR, Kemri-UCSF Building Lumumba Health Center Kisumu, 40100
 contact_personElizabeth A. Bukusi. MBChB, MMed, MPH, PhD Center for Microbiology Research, KEMRI
 site_capacity(null)
 misc(null)
 created2013-08-08 17:01:47
 modified2013-08-12 13:45:15
 County(array)
 id42
 county_nameKisumu
 created2012-06-15 10:27:02
 modified2012-06-15 10:27:02
 3(array)
 id166
 application_id202
 county_id27
 site_nameKenya â€“ Thika
 physical_addressPartners in Prevention Located between Wemihs VCT and Thika Nursing Home, Section 9 Thika Town, Kenya
 contact_detailsBox 19865-00202
 contact_personNelly Rwamba Mugo, MD, MMed, MPH University of Washington School of Medicine/University of Nairobi
 site_capacity(null)
 misc(null)
 created2013-08-08 17:03:05
 modified2013-08-12 13:45:15
 County(array)
 id27
 county_nameUasin Gishu
 created2012-06-15 10:25:15
 modified2012-06-15 10:25:15
 Sponsor(array)
 0(array)
 id107
 application_id202
 sponsorUniversity of Washington
 sponsor_type(null)
 contact_personDr. Nelly R. Mugo
 addressBox 359927 325 Ninth Avenue Seattle, Washington 98104
 telephone_number067-22561
 fax_number
 cell_number0723914057
 email_addressRwamba@csrtkenya.org
 created2013-08-08 13:04:05
 modified2013-08-12 13:45:15
 4(array)
 Application(array)
 id90
 user_id56
 trial_status_id5
 abstract_of_study\n HIV-1 uninfected individuals within HIV-1 discordant partnerships are at high-risk for HIV-acquisition. The majority of HIV-1 transmissions to adults in Africa occur within stable, HIV-1 discordant couples. Novel strategies to prevent HIV-1 transmission within discordant couples, especially interventions that might allow pregnancy to occur safely, are urgently needed. Pre-exposure chemoprophylaxis, in which an HIV-1 uninfected individual at high risk for contracting HIV-1 takes antiretroviral medications to maintain blood and genital drug levels sufficient to prevent HIV-1 acquisition, has been proposed as a potential HIV-1 prevention strategy. A randomized, blinded, placebo-controlled trial is required to demonstrate if PrEP decreases HIV-1 acquisition and has an acceptable safety profile when given to HIV-1 uninfected individuals within HIV-1 discordant partnerships.\n\n \n
 study_title\n Parallel Comparison of Tenofovir and Emtricitabine/tenofovir Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition within HIV-1 Discordant Couples\n
 laymans_summary\n HIV-1 uninfected individuals within HIV-1 discordant partnerships are at high-risk for HIV-acquisition. The majority of HIV-1 transmissions to adults in Africa occur within stable, HIV-1 discordant couples. Novel strategies to prevent HIV-1 transmission within discordant couples, especially interventions that might allow pregnancy to occur safely, are urgently needed. Pre-exposure chemoprophylaxis, in which an HIV-1 uninfected individual at high risk for contracting HIV-1 takes antiretroviral medications to maintain blood and genital drug levels sufficient to prevent HIV-1 acquisition, has been proposed as a potential HIV-1 prevention strategy. A randomized, blinded, placebo-controlled trial is required to demonstrate if PrEP decreases HIV-1 acquisition and has an acceptable safety profile when given to HIV-1 uninfected individuals within HIV-1 discordant partnerships.\n
 short_titlePARTNERS PrEP
 protocol_noECCT/08/06/01
 version_noVersion 3.0
 date_of_protocol12-10-2007
 study_drugTenofovir disoproxil fumarate (TDF), Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and matching placebo
 disease_conditionHIV prevention
 product_type_biologicals0
 product_type_proteins0
 product_type_immunologicals0
 product_type_vaccines0
 product_type_hormones0
 product_type_toxoid0
 product_type_chemical1
 product_type_medical_device0
 product_type_chemical_nameTruvada, Tenofovir and matching placebo
 product_type_medical_device_name
 comparatorYes
 comparator_nameTenofovir Disoproxil Fumararte
 comparator_registeredYES
 comparator_countries
 ecct_not_applicable0
 ecct_ref_number
 email_addressebukusi@rctp.or.ke
 applicant_covering_letter1
 applicant_protocol1
 applicant_patient_information1
 applicant_investigators_brochure1
 applicant_investigators_cv1
 applicant_signed_declaration1
 applicant_financial_declaration1
 applicant_gmp_certificate1
 applicant_indemnity_cover1
 applicant_opinion_letter1
 applicant_approval_letter0
 applicant_statement1
 applicant_participating_countries0
 applicant_addendum0
 applicant_fees1
 applicant_complete_form(null)
 applicant_impd1
 applicant_prev_data1
 applicant_stability_data1
 applicant_analysis_cert1
 applicant_pictorial_sample1
 applicant_gcp_training1
 applicant_dsmb_charter1
 applicant_detailed_budget1
 applicant_indemnity_pi1
 applicant_practice_license1
 applicant_registration_ctr(null)
 applicant_pan_african1
 applicant_hard_copies(null)
 applicant_signed_checklist1
 statistical_analysis_plan(null)
 applicant_contractual_agreement(null)
 declaration_applicantDr. Stella Njuguna
 declaration_date104-04-2013
 declaration_principal_investigatorDr. Elizabeth Bukusi
 declaration_date204-04-2013
 placebo_presentYes
 study_objectives\n • To determine if once-daily, oral PrEP with TDF or FTC/TDF provides additional protective benefit in preventing HIV-1 acquisition among HIV-1 uninfected persons within heterosexual HIV-1 discordant couples who are also receiving standard prevention interventions\n\n . • To assess the safety of daily PrEP using TDF or FTC/TDF by comparing rates of adverse events (AEs) among HIV-1 uninfected individuals randomized to TDF or FTC/TDF PrEP to those randomized to placebo.\n
 principal_inclusion_criteria\n Partner (HIV-1 Uninfected) Participants \n Inclusion Criteria \n Potential partner (HIV-1 uninfected) participants must meet the following criteria (by self-report, unless otherwise indicated) in order to be eligible for inclusion in the study: \n • Of legal age to provide independent informed consent for research per local regulations and guidelines \n • Age ≥18 and ≤65\n\n Able and willing to provide written informed consent to be screened for and to take part in the study\n\n • Part of a heterosexual couple in which one partner meets the study eligibility criteria for index (HIV-1 infected) participants and the other partner meets the study eligibility criteria for partner (HIV-1 uninfected) participants, including the following criteria for the couple: \n • \n are partners who are sexually active (defined as having had vaginal intercourse with the partner [HIV-1 uninfected] participant at least 6 times in the last three months) \n •plan to remain in the relationship for the duration of the study period. \n HIV-1 uninfected based on parallel negative HIV-1 rapid tests, both at study screening and at the enrollment visit \n •Able and willing to provide adequate locator information for study retention purposes, as defined by local standard operating procedures \n •Adequate renal function, defined by creatinine clearance ≥ 60 ml/min estimated by the Cockcroft Creatinine Clearance Formula AND serum creatinine level of ≤ 1.3 mg/dL for men / ≤1.1 mg/dL for women, measured within 56 days of enrollment \n • Adequate hepatic function, defined by total bilirubin ≤1.5x upper limit of normal AND hepatic transaminases (ALT and AST) <2x upper limit of normal, measured within 56 days of enrollment \n • Adequate hematologic function, defined by absolute neutrophil count >1,300/mm3, platelets >125,000/mm3, and hemoglobin >11 g/dL, measured within 56 days of enrollment\n\n Not infected with HBV, as determined by a negative hepatitis B surface antigen test\n\n Index (HIV-1 Infected) Participants\n\n Of legal age to provide independent informed consent for research per local regulations and guidelines. \n • Able and willing to provide written informed consent to be screened for and to take part in the study.\n\n Part of a heterosexual couple in which one partner meets the study eligibility criteria for index (HIV-1 infected) participants and the other partner meets the study eligibility criteria for partner (HIV-1 uninfected) participants, including the following criteria for the couple: \n • \n are partners who are sexually active (defined as having had vaginal intercourse with the partner [HIV-1 uninfected] participant at least 6 times in the last three months) \n • \n plan to remain in the relationship for the study period \n Each study site will develop appropriate criteria for determining whether a couple is likely to remain in the relationship (i.e., married, duration of partnership, cohabitation, have children). \n • \n HIV-1 infected based on positive EIA. \n • \n CD4 cell count ≥250 cells/mm3 and not otherwise meeting national guidelines for initiation of antiretroviral therapy. \n • \n No history of any clinical AIDS-defining diagnoses. \n • \n Able and willing to provide adequate locator information for study retention purposes, as defined by loc\n\n \n\n \n
 principal_exclusion_criteria\n HIV infected partner\n\n Current use of antiretroviral therapy \n • \n Currently enrolled in another HIV-1 treatment trial \n • \n At enrollment, has any other condition that, based on the opinion of the investigator or designee, would preclude provision of informed consent; make participation in the study unsafe; complicate interpretation of study outcome data; or otherwise interfere with achieving the study objectives\n\n HIV uninfected Partner\n\n Current pregnancy, or planning to become pregnant during the study period \n • \n Current breastfeeding\n\n Must not be currently enrolled in another HIV-1 vaccine or prevention trial. \n • \n Known plans to re-locate or travel away from the study site for more than two consecutive months during the study period. \n • \n Repeated positive (≥1+) urine dipstick tests for glycosuria or proteinuria. Participants with definite evidence of glucose and/or protein in their urine will not be eligible. If a urine dipstick is positive for either glucose and/or protein at the first screening visit, a second urine sample will be tested. \n • \n Active and serious infections, including active tuberculosis infection or osteomyelitis and all infections requiring parenteral antibiotic therapy; active clinically significant medical problems including cardiac disease (e.g., symptoms of ischemia, congestive heart failure or arrhythmia), pulmonary disease (steroid dependent chronic obstructive pulmonary disease), diabetes requiring hypoglycemic medication; and previously diagnosed malignancy expected to require further treatment.History of pathological bone fractures not related to trauma \n • \n Receiving ongoing therapy with any of the following: antiretroviral therapy (ART), including nucleoside analogs, nonnucleoside reverse transcriptase inhibitors, protease inhibitors or investigational antiretroviral agents, interferon (alpha, beta, or gamma) or interleukin (e.g., IL-2) therapy, metformin, aminoglycoside antibiotics, amphotericin B, cidofovir, systemic chemotherapeutic agents, other agents with significant nephrotoxic potential, other agents that may inhibit or compete for elimination via active renal tubular secretion (e.g., probenecid), and/or other investigational agents \n • \n At enrollment, has any other condition that, based on the opinion of the investigator or designee, would preclude provision of informed consent; make participation in the study unsafe; complicate interpretation of study outcome data\n\n \n\n \n
 primary_end_points\n HIV-1 seroconversion and AEs among HIV-1 uninfected partners\n
 scope_diagnosis1
 scope_prophylaxis1
 scope_therapy0
 scope_safety1
 scope_efficacy1
 scope_pharmacokinetic0
 scope_pharmacodynamic0
 scope_bioequivalence0
 scope_dose_response0
 scope_pharmacogenetic0
 scope_pharmacogenomic0
 scope_pharmacoecomomic0
 scope_others0
 scope_others_specify
 trial_human_pharmacology0
 trial_administration_humans0
 trial_bioequivalence_study0
 trial_other0
 trial_other_specify
 trial_therapeutic_exploratory0
 trial_therapeutic_confirmatory1
 trial_therapeutic_use0
 design_controlledYes
 site_capacity(null)
 staff_numbers\n The Research, Care Training, and Program (RCTP) was established by leading medical researchers from the Kenya Medical Research Institute (KEMRI), the University of Nairobi (UoN) and University of California San Francisco (UCSF) in 1994 to facilitate collaborative research on STIs including HIV prevention, care and treatment. RCTP is currently co-headed by Drs. Elizabeth Bukusi (Deputy Director Research and Training, KEMRI) and Craig Cohen (Associate Professor of Medicine, UCSF). RCTP has three complementary arms namely: research, care and training. the project has a wealth of expertise in research.\n\n The research arm of RCTP currently has several projects on-going, which include: female microbicide studies funded by International Partnership for Microbicide (IPM), a male microbicide study funded by Consortium for National Health Research (CNHR), a pre-exposure prophylaxis study funded by Bill and Melinda Gates Foundation, as well as ANC/HIV and FP/HIV integration studies.\n\n Site Principal Investigator- Dr. Elizabeth Bukusi (MBChB, MMED,MPH,PHD)\n\n Study Cordinator- Josephine Odoyo (RN,MPH)\n\n Laboratory Manager- Raphael Ondondo (Msc)\n\n Data Manager- Bernard Rono (BSc -Statistics)\n\n Clinical Manager- Imeldah Wakhungu (dip Clinical Medicine)\n\n Pharmacy Manager- Dr. Angeline Achoka (BPharm)\n\n Finance and Administrative Manager- Alfred Obiero (MBA)\n\n QA/QC Manager- Jackson Achando (BSc Nursing, MA-Project Development)\n\n \n
 other_details_explanation\n HIV-1 uninfected individuals within HIV-1 discordant partnerships are at high-risk for HIV-acquisition. The majority of HIV-1 transmissions to adults in Africa occur within stable, HIV-1 discordant couples. Novel strategies to prevent HIV-1 transmission within discordant couples, especially interventions that might allow pregnancy to occur safely, are urgently needed. Pre-exposure chemoprophylaxis, in which an HIV-1 uninfected individual at high risk for contracting HIV-1 takes antiretroviral medications to maintain blood and genital drug levels sufficient to prevent HIV-1 acquisition, has been proposed as a potential HIV-1 prevention strategy.\n
 other_details_regulatory_notapproved\n None\n
 other_details_regulatory_approved\n KEMRI ERC- 9th May 2008, apporved the Kisumu Site study\n
 other_details_regulatory_rejected\n Not Applicable\n
 other_details_regulatory_halted\n Efficacy was realised and the participants on Placebo were randomised to either Truvada or Tenofovir. This was a directive from the Data Safety and Monitoring Board of the PrEP study in July 2011.\n
 estimated_duration4 years
 design_controlled_randomisedYes
 design_controlled_openNo
 design_controlled_single_blindNo
 design_controlled_double_blindYes
 design_controlled_parallel_groupYes
 design_controlled_cross_overNo
 design_controlled_otherNo
 design_controlled_specify
 design_controlled_comparatormatched placebo
 design_controlled_other_medicinalNo
 design_controlled_placeboYes
 design_controlled_medicinal_otherNo
 design_controlled_medicinal_specify
 single_site_member_stateNo
 location_of_area
 single_site_physical_address
 single_site_contact_person
 single_site_telephone
 multiple_sites_member_stateYes
 multiple_countriesYes
 multiple_member_states2
 number_of_sites4
 multi_country_listUganda
 data_monitoring_committeeYes
 total_enrolment_per_site500-800 couples from each participating study site. In Kenya, there are four study sites- Kisumu, Thika, Eldoret and Nairobi
 total_participants_worldwide3900 HIV -1 discordant couples
 population_less_than_18_yearsNo
 population_uteroNo
 population_preterm_newbornNo
 population_newbornNo
 population_infant_and_toddlerNo
 population_childrenNo
 population_adolescentNo
 population_above_18Yes
 population_adultNo
 population_elderlyNo
 gender_female1
 gender_male1
 subjects_healthyNo
 subjects_patientsNo
 subjects_vulnerable_populationsNo
 subjects_women_child_bearingNo
 subjects_women_using_contraceptionNo
 subjects_pregnant_womenNo
 subjects_nursing_womenNo
 subjects_emergency_situationNo
 subjects_incapable_consentNo
 subjects_specify
 subjects_othersNo
 subjects_others_specify
 investigator1_given_nameConnie
 investigator1_middle_name
 investigator1_family_nameCelum
 investigator1_qualificationMD, MPH
 investigator1_professional_addressUniversity of Washington Box 359927 Cabrini Medical Tower, Suite 1300 901 Boren Avenue Seattle, Washington 98104
 investigator1_telephone(206) 520-3825
 investigator1_emailccelum@uw.edu
 organisations_transferred_No
 number_participants500-800 couples from each participating study site. In Kenya, there are four study sites- Kisumu, Thika, Eldoret and Nairobi
 notification
 approval_date30-07-2008
 submitted1
 deleted0
 deleted_date(null)
 deactivated0
 date_submitted23-06-2020
 is_child0
 unsubmitted0
 initial_date_submitted(null)
 admin_stopped0
 admin_stopped_reason(null)
 approved2
 approved_reason
 final_report(null)
 implication_results(null)
 quantity_imported(null)
 quantity_dispensed(null)
 quantity_destroyed(null)
 quantity_exported(null)
 balance_site(null)
 final_date(null)
 modified2020-06-23 10:03:43
 created2013-04-04 12:23:32
 total_sites(null)
 ecitizen_invoice(null)
 InvestigatorContact(array)
 0(array)
 id56
 application_id90
 given_nameElizabeth Anne
 middle_name
 family_nameBukusi
 qualificationMBChB, MMed, MPH, PhD
 professional_addressLumumba Health Center Kisumu, 614-40100 Kenya
 telephone0733617503
 emailebukusi@rctp.or.ke
 created2013-04-04 12:25:31
 modified2020-06-23 10:03:43
 SiteDetail(array)
 0(array)
 id74
 application_id90
 county_id42
 site_nameKisumu site
 physical_addressLumumba Health Centre
 contact_details614-40100 0733617503
 contact_personDr. Elizabeth Bukusi
 site_capacity(null)
 misc(null)
 created2013-04-04 12:25:31
 modified2020-06-23 10:03:43
 County(array)
 id42
 county_nameKisumu
 created2012-06-15 10:27:02
 modified2012-06-15 10:27:02
 Sponsor(array)
 0(array)
 id42
 application_id90
 sponsorUniversity of Washington
 sponsor_typeOthers
 contact_person
 addressUniversity of Washington Box 359927 Cabrini Medical Tower, Suite 1300 901 Boren Avenue Seattle, Washington 98104
 telephone_number (206) 520-3825
 fax_number(206) 520-3831
 cell_number (206) 520-3825
 email_addressccelum@u.washington.edu
 created2013-04-04 12:25:31
 modified2020-06-23 10:03:43
- page_options(array)
 55
 1010
- redir
- $request->data(array)
 Application(array)
 approved1
- $this->validationErrors(array)
 Permission(empty)
 Aro(empty)
 Aco(empty)
 Application(empty)
 User(empty)
 TrialStatus(empty)
 InvestigatorContact(empty)
 Sponsor(empty)
 SiteDetail(empty)
 County(empty)
- Loaded Helpers(array)
 0Html
 1Form
 2Session
 3Text
 4Number
 5SimpleGraph
 6Paginator
 7DebugTimer
 8Toolbar
 9HtmlToolbar
====

Environment

App Constants

Constant	Value
MEDIA	'/var/www/html/ctr/app/webroot/media/'
MEDIA_STATIC	'/var/www/html/ctr/app/webroot/media/static/'
MEDIA_FILTER	'/var/www/html/ctr/app/webroot/media/filter/'
MEDIA_TRANSFER	'/var/www/html/ctr/app/webroot/media/transfer/'
MEDIA_URL	'media/'
MEDIA_STATIC_URL	'media/static/'
MEDIA_FILTER_URL	'media/filter/'
MEDIA_TRANSFER_URL	'media/transfer/'
HTTP_HOST	'ctr.pharmacyboardkenya.org'
HTTP_BASE	'http://ctr.pharmacyboardkenya.org'
HTTP_SELF	'/app/webroot/index.php'
HTTP_URI	'/applications/index/page:90/sort:study_title/direction:asc/approved:1'
CHOWN_PUBLIC	(int) 504
LF	''
NL	''
CR	''
TB	''
BR	' '
WINDOWS	false
FORMAT_DB_DATETIME	'Y-m-d H:i:s'
FORMAT_DB_DATE	'Y-m-d'
FORMAT_DB_TIME	'H:i:s'
DEFAULT_DATETIME	'0000-00-00 00:00:00'
DEFAULT_DATE	'0000-00-00'
DEFAULT_TIME	'00:00:00'
FILES	'/var/www/html/ctr/app/files/'
LOCALE	'/var/www/html/ctr/app/locale/'
CLASS_USER	'User'
VALID_ALPHA	'/^[a-zA-Z]+$/'
VALID_ALPHA_UNDERSCORES	'/^[a-zA-Z_]+$/'
VALID_ALPHA_MINUS_UNDERSCORES	'/^[a-zA-Z_-]+$/'
VALID_ALPHA_WHITESPACES	'/^[a-zA-Z ]+$/'
VALID_ALPHANUMERIC_UNDERSCORES	'/^[\da-zA-Z_]+$/'
VALID_ALPHANUMERIC_MINUS_UNDERSCORES	'/^[\da-zA-Z_-]+$/'
VALID_ALPHANUMERIC_WHITESPACES	'/^[\da-zA-Z ]+$/'
VALID_ALPHANUMERIC_WHITESPACES_UNDERSCORES	'/^[\da-zA-Z _]+$/'
VALID_NUMERIC_UNDERSCORES	'/^[\d_]+$/'
VALID_NUMERIC_WHITESPACES	'/^[\d ]+$/'
VALID_NUMERIC_WHITESPACES_UNDERSCORES	'/^[\d _]+$/'
VALID_INTEGERS	'/^[\d]+$/'
FORMAT_NICE_YMDHMS	'd.m.Y, H:i:s'
FORMAT_NICE_YMDHM	'd.m.Y, H:i'
FORMAT_NICE_YM	'm.Y'
FORMAT_NICE_YMD	'd.m.Y'
FORMAT_NICE_MD	'd.m.'
FORMAT_NICE_D	'd'
FORMAT_NICE_W_NUM	'w'
FORMAT_NICE_W_ABBR	'D'
FORMAT_NICE_W_FULL	'l'
FORMAT_NICE_M	'm'
FORMAT_NICE_M_ABBR	'M'
FORMAT_NICE_M_FULL	'F'
FORMAT_NICE_Y_ABBR	'y'
FORMAT_NICE_Y	'Y'
FORMAT_NICE_HM	'H:i'
FORMAT_NICE_HMS	'H:i:s'
FORMAT_LOCAL_WA_YMDHMS	'%a, %d.%m.%Y, %H:%M:%S'
FORMAT_LOCAL_WF_YMDHMS	'%A, %d.%m.%Y, %H:%M:%S'
FORMAT_LOCAL_WA_YMDHM	'%a, %d.%m.%Y, %H:%M'
FORMAT_LOCAL_WF_YMDHM	'%A, %d.%m.%Y, %H:%M'
FORMAT_LOCAL_YMDHMS	'%d.%m.%Y, %H:%M:%S'
FORMAT_LOCAL_YMDHM	'%d.%m.%Y, %H:%M'
FORMAT_LOCAL_YMD	'%d.%m.%Y'
FORMAT_LOCAL_MD	'%d.%m.'
FORMAT_LOCAL_D	'%d'
FORMAT_LOCAL_W_NUM	'%w'
FORMAT_LOCAL_W_ABBR	'%a'
FORMAT_LOCAL_W_FULL	'%A'
FORMAT_LOCAL_M	'%m'
FORMAT_LOCAL_M_ABBR	'%b'
FORMAT_LOCAL_M_FULL	'%B'
FORMAT_LOCAL_Y_ABBR	'%y'
FORMAT_LOCAL_YMS_ABBR	'%d.%m.%y'
FORMAT_LOCAL_Y	'%Y'
FORMAT_LOCAL_H	'%H'
FORMAT_LOCAL_S	'%S'
FORMAT_LOCAL_HM	'%H:%M'
FORMAT_LOCAL_HMS	'%H:%M:%S'
CHAR_LESS	'<'
CHAR_GREATER	'>'
CHAR_QUOTE	'"'
CHAR_APOSTROPHE	'''
CHAR_ARROWS	'»'
CHAR_ARROWS_R	'»'
CHAR_ARROWS_L	'«'
CHAR_AVERAGE	'Ø'
CHAR_INFIN	'∞'
CHAR_MILL	'‰'
CHAR_PLUSMN	'±'
CHAR_HELLIP	'…'
CHAR_CIRCA	'≈'
CHAR_CHECKBOX_EMPTY	'☐]'
CHAR_CHECKBOX_MAKRED	'☑'
CHAR_CHECKMARK	'✓'
CHAR_CHECKMARK_BOLD	'✔'
CHAR_BALLOT	'✗'
CHAR_BALLOT_BOLD	'✘'
CHAR_ABOUT	'≈'
CHAR_RPIME	'′'
CHAR_DOUBLE_RPIME	'″'

CakePHP Constants

Constant	Value
APP	'/var/www/html/ctr/app/'
APP_DIR	'app'
APPLIBS	'/var/www/html/ctr/app/Lib/'
CACHE	'/var/www/html/ctr/app/tmp/cache/'
CAKE	'/var/www/html/ctr/lib/Cake/'
CAKE_CORE_INCLUDE_PATH	'/var/www/html/ctr/lib'
CORE_PATH	'/var/www/html/ctr/lib/'
CAKE_VERSION	'2.2.2'
CSS	'/var/www/html/ctr/app/webroot/css/'
CSS_URL	'css/'
DS	'/'
FULL_BASE_URL	'https://ctr.pharmacyboardkenya.org'
IMAGES	'/var/www/html/ctr/app/webroot/img/'
IMAGES_URL	'img/'
JS	'/var/www/html/ctr/app/webroot/js/'
JS_URL	'js/'
LOGS	'/var/www/html/ctr/app/tmp/logs/'
ROOT	'/var/www/html/ctr'
TESTS	'/var/www/html/ctr/app/Test/'
TMP	'/var/www/html/ctr/app/tmp/'
VENDORS	'/var/www/html/ctr/vendors/'
WEBROOT_DIR	'webroot'
WWW_ROOT	'/var/www/html/ctr/app/webroot/'

PHP Environment

Environment Variable	Value
Php Version	'5.6.40-81+ubuntu20.04.1+deb.sury.org+1'
Redirect Redirect Https	'on'
Redirect Redirect Ssl Tls Sni	'ctr.pharmacyboardkenya.org'
Redirect Redirect Status	'200'
Redirect Https	'on'
Redirect Ssl Tls Sni	'ctr.pharmacyboardkenya.org'
Redirect Status	'200'
Https	'on'
Ssl Tls Sni	'ctr.pharmacyboardkenya.org'
Http Accept	'/'
Http User Agent	'Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)'
Http Accept Encoding	'gzip, br, zstd, deflate'
Http Host	'ctr.pharmacyboardkenya.org'
Path	'/usr/local/sbin:/usr/local/bin:/usr/sbin:/usr/bin:/sbin:/bin:/snap/bin'
Server Signature	' Apache/2.4.41 (Ubuntu) Server at ctr.pharmacyboardkenya.org Port 443 '
Server Software	'Apache/2.4.41 (Ubuntu)'
Server Name	'ctr.pharmacyboardkenya.org'
Server Addr	'192.168.10.21'
Server Port	'443'
Remote Addr	'3.133.144.147'
Document Root	'/var/www/html/ctr'
Request Scheme	'https'
Context Prefix	''
Context Document Root	'/var/www/html/ctr'
Server Admin	'webmaster@localhost'
Script Filename	'/var/www/html/ctr/app/webroot/index.php'
Remote Port	'28765'
Redirect Url	'/app/webroot/applications/index/page:90/sort:study_title/direction:asc/approved:1'
Gateway Interface	'CGI/1.1'
Server Protocol	'HTTP/1.1'
Request Method	'GET'
Query String	''
Request Uri	'/applications/index/page:90/sort:study_title/direction:asc/approved:1'
Script Name	'/app/webroot/index.php'
Php Self	'/app/webroot/index.php'
Request Time Float	(float) 1746125158.302
Request Time	(int) 1746125158

====

Include
+
Included Files

Include Paths
- 0/var/www/html/ctr/app/Plugin/Media/Lib/mm/src
- 1/var/www/html/ctr/lib
- 3/usr/share/php
- 4-> /var/www/html/ctr/lib/Cake/
Included Files
- core(array)
  Behavior(array)
  0CORE/Model/Behavior/TreeBehavior.php
  1CORE/Model/Behavior/ContainableBehavior.php
  2CORE/Model/Behavior/AclBehavior.php
  Cache(array)
  0CORE/Cache/Cache.php
  1CORE/Cache/Engine/FileEngine.php
  2CORE/Cache/CacheEngine.php
  Component(array)
  0CORE/Controller/Component/AclComponent.php
  1CORE/Controller/Component/Acl/DbAcl.php
  2CORE/Controller/Component/Acl/AclInterface.php
  3CORE/Controller/Component/AuthComponent.php
  4CORE/Controller/Component/RequestHandlerComponent.php
  5CORE/Controller/Component/SessionComponent.php
  6CORE/Controller/Component/PaginatorComponent.php
  Config(array)
  0CORE/Config/routes.php
  1CORE/Config/config.php
  Controller(array)
  0CORE/Controller/Controller.php
  1CORE/Controller/ComponentCollection.php
  2CORE/Controller/Component.php
  Datasource(array)
  0CORE/Model/Datasource/CakeSession.php
  1CORE/Model/Datasource/Database/Mysql.php
  2CORE/Model/Datasource/DboSource.php
  3CORE/Model/Datasource/DataSource.php
  Error(array)
  0CORE/Error/exceptions.php
  1CORE/Error/ErrorHandler.php
  I18n(array)
  0CORE/I18n/I18n.php
  1CORE/I18n/L10n.php
  Log(array)
  0CORE/Log/CakeLog.php
  1CORE/Log/LogEngineCollection.php
  2CORE/Log/Engine/FileLog.php
  3CORE/Log/Engine/BaseLog.php
  4CORE/Log/CakeLogInterface.php
  Model(array)
  0CORE/Model/ConnectionManager.php
  1CORE/Model/Permission.php
  2CORE/Model/Model.php
  3CORE/Model/BehaviorCollection.php
  4CORE/Model/Aro.php
  5CORE/Model/AclNode.php
  6CORE/Model/Aco.php
  7CORE/Model/ModelBehavior.php
  Network(array)
  0CORE/Network/CakeRequest.php
  1CORE/Network/CakeResponse.php
  Other(array)
  0CORE/bootstrap.php
  1CORE/basics.php
  2CORE/Core/App.php
  3CORE/Core/Configure.php
  4CORE/Core/CakePlugin.php
  5CORE/Event/CakeEventListener.php
  6CORE/Event/CakeEvent.php
  7CORE/Event/CakeEventManager.php
  8CORE/Core/Object.php
  Routing(array)
  0CORE/Routing/Dispatcher.php
  1CORE/Routing/Filter/AssetDispatcher.php
  2CORE/Routing/DispatcherFilter.php
  3CORE/Routing/Filter/CacheDispatcher.php
  4CORE/Routing/Router.php
  5CORE/Routing/Route/CakeRoute.php
  6CORE/Routing/Route/PluginShortRoute.php
  Utility(array)
  0CORE/Utility/Hash.php
  1CORE/Utility/Inflector.php
  2CORE/Utility/ObjectCollection.php
  3CORE/Utility/Debugger.php
  4CORE/Utility/String.php
  5CORE/Utility/ClassRegistry.php
  6CORE/Utility/Set.php
  7CORE/Utility/Sanitize.php
  View(array)
  0CORE/View/HelperCollection.php
- app(array)
  Behavior(array)
  0APP/Model/Behavior/SoftDeleteBehavior.php
  Config(array)
  0APP/Config/core.php
  1APP/Config/bootstrap.php
  2APP/Config/routes.php
  3APP/Config/database.php
  Controller(array)
  0APP/Controller/ApplicationsController.php
  1APP/Controller/AppController.php
  Model(array)
  0APP/Model/AppModel.php
  1APP/Model/Application.php
  2APP/Model/User.php
  3APP/Model/TrialStatus.php
  4APP/Model/InvestigatorContact.php
  5APP/Model/Sponsor.php
  6APP/Model/SiteDetail.php
  7APP/Model/County.php
  Other(array)
  0APP/webroot/index.php
- plugins(array)
  CakePdf(array)
  Config(array)
  0CakePdf/Config/bootstrap.php
  1CakePdf/Config/routes.php
  CakeResque(array)
  Config(array)
  0CakeResque/Config/bootstrap.php
  Plugin(array)
  0CakeResque/Lib/CakeResque.php
  1CakeResque/vendor/kamisama/php-resque-ex/lib/Resque.php
  2CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Event.php
  3CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Exception.php
  DebugKit(array)
  Component(array)
  0DebugKit/Controller/Component/ToolbarComponent.php
  Plugin(array)
  0DebugKit/Lib/DebugMemory.php
  1DebugKit/Lib/Panel/HistoryPanel.php
  2DebugKit/Lib/DebugPanel.php
  3DebugKit/Lib/Panel/SessionPanel.php
  4DebugKit/Lib/Panel/RequestPanel.php
  5DebugKit/Lib/Panel/SqlLogPanel.php
  6DebugKit/Lib/Panel/TimerPanel.php
  7DebugKit/Lib/Panel/LogPanel.php
  8DebugKit/Lib/Log/Engine/DebugKitLog.php
  9DebugKit/Lib/Panel/VariablesPanel.php
  10DebugKit/Lib/Panel/EnvironmentPanel.php
  11DebugKit/Lib/Panel/IncludePanel.php
  12DebugKit/Lib/DebugTimer.php
  Media(array)
  Config(array)
  0Media/Config/bootstrap.php
  Plugin(array)
  0Media/Lib/mm/src/Mime/Type.php
  1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
  2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
  3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
  4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
  5Media/Lib/mm/src/Media/Process.php
  6Media/Lib/mm/src/Media/Info.php
  Search(array)
  Component(array)
  0Search/Controller/Component/PrgComponent.php
  Behavior(array)
  0Search/Model/Behavior/SearchableBehavior.php
  Shim(array)
  Config(array)
  0Shim/Config/bootstrap.php
  Tools(array)
  Config(array)
  0Tools/Config/bootstrap.php
====

Clinical Trial Applications: Filter, Search, and view applications {lang: 'en-GB'}

Request History

Session

Request

Cake Params

Post data

Query string

Cookie

Current Route

Sql Logs

default

Total Time: 135 ms Total Queries: 19 queries

Query Explain:

Memory

Timers

Logs

View Variables

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

Included Files

Clinical Trial Applications: Filter, Search, and view applications

Total Time: 135 ms
Total Queries: 19 queries