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• applications(array)
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    • Application(array)
      • id1007
      • user_id480
      • trial_status_id5
      • abstract_of_study<p>\n SARS-CoV-2, the cause of the coronavirus disease 2019 (COVID-19) pandemic, has evolved into new strains that are also referred to as ‘variants.’ A rapidly spreading variant called B.1.351, first identified in South Africa has now spread to Kenya. This variant is considered a ‘variant of concern’ because it is more transmissible than the original strain and because some vaccines appear to have reduced protection against this strain of SARS-CoV-2. In vitro, the B.1.351 variant’s mutations reduce efficiency of neutralizing antibodies induced by the Moderna mRNA (original Wuhan strain) vaccine. It is unknown whether this in vitro finding also reduces the clinical efficacy of the vaccine. We aim to test the safety and efficacy of Moderna’s two-dose mRNA vaccine in 14,000 participants recruited from eight African countries; 300 will be recruited in Kisumu. Participants will be over age 40 years with at least one comorbidity associated with severe COVID-19, or over 18 years of age and pregnant, or over 18 years of age and HIV-infected. The objectives of this randomized, double-blind, immediate versus deferred vaccination trial with cross-over at approximately three months are to assess vaccine efficacy to prevent virologically confirmed or virologically unconfirmed symptomatic COVID-19. All participants will receive the vaccine. The ratio of participants in immediate and deferred arms is 1:1. CDC Africa encouraged testing various vaccines in the continent to be sure they are efficacious. The World Health Organization has recently listed the Moderna vaccine for emergency use listing. To date, mRNA vaccines have hardly been deployed in the African continent. If this trial is successful, it will provide a new weapon to control the pandemic in Africa and yield critical information on its efficacy against the new variants emerging in Kenya, including the B.1.351 variant of concern.</p>\n
      • study_title<p>\n Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions with SARS-CoV-2 Variants of Concern</p>\n
      • laymans_summary<p>\n Since 12 March 2020 when the first COVID-19 case was confirmed in Kenya, as at 26 Mar 2021, a total of 126,170 confirmed cases have been identified and 2,092 people have died yielding a death rate of 1.7 persons per 100 people infected. The mRNA vaccine developed by Moderna and based on the genetic information of the orignal viral strain that originated in Wuhan, China, was proven to be highly efficacious in preventing COVID-19 infections. It received an Emergency Use Authorization by the Food & Drug Administration and is now widely used in the USA but has not been used in the African continent. The Africa CDC has encouraged nations in its continent to test the efficacy and safety of a variety of vaccines in their populations. As SARS-CoV-2 – the virus that causes COVID-19 – spreads around the globe, it is mutating. It changes in response to the different immune responses in different people. It changes to form new variants for example the B1.1.7 variant first discovered in the United Kingdom and the B.1.351, first identified in South Africa. It is therefore important to assess whether the ability of the Moderna mRNA vaccine to prevent Covid 19 will be affected. The Moderna mRNA vaccine contains material from the virus that causes COVID-19 that gives our cells instructions for how to make a harmless protein that is unique to the virus. After our cells make copies of the protein, they destroy the genetic material from the vaccine. Our bodies recognize that the protein should not be there and build T-lymphocytes (a type of white blood cell) and B-lymphocytes that will remember how to fight the virus that causes COVID-19 if we are infected in the future. The B lymphocytes produce substances known as neutralizing antibodies which can stop a virus from infecting the body by affecting how the molecules on the virus’ surface can enter cells in the body. The SARS-CoV-2 South African variant has changes known to reduce how well the neutralizing antibodies produced by the Moderna mRNA vaccine work. At this time, it is not clear whether this can reduce how well the vaccine works and cause widespread vaccine failure. However as mentioned above, the vaccine also triggers formation of T lymphocytes which may provide enough protection. It is also possible that the high amount of neutralizing antibodies produced by the Moderna mRNA vaccine will provide enough protection despite reduced sensitivity of the South African virus. Since the South African variant is present and increasing in the Eastern and Southern African Region, it is important to perform a vaccine efficacy study. The study will assess the clinical impact of the parent mRNA vaccine (i.e., original Wuhan strain) on both moderate and severe disease and death in these regions among adults who are at high risk of severe disease. The study will also carefully examine breakthrough viruses in fully vaccinated individuals. A breakthrough infection is a case of illness in which a vaccinated individual becomes sick from the same illness that the vaccine is meant to prevent. This is important so as to determine whether vaccines need to be tailor made for the different variants of concern or if vaccines need to be modified to accommodate changes for global vaccines, and whether the original vaccine will provide higher protection against severe disease when administered as a booster. (A booster dose is an extra administration of a vaccine after an earlier dose. It is intended to increase immunity after memory against a foreign substance eg. a virus has declined through time). This study will involve people who are at high risk for COVID-19. This trial has an immediate vs. delayed design, eventually immunizing all participants with the vaccine but delaying by three months (at the crossover visit) the immunization of half of participants to assess the efficacy of the mRNA vaccine. Fourteen thousand participants will be recruited from eight African countries, with approximately three hundred from the Kisumu Clinical Research Site. Although a great deal is known about the safety of the Moderna vaccine in the US, this trial will provide an opportunity to test the vaccine’s safety in African populations.</p>\n
      • short_titleCoVPN 3008
      • protocol_noECCT/21/05/07
      • version_no1.0
      • date_of_protocol16-05-2021
      • study_drugCOVID-19 mRNA Vaccine
      • disease_conditionCovid 19
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_nameVaccine
      • comparatorYes
      • comparator_namePlacebo: Sodium Chloride 0.9 % for injection
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresseodipo@kemricdc.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_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • 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_plan1
      • applicant_contractual_agreement1
      • declaration_applicantDr. Grace Mboya
      • declaration_date127-05-2021
      • declaration_principal_investigatorPhilister Madiega
      • declaration_date227-05-2021
      • placebo_presentYes
      • study_objectives<ol start=\"1\">\n <li>\n To assess vaccine efficacy (VE) of COVID-19 mRNA vaccine to prevent virologically-confirmed symptomatic COVID-19 starting 14 days after dose 2 in adults who are at risk of severe COVID-19</li>\n <li>\n To assess vaccine efficacy (VE) of COVID-19 mRNA vaccine to prevent severe COVID-19 starting 14 days after dose 2 in adults who are at risk for severe COVID-19</li>\n <li>\n To assess safety and tolerability of COVID-19 mRNA vaccine in adults who are at risk of severe COVID-19</li>\n</ol>\n
      • principal_inclusion_criteria<p>\n 1.Age ≥ 18 years if volunteer self-reports pregnant OR HIV-positive, OR age ≥ 40 years with ≥ 1 co-morbidity known to be associated with severe COVID-19, for example:</p>\n<p>\n • Hypertension</p>\n<p>\n • Type 2 diabetes mellitus</p>\n<p>\n • Obesity (body mass index [BMI] of 30 kg/m2 or higher but < 40 kg/m2)</p>\n<p>\n • Severe Obesity (BMI ≥ 40 kg/m2</p>\n<p>\n • Heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies</p>\n<p>\n • Chronic kidney disease • COPD (chronic obstructive pulmonary disease)</p>\n<p>\n • Cancer .</p>\n<p>\n 2.Non-HIV immunocompromised state (weakened immune system) or solid organ transplant • Pregnancy Willingness to be followed and remain in the catchment area for the planned duration of the study.</p>\n<p>\n 3. Ability and willingness to provide informed consent.</p>\n<p>\n 4. Willingness to discuss HIV infection risks and willing to receive HIV testing, risk reduction counseling, and appropriate referrals to minimize HIV acquisition, if volunteer is pregnant</p>\n<p>\n 5. Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with demonstration of understanding of all questionnaire items answered incorrectly.</p>\n<p>\n 6. Willing to defer SARS-CoV-2 vaccination until the crossover visit (anticipated at approximately Month 3.5).</p>\n<p>\n 7. Agrees not to enroll in another study of an investigational research agent until the end of the study. Enrollment in studies of investigational research agents for the treatment of COVID-19 is allowed for participants who develop COVID-19 disease. • Sickle cell disease • Smoking</p>\n
      • principal_exclusion_criteria<p>\n 1. Acutely ill 72 hours prior to or at screening. Volunteers meeting this criterion may be rescheduled within the relevant window periods. Participants with minor illnesses can be enrolled at the discretion of the investigator.</p>\n<p>\n 2. History of angioedema or anaphylaxis</p>\n<p>\n 3. Self-reported previous COVID-19 diagnosis</p>\n<p>\n 4. Prior administration of a SARS-CoV-2 vaccine.</p>\n<p>\n 5. Live attenuated vaccines received within 30 days before first vaccination or scheduled within 14/28 days after injection (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever; live attenuated influenza vaccine).</p>\n<p>\n 6. Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B). 7. Blood products, systemic immunoglobulins, or monoclonal antibodies (including against SARS-CoV-2) received within 90 days before first vaccination</p>\n
      • primary_end_points<ol>\n <li>\n COVID-19: Positive result of acute SARS-CoV-2 infection as assessed by nucleic acid amplification testing (NAAT) or antigen testing of a nasal swab whose collection was triggered by a prespecified symptom or symptoms (see footnote 1) in volunteers with no previous COVID-19</li>\n <li>\n Severe COVID-19: COVID-19 that meets the criteria listed in footnote 2 AND adjudicated by an independent endpoint adjudication committee, in baseline SARS-CoV-2 negative participants.</li>\n <li>\n Solicited and unsolicited AEs collected for a subset of study participants after the initial set of vaccinations. Serious adverse events (SAEs), adverse events of special interest (AESIs), collected for all participants throughout the study.</li>\n</ol>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic1
      • 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_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The site has different sections that will ensure the study is performed as per the protocol and also Good Clinical practice.. Apart from the Principal investigators and co investigaors the different Sections will include 1 receptionist, 1 data manager, 1 data Clerk, 4 nurses, 2 clinical officers, 21Medical officer, 2Harmacist(1 Pharmacist of record and 1 Associate), 2 Quality Managenet officers , 1 records officer and 2 laboratory technicians</p>\n<p>\n The Kisumu CRS has a state of the art laboratory, clinic and pharmacy .</p>\n<p>\n Other supporting sections include the ICT section, transport department as well as the administration department</p>\n
      • other_details_explanation<p>\n This is because the trial is a Covid 19 trial and because this is a pandemic the trial is being conducted in multiple sites in Africa</p>\n
      • other_details_regulatory_notapproved<p>\n KEMRI Scientifics and Ethics Review Unit-27 May 2021</p>\n
      • other_details_regulatory_approved<p>\n None at this point</p>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_duration1 year
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherYes
      • design_controlled_specifyimmediate vs. deferred vaccination with blinded crossover
      • design_controlled_comparatorSodium Chloride 0.9%
      • 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_states7
      • number_of_sites2
      • multi_country_listBotswana, Uganda, Kenya, Malawi, Eswatini, South Africa, Zimbabwe
      • data_monitoring_committeeYes
      • total_enrolment_per_site300
      • total_participants_worldwide14,000
      • 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_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersYes
      • subjects_others_specifyage ≥ 40 and at least one comorbidity known to be associated with severe COVID-19, 2) age ≥ 18 and pregnant, 3) age ≥ 18 and HIV-infected.
      • investigator1_given_namePhilister
      • investigator1_middle_name Adhiambo
      • investigator1_family_nameMadiega
      • investigator1_qualificationResearcher
      • investigator1_professional_addressPO BOX 1578 Kisumu
      • investigator1_telephone0703704299
      • investigator1_emailPadhiambo@kemricdc.org
      • organisations_transferred_No
      • number_participants500
      • notification
      • approval_date05-08-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted05-08-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe application has been approved by the experts
      • final_report
      • implication_results
      • quantity_imported
      • quantity_dispensed
      • quantity_destroyed
      • quantity_exported
      • balance_site
      • final_date0000-00-00
      • modified2025-08-12 15:10:05
      • created2021-05-22 16:22:47
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id655
        • application_id1007
        • given_nameGrace
        • middle_nameMboya
        • family_nameMugure
        • qualificationMedical Officer
        • professional_addressPO BOX 1578 Kisumu
        • telephone0705300452
        • emailGmboya@kemricdc.org
        • created2021-05-24 14:41:49
        • modified2021-08-05 06:28:22
    • SiteDetail(array)
      • 0(array)
        • id904
        • application_id1007
        • county_id42
        • site_nameKEMRI CGHR Kisumu Clinical Research Site
        • physical_addressJaramogi Oginga Odinga Teaching and Referal Hospital
        • contact_detailsPO BOX 1578 Kisumu
        • contact_personDr. Grace Mboya
        • site_capacity(null)
        • misc(null)
        • created2021-05-24 14:41:49
        • modified2021-08-05 06:28:22
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id500
        • application_id1007
        • sponsorSouth African Medical Research Council
        • sponsor_typeOthers
        • contact_person
        • addressFrancie van Zijl Drive Parowvallei, Cape Town; PO Box 19070 7505 Tygerberg, South Africa
        • telephone_number+27 21 938 0911
        • fax_number
        • cell_number+27 21 938 0911
        • email_addressinfo@mrc.ac.za
        • created2021-05-24 14:41:49
        • modified2021-08-05 06:28:22
  • 1(array)
    • Application(array)
      • id830
      • user_id81
      • trial_status_id5
      • abstract_of_study<p>\n Malaria continues to claim the lives of more than 435’000 people each year, largely in Africa¹.  Its elimination is not guaranteed without the development of new control strategies. Ivermectin is a well-known anti-parasitic drug which is being evaluated as a complementary malaria vector control tool. In a previous field randomized controlled trial (RCT) conducted in Burkina Faso (RIMDAMAL), investigating mass drug administration (MDA) of ivermectin (IVM), community members were treated using a single dose of 200mcg/Kg every three weeks for six rounds, leading to a 20% reduction in clinical malaria in children. Despite no indication of increased harm by the repeated 200mcg/kg doses, six rounds of treatment throughout the rainy season may not be easily implementable by control programmes. A dose-finding study conducted in Kenya (IVERMAL) determined the mosquito-killing effect and safety of two alternative dose regimens given on three consecutive days: 300 mcg/kg and 600 mcg/kg. Both three-day regimens resulted in a significant increase in mosquito mortality lasting 21 to 28 days after the last drug intake. The 300mcg/Kg x 3 regimen is not being evaluated for use in MDA programs for malaria control. However, although the dose regimen was found to have a good safety profile, the feasibility of administering three consecutive doses every month and its acceptability by the community may negatively impact adherence to the intervention. The BOHEMIA trial (Broad One-Health Endectocide-based Malaria Intervention in Africa) aims at evaluating MDA of IVM to reduce malaria transmission in Eastern and Southern Africa. The BOHEMIA consortium proposes using three rounds of a single dose of 400mcg/Kg IVM (currently included in the EU label for MDA) based on available pharmacokinetic data and mathematical modelling of plasma levels expected to kill mosquitoes. A direct comparison of this dose regimen and 300mcg/Kg x 3 regimen with entomological and pharmacokinetic outcomes has not yet been done. The current protocol proposes an open-label RCT to support the dose regimen choice of the BOHEMIA trial by comparing the pharmacokinetics (PK) and mosquitocidal effect of single dose 300mcg/Kg IVM on three consecutive days to single dose 400mcg/Kg IVM on one day as well as albendazole as it is being considered as potential comparator. For this purpose, the trial will randomize a total of 30 healthy individuals from Ngerenya to receive one of the four following treatments (2:1:1:1):  1) Single dose oral IVM 400 mcg/Kg (12 participants); 2) Single dose oral IVM 300 mcg/Kg given on three consecutive days (six participants); 3) single dose oral 400mg albendazole (six participants); and 4) no treatment (six participants). Participants will be followed-up up to 28 days, depending on their treatment allocation, during which blood samples will be drawn at regular intervals and its mosquitocidal effect will be assessed. The same blood will be sent to University of Basel in Switzerland for determining the PK of IVM using standard and novel methodologies that will be used during the BOHEMIA field trial.</p>\n
      • study_title<p>\n Mosquitocidal effect and pharmacokinetics of different ivermectin dose regimens in preparation for BOHEMIA cluster randomized controlled trial.</p>\n
      • laymans_summary<address>\n <strong>Lay Title</strong></address>\n<p>\n Evaluation of different deworming drugs to kill mosquitoes.</p>\n<address>\n <strong>    What is the problem/background?</strong></address>\n<p>\n Ivermectin is a drug used for deworming often given to communities to prevent elephantiasis (tende). We also know that mosquitoes die after they bite someone treated with ivermectin. Currently, treating entire communities with ivermectin is being considered as a new way to kill malaria mosquitoes and so reduce malaria. We are not sure what is the best dose of ivermectin that should be used for this purpose. We want to carefully compare two different doses and see which one is better.</p>\n<address>\n <strong>    What questions are we trying to answer?</strong></address>\n<p style=\"margin-left:36.0pt;\">\n a)       How do mosquitoes die if people take ivermectin once (400mcg/Kg) compared to three times (300mcg/kg once a day for 3 days)?</p>\n<p style=\"margin-left:36.0pt;\">\n b)      Is the amount of ivermectin in the blood different, if people take the treatment once, or three times for three days?</p>\n<p style=\"margin-left:36.0pt;\">\n <strong>c)       </strong>Do mosquitoes die if they feed on someone treated with albendazole?</p>\n<address>\n <strong>Where is the study taking place, how many people does it involve and how are they selected?</strong></address>\n<p>\n The study will take place at KEMRI Centre for Geographic Medical Research -Coast (KEMRI CGMR-C) in Kilifi, Kenya. A total of 36 healthy adult (18-45 years old) volunteers from Ngerenya will be asked to participate in the study. Residents of Ngerenya will be told about the project through the community liaison group (CLG) of KEMRI CGMR-C. The study will be presented at baraza community meetings and participants will be invited to participate by community health workers and field workers. During the baraza, the study will be explained. Those interested in participating will provide their contact details o they can be informed when to come to the dispensary for screening. Before screening, all volunteers will be explained the study procedures by an experienced field worker and given an informed consent form and information sheet (ICF) in a language they understand. If a volunteer agrees to participate, clinical staff will do a physical examination and as a few questions to see if they can participate in the study. If the participant is a woman they will be asked about her family planning. A trained nurse will withdraw a small amount of venous blood (9ml - around 2 teaspoons) to check if the person is healthy enough to participate. A malaria test  will also be done. Within a few days the participants will receive their test results.  If anyone is found to have a health problem they will be referred to the closest and most appropriate government health facility.</p>\n<address>\n <strong>    What does the study involve for those who are in it?</strong></address>\n<p>\n We will screen up to 200 volunteers from the Ngerenya community until a total of 36 participants are found. We will recruit 36 participants, of which 6 will be a reserve group and will only be called  to participate if another participant leaves the study.  The other 30 participants will be asked to take one of these treatments orally: 1) ivermectin once; 2) ivermectin three times; 3) albendazole once;  or 4) nothing. Participants will be told which group they are in and given a study calendar with days and times they are to visit KEMRI CGMR-C in Kilifi. Calendars will also be shared with field workers who will remind the participant before each visit. Participants will be asked to come to KEMRI CGMR-C one day before starting the study to check if they are still eligible. If the participant is taking ivermectin they will be asked to stay overnight for two nights during which they will be given a comfortable bed and meals at the Pwani University Resource Centre (PURC) facilities. At PURC, participants will be asked to stay indoors and will be in the presence of a study nurse at all times. Participants will receive their treatment in form of oral tablets, followed by breakfast. Participants who receive ivermectin will be asked to allow the study nurse to insert a cannula in their arm so it is easier to withdraw blood. On this day a nurse will withdraw between 1 and 2 teaspoons of blood every hour (until 10 hours post treatment) from the participants who had received ivermectin. Other participants will only be required to withdraw blood once that day (1 teaspoon) and will not be asked to stay overnight. Depending on the group the participant has been assigned to s/he will be asked to return to KEMRI CGMR-C on the following days post-treatment 1, 2, 3, 4, 7, 10, 14, 21, and 28 days. On each visit the participant will be asked to withdraw 1-2 teaspoons of blood from their vein, those who took ivermectin will also be asked to allow a nurse to prick their finger to obtain 8 drops of blood. The blood taken from the participants will be used for two purposes:  to measure how much ivermectin is in their blood and to feed mosquitoes and see how these die after feeding on the blood. Participants will never be in contact with mosquitoes. The mosquitoes will be fed in the laboratory. During the 28 days after taking the medication, participants will be offered medical care by the study clinician. Participation will be completely voluntary and participants will be allowed to leave the study at any time without having to explain why. If a participant is excluded or chooses to leave, a participant from the reserve group will be replace them. If everyone in the reserve group is called to participate and more participants are needed, the study team will return to Ngerenya and will recruit additional participants to complete the study.</p>\n<address>\n <strong>    What are the benefits and risks/costs of the study for those involved? </strong></address>\n<p>\n Participants will not have any direct benefit from participating in the study. In the long term there may be benefits for the community, as the study will contribute help develop a new way of controlling malaria mosquitoes  that may one day be used in Kenya. However, participants will benefit from being dewormed with ivermectin or albendazole. The control group as well as the participants from the reserve group who were not called to participate, will not be dewormed during the study period; however, they will be offered albendazole at the end of the 28-day follow-up period so they may also have the same benefit. Both ivermectin and albendazole are licensed in Kenya and regularly used. Both medications are usually well tolerated with  rare side-effects. However, there is a risk the drugs may not be well tolerated in participants with certain health problems, for this reason we will check if  participants are healthy enough before recruiting them. Albendazole is licensed in Kenya and causes very few side-effects, however sometimes people may get a skin rash, feel nausea, or have diarrhea. Ivermectin at the dose we want to test (400mcg/Kg) is not approved in Kenya, however this dose is approved in European countries against tende (filariasis). Ivermectin taken on three consecutive days is also not currently licensed in Kenya, however, other studies done in Kenya found this dose to be safe. Ivermectin can sometimes cause temporary side-effects such as blurry vision, tiredness, headache, tremors, dizziness, loss of appetite and stomach discomfort. Those involved in the study may suffer mild discomfort during finger pricks, inserting of the venous cannula and the withdrawing blood as there is a risk of bruising and a slight risk of infection caused by the procedure. Blood withdrawals will not exceed the volumes recommended by the Pharmacy and Poisons Board (PPB) of Kenya. Participants will be compensated for their travel and out-of-pocket expenditure according to existing KEMRI-CGMR-C guidelines.</p>\n<address>\n <strong>    How will the study benefit society?  </strong></address>\n<p>\n The project will benefit society by informing the design of a clinical trial investigating the mass drug administration of ivermectin as new way to control malaria mosquitoes. The development of this intervention may contribute towards malaria elimination.</p>\n<address>\n <strong>    When does the study start and finish?</strong></address>\n<p>\n The study is planned to start once ethical approval is obtained and will be completed within 10 months post approval.</p>\n
      • short_titleBOHEMIA PK400
      • protocol_noECCT/19/12/01
      • version_no1.3
      • date_of_protocol14-10-2019
      • study_drugIvermectin and Albendazole
      • disease_conditionN.A.
      • 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_nameivermectin and albendazole
      • product_type_medical_device_name
      • comparatorYes
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressregulatory@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_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data0
      • 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_applicantMarta Ferreira Maia
      • declaration_date103-12-2019
      • declaration_principal_investigatorMarta Ferreira Maia
      • declaration_date203-12-2019
      • placebo_presentNo
      • study_objectives<h2>\n . Objectives</h2>\n<h3>\n  Primary objective</h3>\n<ol>\n <li>\n Determine cumulative mosquito mortality up to 28 days post blood feeding on volunteers who have been treated with each of the following treatments (at D0+4h, D7, D10, D14, D21, and D28 post treatment):</li>\n</ol>\n<p style=\"margin-left:72.0pt;\">\n A.      Single oral dose of 400 mcg/Kg of ivermectin given once;</p>\n<p style=\"margin-left:72.0pt;\">\n B.      Single oral dose of 300 mcg/Kg of ivermectin given on 3 consecutive days;</p>\n<p style=\"margin-left:72.0pt;\">\n C.      Single oral dose of albendazole 400 mg - proposed comparator for BOHEMIA cRCT;</p>\n<p style=\"margin-left:72.0pt;\">\n D.      No treatment (control).</p>\n<h3>\n  Secondary objective</h3>\n<p>\n Describe the pharmacokinetics of ivermectin during the first 7 days post treatment for each of the following IVM dose regimens: </p>\n<p>\n A. Ivermectin 400 mcg/Kg of ivermectin given once;</p>\n<p>\n B. Ivermectin 300 mcg/Kg of ivermectin given on 3 consecutive days</p>\n
      • principal_inclusion_criteria<ol>\n <li>\n Male or female 18 -45 years old;</li>\n <li>\n Body weight over 50Kg;</li>\n <li>\n Good health or no medical conditions that could interfere with the study according to the opinion of the study clinician;</li>\n <li>\n Willingness to participate voluntarily in all study procedures;</li>\n <li>\n Plans to remain available for study participation within the next 7 months;</li>\n <li>\n Use of effective method of contraception* documented through a family planning card for the duration of study for female participants;</li>\n</ol>\n<p style=\"margin-left:31.5pt;\">\n * Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female subject’s entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository).</p>\n<p>\n vi. Ability to give informed consent and communicate with the study personnel.</p>\n
      • principal_exclusion_criteria<ol>\n <li>\n Feeling sick or presenting signs of sickness, which are considered by the project physician to not be temporary condition or likely to resolve before pre-enrolment screening;</li>\n <li>\n Body weight below 50Kg;</li>\n <li>\n Positive for malaria rapid diagnostic test (mRDT);</li>\n <li>\n Lactating or pregnant verified through ß-hCG urine test;</li>\n <li>\n Clinically significant laboratory abnormality as judged by the study clinician;</li>\n <li>\n Receiving or having received in the past 30 days treatments that could, in the eyes of the investigator, interfere with the study including, but not exclusive to, drugs listed in Tables 1 and 2;</li>\n <li>\n Intake of ivermectin, albendazole, or any other drug or substance that might interfere with the study procedures in the eyes of the study physician;</li>\n <li>\n Hypersensitivity against any of the study drugs or other allergic / hypersensitivity conditions that may, in the eyes of the investigator, interfere with the study.</li>\n</ol>\n
      • primary_end_points<ol>\n <li>\n Mosquito survival up to 28 days post treatment will be assessed by measuring the daily proportion of knocked-down mosquitoes after feeding on blood from participants up to 28 days post treatment with either ivermectin 300mcg/Kg x3, single dose ivermectin 400mcg/Kg x1, single dose albendazole 400mg or no treatment. Cumulative mortality will be estimated by quantifying number of dead mosquitoes in the treatment and control group and then correcting percentage mortality using Abbots formula which corrects for natural causes of mosquito mortality.</li>\n <li>\n The following plasma PK parameters of IVM will be derived either directly from observed data (Cmax, Tmax) or by non-compartmental analysis of the concentration-time profiles):\n <ol style=\"list-style-type:lower-roman;\">\n <li>\n The maximum plasma and capillary blood concentration (Cmax) and time to reach Cmax (Tmax)</li>\n <li>\n The terminal elimination rate constant (Λz) with the respective half-life (t½)</li>\n <li>\n The area under the plasma and capillary blood concentration-time curve from time of last administration to time of last observation (AUCobs).</li>\n </ol>\n </li>\n</ol>\n<p>\n  </p>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • 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_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The trial will be supported by the follwoing staff :</p>\n<p>\n - Two clinicians (Mainga Hamaluba and TBN);</p>\n<p>\n Dr Hamaluba is head of clinical trials at KEMRI Wellcome Trust Research Programme and will appoint a medical officer from her team to work with the project team). Mainga is a qualified clinician. Licence attached.</p>\n<p>\n - Two nurses (TBN - will be hired on LOCUM basis from MoH);</p>\n<p>\n The MoH nurses will be trained and experienced in venopuncture and catheter placement as well as patient monitoring. These will be named by MoH partners from Kilifi District Hospital.</p>\n<p>\n - Two medical entomologists (Marta Maia and Simon Muriu);</p>\n<p>\n Marta Maia has a PhD in medical entomologist with experience in feeding experiments and also evaluation of ivermectin synergists. She is also a trained vector biologist and entomology work package leader of the BOHEMIA consortium. Simon Muriu has a PhD in vector biology and is an experienced researcher from Pwani University, he will provide scientific input on the analysis and reporting of the entomological data.</p>\n<p>\n - One pharmacist (Mwatasa M. Hussein);</p>\n<p>\n Hussein is a trained and registered pharmacist in Kenya. He will provide support from the KEMRI Wellcome Trust phamarcy.</p>\n<p>\n - Two epidemiologists (Carlos Chaccour and Regina Rabinovich);</p>\n<p>\n Regina Rabinovich (MD PhD) is the PI of the BOHEMIA consortium and Carlos Chaccour (MD PhD) is the chief scientific officer and epidemiology work package leader. They are both trained clinicians and experienced in clinical trials.</p>\n<p>\n - One clinical pharmacologist (Felix Hammann);</p>\n<p>\n Felix Hamman is a clinical pharmacologist (MD PhD) with extensive experience collecting and analysing PK data.</p>\n<p>\n - One analytical pharmacologist (Urs Duthaler);</p>\n<p>\n Urs Duthaler (PhD) is responsible for the analysis of the PK samples using mass spectrometry tools. Urs has a PhD in the respective field and has vast experience on analysing ivermectin PK data from previous trials conducted in Switzerland.</p>\n<p>\n - One insectary technician (Martha Muturi)</p>\n<p>\n Martha Muturi has been working as a insectary technician for over 12 years and has supported several clinical trials that included entomological data outcome measures.</p>\n<p>\n - One PhD student (Jonathan Karisa)</p>\n<p>\n Jonathan is currently registered for PhD under supervision of Dr Marta Maia and Dr Carlos Chaccour. He has experience in entomology data collection as well as various laboratory assays.</p>\n<p>\n KEMRI Wellcome Trust Research Programme has a track record in conducting clinical trials and following GCP standards. The trial is hosted at the CTF (Clinical Trials Facility) and will benefit from the experience and systems already in place KWTRP for conducting clinical trials, including the clinical trials laboratory (CTL), the community liaison group (CLG) and the good relationship with the local community. The site is adjacent to the Kilifi Disitric Hospital where participants can be seen in the unlikely event of an emergency. The hospital is well equipped and has adequate medical staff.</p>\n<p>\n Additional infrastructure in place includes the insectary where disease free mosquitoes are being reared for experimental purposes.</p>\n
      • other_details_explanation<p>\n The study is being conducted in Kenya because the investigational product is a drug that may be used for malaria vector control in Kenya if proven effective during<br />\n the on-going phase III trials in other African countries. It is best to study the pharmacokinetics and pharmacodynamics (mosquitocidal effect) of these endectocidal<br />\n drugs in the target population in order to better understand how these can be used to control malaria vectors.</p>\n
      • other_details_regulatory_notapproved<p>\n No other regulatory authoriy has reviewed this study.</p>\n
      • other_details_regulatory_approved<p>\n No other regulatory authoriy has reviewed this study.</p>\n
      • other_details_regulatory_rejected<p>\n No other regulatory authoriy has reviewed this study. The study has been reviewed by various ethics committees and sucessfully obtained approvals. These include the World Health Organization Ethics Review Committee (WHO ERC), the scientific and ethics review unit of KEMRI (SERU), Oxford Tropical Research Ethics Committee (OxREC) and University of Barcelona IRB.</p>\n
      • other_details_regulatory_halted<p>\n Not applicable.</p>\n
      • estimated_durationEstimated 10 months after obtaining regulatory approval.
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorNo treatment
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKilifi
      • single_site_physical_addressKEMRI Wellcome Trust Research Programme, Off Hospital Road
      • single_site_contact_personMarta Ferreira Maia
      • single_site_telephone+265791639964
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteTotal of 36 healthy participants.
      • total_participants_worldwideTotal of 36 healthy participants.
      • 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_nameMarta
      • investigator1_middle_name
      • investigator1_family_nameFerreira Maia
      • investigator1_qualificationPhD
      • investigator1_professional_addressKEMRI Wellcome Trust, P.O. Box 230-80108, Kilifi
      • investigator1_telephone+254791639964
      • investigator1_emailmmaia@kemri-wellcome.org
      • organisations_transferred_No
      • number_participantsTotal of 36 healthy participants.
      • notification<p>\n None</p>\n
      • approval_date01-04-2020
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted28-03-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonStudy approved
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-03-04 13:16:33
      • created2019-10-17 12:39:11
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id513
        • application_id830
        • given_nameMarta
        • middle_name
        • family_nameFerreira Maia
        • qualificationPhD
        • professional_addressKEMRI Wellcome Trust, P.O. Box 230-80108, Kilifi
        • telephone+254791639964
        • emailmmaia@kemri-wellcome.org
        • created2019-10-17 12:45:11
        • modified2020-03-28 12:15:37
    • SiteDetail(array)
      • 0(array)
        • id672
        • application_id830
        • county_id(null)
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        • site_capacity(null)
        • misc(null)
        • created2019-10-17 12:45:11
        • modified2020-03-28 12:15:37
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id401
        • application_id830
        • sponsorUniversity of Oxford
        • sponsor_typeResearch Institution
        • contact_person
        • addressUniversity of Oxford, Boundary Brook House,( 2nd Floor) Churchill Drive, Headington Oxford OX3 7LQ, United Kingdom
        • telephone_number+44 (0)1865 616537
        • fax_number
        • cell_number+44 (0)1865 616537
        • email_addressgraham.waite@admin.ox.ac.uk
        • created2019-10-17 12:45:11
        • modified2020-03-28 12:15:37
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      • id531
      • user_id32
      • trial_status_id5
      • abstract_of_study<h2>\n <span style=\"font-size: 12px;\">Title: Menstrual cups and cash transfer to reduce sexual and reproductive harm and school dropout in adolescent schoolgirls in western Kenya: a cluster randomised controlled trial.</span></h2>\n<p>\n Short Title: Cups or cash for girls (CCg) trial</p>\n<p>\n Background and rationale: Adolescence is a critical time of psychological and biological change, and advocacy has increased to identify interventions that protect against sexual and reproductive health (SRH) harms, which are disproportionately high among adolescent girls in sub-Saharan Africa. In much of eastern and southern Africa including western Kenya, where unprotected transactional sex is common, young females are highly vulnerable to sexually transmitted infections (STIs), including HIV, and pregnancy resulting in school dropout. While the burden of young female SRH harms is high for individuals, communities and health services, sustainable preventive interventions are lacking. Evidence of a positive association between girls’ education, health and economic potential has strengthened international resolve to improve educational opportunities for adolescent girls. While SRH education has minimal impact on SRH harms, staying in school has shown to protect girls against early marriage, teen pregnancy, and HIV infection, with schoolgirls reporting less frequent sex, and fewer partners with less age disparity. While MDGs focused on primary school attendance, the post-2015 Sustainability Development Goals continue to encourage investment in secondary, tertiary and vocational education to build human capital, innovation and economic growth, but require the support of cost-effective interventions. Interventions using cash transfer (CT) have demonstrated a protective effect on girls SRH (HIV, HSV-2, sexual behaviours, and school indicators)^1-3. Menstrual hygiene management (MHM) is a pervasive problem across low middle income countries (LMICs) and a lack of MHM materials and facilities negatively impact girls’ school-life. This increases girls’ vulnerability to coercive sex, which often creates a pathway to obtain necessities such as soap, sanitary products, and underwear; 10% of 15 year old girls report that they obtain money through sex to purchase sanitary products in western Kenya.⁴To tackle these challenges, our team ran a pilot menstrual study in western Kenya. It provided MHM tools to adolescent girls in the form of reusable menstrual cups and disposable sanitary pads. The results demonstrated a lower prevalence of STI and bacterial vaginosis among girls who were provided with a single menstrual cup (one cup can last up to 10 years), and a lower prevalence of school dropout after 12 months follow-up compared to controls.⁵This pilot requires replication in a larger trial population with longer follow-up. Comparison against CT offers an opportunity to examine the efficacy and cost-effectiveness of these different approaches to improve girls’ life-chances in rural western Kenya. The study is designed to inform evidence-based policy to improve girls’ health, school equity and their life-chances.</p>\n<p>\n Primary objective: To determine the impact of menstrual cups alone, cash transfer alone, or the two in combination, in secondary schoolgirls on a composite of deleterious outcomes (HIV, HSV-2 infection, or school dropout).</p>\n<p>\n Hypothesis: We postulate the interventions tested will break the cycle of sexual and reproductive ill-health, under-achievement, and poverty which impede girls’ successful completion of school.</p>\n<p>\n Overview Study Design: Single site open-label 4-arm, school-cluster randomised controlled superiority trial. Schools are the unit of randomisation (clusters), with girls the unit of measurement. Schools will be randomly allocated into 4 arms using a 1:1:1:1 ratio and permuted block randomisation to minimise bias. Enrollment will be staggered over 2 school terms if logistically required. Girls will be followed-up through graduation and into employment or up to 10 academic terms to determine if they complete secondary school (Form 4). Sealed, opaque envelopes will be prepared with the study allocation. Counsellors conducting HIV and HSV-2 testing, and laboratory technicians will be blinded to the study arm. Field staff who conduct home visits to confirm dropout will also be masked where feasible.</p>\n<p>\n Sites: The study will be conducted in in Siaya County, western Kenya. Dependent on the recruitment rate, enrolment will be expanded to other neighboring counties.</p>\n<p>\n Study Population: Secondary schoolgirls who attend 84 eligible schools in the western Kenya study site. Girls wil be residents of the area, with a history of established menses (>=3 times), no disability preventing participation, with parent or guardian’s consent and girl’s assent. Girls attending bording schools or with visible/declared pregnancy will be excluded at baseline.</p>\n<p>\n Study Interventions: 1. One menstrual cup (Mooncup®) with handwash soap termly; 2. Cash transfer (CT; girls’ pocket money) via local community/mobile banking with financial literacy; 3. A combination of cup and CT interventions; 4. ‘Usual practice’ (control) with handwash soap termly.</p>\n<p>\n Outcome Measures: Primary efficacy outcome: Composite endpoint comprised of incident HIV, HSV-2, and all-cause school dropout, by end of study. Key secondary outcomes include incident HIV, HSV-2, school dropout, BV and reported sexual behaviours including pregnancy, quality of life measures, school indicators (performance, grade repitition, re-enrolment, absence), and cost-effectiveness. Primary safety outcome measure: toxic shock syndrome (TSS), and severe violence associated with intervention. Key secondary safety outcome include contamination on menstrual cups and other emergent harms associated with the interventions.</p>\n<p>\n Follow-up procedures: HIV and HSV-2 serostatus will be assessed at baseline and around the time of final school term (Form 4), with interim testing or annual testing if funding allows, including for bacterial vaginosis and other STI. School dropout will be assessed every term until the end of Form (class) 4. Other endpoints will be evaluated at baseline and following completion of behavioural surveys each intervention year. Safety monitoring of TSS and physical violence will be conducted throughout by study nurses, supplemented by health facility registry reviews and evaluation of HDSS census mortality data.</p>\n<p>\n Sample size: Main trial: 3864 participants (in 4 arms; 966 per arm), in 84 clusters (21 schools per arm).</p>\n<p>\n Data Analysis: Primary trial analyses will be based on the intention to treat principle and a secondary analyses will also be done on the per protocol population. Generalised estimating equation (GEE) log binomial models will be used to analyse the primary endpoint and its components. The GEE model will include the arm as a fixed effect and school as a cluster effect. The RR values for the 5 pre-specified primary comparisons together with their 95% confidence intervals will be derived from the GEE model. The secondary endpoints will be analysed similarly using GEE models. For GEE analysis of a continuous endpoint such as quality of life, normal distribution and identity link functions will be used. For GEE analysis of a binary outcome (such as having an event of STI, HIV, pregnancy, or school dropout), binomial distribution and log link functions will be used; for GEE analysis of recurrence of events (such as number of sexual partners during a specific time), Poisson distribution and log link functions will be used. Covariate adjusted analysis of primary endpoint will be performed within the GEE framework with treatment as the study variable, and other predictors as covariates, and school as cluster effect. For qualitative analysis, FGD recordings will be transcribed verbatim with back translation. Transcripts will analysed using thematic analysis by study group, 2 researchers will separately assign codes for emergent themes, subthemes patterns, and associations using NVIVO with intercoder reliability checked and consensus reached following discussion. As themes emerge, differences and similarities will be compared across trial arms, and between study groups. Qualitative data from in depth interviews will be similarly evaluated.</p>\n<p>\n Partner institutions: KEMRI and CDC Collaboration, Kisumu, western Kenya; Kenya Ministries of Education and Health, Liverpool School of Tropical Medicine; US Centers for Disease Control and Prevention; Safe Water and AIDS Project.</p>\n<p>\n Funding: Joint Global Health Trials (Department for International Development, Medical Research Council, Wellcome Trust), UK.</p>\n
      • study_title<p>\n Menstrual cups and cash transfer to reduce sexual and reproductive harm and school dropout in adolescent schoolgirls in western Kenya: a cluster randomised controlled trial</p>\n
      • laymans_summary<p>\n Adolescent girls in impoverished settings suffer from inadequate menstrual hygiene to manage their periods. Lack of materials result in girls’ poor engagement with schooling, or miss schooling due to stigma and shame, and can lead to an increase in reproductive tract infections due to poor hygiene. As a consequence, girls may seek to acquire menstrual products from boys and men, placing them at increased risk of sexual infections such as HIV or HSV-2, or pregnancy, which in turn will lead to girls dropping out of school.</p>\n<p>\n  </p>\n<p>\n <strong>We conducted a study among 4137 adolescent girls attending 96 secondary schools in Siaya County, rural western Kenya. We provided a menstrual product (a menstrual cup), or pocket money, or both to girls (allocated by school), and compared their ‘outcomes’ with girls not provided an intervention until the end of the project (these girls then received a menstrual cup). Our results indicate that the menstrual cup was effective in supporting girls’ menstrual hygiene at school without any serious adverse outcomes. We found girls who used cups had lower rates of HSV-2 infection, and school dropout, and a reduction in the rate of pregnancy while in school. Girls receiving the cup and pocket money also had a reduction in dropout but pocket money alone did not improve girls’ health or schooling outcomes. No serious adverse effects occurred with provision of the cup or pocket money to girls. These findings suggest a menstrual product like a menstrual cup can greatly improve schoolgirls sexual and reproductive health and help them complete their secondary school education.</strong></p>\n
      • short_titleCups or Cash for Girls Trial
      • protocol_noECCT/16/07/06
      • version_nov1.2-14 April 2016
      • date_of_protocol14-04-2016
      • study_drugMenstrual cup v cash transfer
      • disease_conditionSexual and reproductive health
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_nameMenstrual cup (Mooncup®)
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresstsang@kemricdc.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_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data0
      • 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 Daniel Kwaro, local PI
      • declaration_date125-07-2016
      • declaration_principal_investigatorDr Penelope Phillips-Howard PI, Liverpool School of Tropical Medicine
      • declaration_date225-07-2016
      • placebo_presentNo
      • study_objectives<div>\n AIM AND OBJECTIVES</div>\n<ul>\n <li>\n The overall aim is to inform evidence-based policy to develop intervention programmes which improve adolescent girls’ health, school equity and life-chances.</li>\n</ul>\n<div>\n PRIMARY OBJECTIVE</div>\n<ul>\n <li>\n To determine the impact of menstrual cups or cash transfer alone, or in combination, provided to secondary schoolgirls, on a composite of deleterious outcomes (HIV, HSV-2 infection, and school dropout).</li>\n</ul>\n<div>\n SECONDARY OBJECTIVES</div>\n<ol>\n <li>\n To measure the age-specific differences in the acquisition of HIV and HSV-2 infections in secondary schoolgirls and risk factors for incident HIV and HSV-2 infections.</li>\n <li>\n To determine the risk, risk factors and reasons for dropout and other school indicators among secondary schoolgirls examining the influence of social, epidemiological, and/or health characteristics.</li>\n <li>\n To determine the cost benefit of menstrual cup and CT programmes for schoolgirls by assessing the cost savings of outcomes averted, for individual and combined interventions, and resulting societal impact.</li>\n <li>\n To determine the safety of menstrual cups use, including risk of cup contamination over time, serious adverse events, and identify factors that increase or modify this risk.</li>\n <li>\n To determine factors affecting how adolescent girls spend CT money, and what training is required to support their financial literacy and decision-making.</li>\n <li>\n To determine any adverse outcomes associated with CT and evaluate ways to mitigate risk.</li>\n <li>\n To determine the impact of the interventions on girls' sexual behaviours, including age of sexual début, coerced sex, number of partners, age of partners, pregnancy, condom use and use of contraception.</li>\n <li>\n To examine programme implementation for interventions in schools, working with beneficiaries and stakeholders to develop programme implementation packages.</li>\n <li>\n If funding is available, examine the effect of interventions on other sexually transmitted infections and bacterial vaginosis.</li>\n</ol>\n
      • principal_inclusion_criteria<div>\n Inclusion criteria for schools</div>\n<ul>\n <li>\n • Secondary school in study area</li>\n <li>\n • Girls or co-educational school</li>\n <li>\n • Day school</li>\n <li>\n • Approval by Head Teacher in consultation with teachers, parents, and students</li>\n</ul>\n<div>\n Inclusion criteria for participants</div>\n<ul>\n <li>\n Attend secondary day schools in the study area at enrolment</li>\n <li>\n Resident of the study area</li>\n <li>\n Have a history of established menses (>=3 times)</li>\n <li>\n Have no disability preventing participation i.e. school for the blind</li>\n <li>\n Have received parent or guardian’s consent and assent to participation.</li>\n</ul>\n<div>\n  </div>\n
      • principal_exclusion_criteria<div>\n <div>\n Exclusion criteria for schools</div>\n <ul>\n <li>\n Boys only school</li>\n <li>\n Boarding schools</li>\n <li>\n Special needs schools (i.e. for the blind)</li>\n </ul>\n</div>\n<div>\n Exclusion criteria for participants</div>\n<ul>\n <li>\n Attend boarding schools</li>\n <li>\n Pregnant at time of enrolment (declared or confirmed)</li>\n <li>\n Parental or own refusal</li>\n</ul>\n
      • primary_end_points<p>\n Composite endpoint comprised of incident HIV, HSV-2, and all-cause school dropout, by end of study.�</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyTo examine if provision of a menstrual product, or pocket money reduces girls need to engage in transactional sex to obtain sanitary hygiene or other essential items, thus reducing school dropout or sexual risks, compared with girls under usual practice.
      • 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<p>\n � Principal Investigators - adolescent sexual health and menstruation - Dr Penelope Phillips-Howard; clinician and HIV/HSV-2 specialist Dr� Daniel Kwaro (both � � � � have been PI on numerous studies).</p>\n<p>\n � � Study Coordinator,� Elizabeth Nyothach,� programme management experience, ran pilot study</p>\n<p>\n � � Data Manager and supervising head of demographic surveillance</p>\n<p>\n � � Trial Statistician and 1 senior data manager providing trial statistical support and oversight</p>\n<p>\n � � Pharmaco-vigilance supervision, expert in adverse event monitoring ; and Annemeike van Eijk clinician</p>\n<p>\n � � Full time on-site study nurses, experts in adolescent sexual and reproductive health, girls menstruation and menstrual cup use</p>\n<p>\n � � Laboratory technologists at KEMRI</p>\n<p>\n � � HIV testing and counselling survey staff , experts in HIV TC including in adolescents</p>\n<p>\n � � Community interviewers, experts in field surveys</p>\n<p>\n � � Qualitative field workers, experts in focus group discussions</p>\n<p>\n � � Implementation experts to provide training on use of interventions to girls in school</p>\n<p>\n � � Field survey staff experienced in Water and Sanitation assessments for schools</p>\n<p>\n � � Other support (academic) - health economics, clinical epidemiologists, HIV, HSV2, laboratory experts.</p>\n<p style=\"margin-left:18.0pt;\">\n Other support (local experts and field) � - local community health workers; and linkage with health facilities; ministry of health and education�</p>\n
      • other_details_explanation<p style=\"margin-left:27.75pt;\">\n Schoolgirls in rural Siaya County have no access to menstruation, this places them at risk of seeking money through transactional sex to obtain sanitary products; by providing menstrual cups (or cash) the trial hypothesises this reduces their risk of sexual exposure; thus reduces their risk of sexual and reproductive harms (such as HIV, and HSV-2 sexually transmitted infections), and drop out from school.�</p>\n
      • other_details_regulatory_notapproved<p>\n Liverpool School of Tropical Medicine (LSTM) IRB (13 July 2016)</p>\n
      • other_details_regulatory_approved<div>\n �</div>\n<div>\n <span style=\"font-family: Arial, sans-serif; font-size: 16px; line-height: 18.4px; text-indent: -24px;\">Kenya Medical Research Institute (KEMRI)-SERU-12-May-2016</span></div>\n<div>\n �</div>\n<div>\n <span style=\"font-family: Arial, sans-serif; font-size: 16px; line-height: 18.4px;\">Centers for Disease Control and Prevention USA (CDC) IRB -31-May-2016</span></div>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration3.3 years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorgirls using their usual p
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaSiaya County
      • single_site_physical_addressKenya Medical Research Institute, PO Box 1578
      • single_site_contact_personDr Daniel Kwaro
      • single_site_telephone0700 858 288
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site3864
      • total_participants_worldwide3864
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifythe subjects who are under 18 years (minors) will give assent after their parents have given consent
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_namePenelope
      • investigator1_middle_nameAnne
      • investigator1_family_namePhillips-Howard
      • investigator1_qualificationPhD
      • investigator1_professional_addressDepartment of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA, Liverpool, UK, and Kenya Medical Research Institute (KEMRI) Centre for Global Health Research, P.O.Box 1578, 40100 Kisumu
      • investigator1_telephonemobile 0702 126 188; UK mobile +44 798 543 1005
      • investigator1_emailPenelope.Phillips-Howard@lstmed.ac.uk
      • organisations_transferred_Yes
      • number_participants3864
      • notification<p>\n Menstrual cups are available throughout the world, with at least 25 brands used by many millions of girls and women, including in the USA, Europe, countries of sub-Saharan Africa, India, and south America.  The brand we have chosen, Moocups, has FDA approval, is made to ISO international standards and is marketed internationally.  It is currently sold wholesale in 55 countries throughout the world - Argentina, Austria, Belgium, Brazil, Chile, Croatia, Czech Republic, Denmark, Ecuador, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Indonesia, Ireland,  Israel, Italy, Kenya, Luxembourg, Malaysia, Mongolia, Namibia, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Portugal, Réunion, France, Romania, Russia, Singapore, Slovenia, South Africa, South Korea, Spain, Switzerland, UK, Ukraine, Uruguay, Vietnam.</p>\n
      • approval_date19-10-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted17-03-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:642px;\" width=\"642\">\n <tbody>\n <tr>\n <td style=\"width:151px;height:36px;\">\n <p style=\"margin-left:8.45pt;\">\n Full title of study</p>\n </td>\n <td colspan=\"3\" style=\"width:491px;height:36px;\">\n <p style=\"margin-left:8.75pt;\">\n Menstrual cups and cash transfer to reduce sexual and reproductive harm and school dropout in adolescent schoolgirls in western Kenya: a cluster randomised controlled trial</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:151px;height:51px;\">\n <p style=\"margin-left:8.45pt;\">\n Start date</p>\n </td>\n <td style=\"width:208px;height:51px;\">\n <p>\n Start enrolment 28 Feb 2017</p>\n <p>\n Enrolment closed 6 July 2018</p>\n </td>\n <td style=\"width:85px;height:51px;\">\n <p align=\"center\" style=\"margin-left:-6.75pt;\">\n End date</p>\n </td>\n <td style=\"width:198px;height:51px;\">\n <p>\n Last follow-up 30 June 2021</p>\n <p>\n Data locked 20 May 2022</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:151px;height:27px;\">\n <p style=\"margin-left:8.45pt;\">\n Sponsor</p>\n </td>\n <td colspan=\"3\" style=\"width:491px;height:27px;\">\n <p>\n Liverpool School of Tropical Medicine</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:151px;height:27px;\">\n <p style=\"margin-left:8.45pt;\">\n Funder</p>\n </td>\n <td colspan=\"3\" style=\"width:491px;height:27px;\">\n <p>\n MRC/DfID/Wellcome Trust; Joint Global Health Trials (MR/N006046/1)</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:151px;height:18px;\">\n <p style=\"margin-left:8.45pt;\">\n Trial registration no.</p>\n </td>\n <td colspan=\"3\" style=\"width:491px;height:18px;\">\n <p>\n NCT03051789 (Clinical Trials); PACTR202003815291283 (Pan African Registry)</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:642px;height:36px;\">\n <p>\n Few rigorous studies have measured menstrual interventions effect on adolescent girls’ sexual and reproductive harms and schooling. We conducted a 4-arm cluster randomised controlled trial in western Kenya to test if menstrual cups or conditional cash transfers (CT) can reduce the incidence of HIV, HSV-2, and school dropout as a composite primary outcome in secondary schoolgirls. Girls attending a participating school, in an eligible class year, had reached menarche, were not visibly pregnant, resided in the study area and had no disability precluding participation were invited.</p>\n <p>\n  </p>\n <p>\n We enrolled 4137 girls in 96 secondary day schools after parental consent and girls’ assent. Based on randomisation of schools, girls received either one menstrual cup, CT, both CT and a cup, or were controls. All girls received puberty and hygiene training, and interventions were combined with use and safety training. Sociodemographic and behavioural surveys and biomarker data were collected at baseline, midway and at end of study to measure HIV, HSV-2, and associated risk factors. School attendance was monitored via school registers and home visits confirmed if girls dropped out or transferred schools. Adverse event monitoring was conducted throughout the trial. Data were analysed using multi-level generalized linear models and  controlled for baseline covariates. Trial registration: ClinicalTrials.gov NCT03051789.</p>\n <p>\n  </p>\n <p>\n Of 4137 girls enrolled, 4106 completed follow up between 2017 and June 2021. No significant differences were seen in the primary composite outcome between intervention groups and control in the intention-to-treat population, but menstrual cups were protective against HSV-2. In the per protocol population, cups reduced the incidence of the primary composite outcome,  decreased school dropout and pregnancy. Girls using the combined intervention had a decreased risk of school dropout relative to controls. No serious adverse events were associated with either intervention. We conclude that menstrual cups provide schoolgirls protection against school dropout, HSV-2, and pregnancy, and are a valuable intervention for improving girls’ SRH and schooling.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • implication_results<p>\n <span lang=\"EN-GB\" style=\"font-size: 11pt; font-family: Calibri, sans-serif;\">This trial adds to a limited body of evidence on the effect of menstrual cups and/or conditional cash transfer on girls’ SRH and schooling. Menstrual cups were found to be protective against HSV-2, school dropout, and adolescent pregnancy with no evidence of serious adverse events. These results confirm that menstrual cups can be used by schoolgirls, safely and effectively, and can be considered by policy makers and programmes as a solution to improve girls’ menstrual needs, while helping to reduce sexual and reproductive harms, and improve girls’ chances of completing their schooling. </span></p>\n
      • quantity_imported2873
      • quantity_dispensed2605
      • quantity_destroyed0
      • quantity_exported0
      • balance_site268
      • final_date0000-00-00
      • modified2023-06-09 12:09:28
      • created2016-07-20 15:22:40
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id345
        • application_id531
        • given_namePenelope
        • middle_nameAnne
        • family_namePhillips-Howard
        • qualificationPhD
        • professional_addressDepartment of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA, Liverpool, UK, and Kenya Medical Research Institute (KEMRI) Centre for Global Health Research, P.O.Box 1578, 40100 Kisumu,
        • telephonemobile 0702 126 188; UK mobile +44 798 543 1005
        • emailPenelope.Phillips-Howard@lstmed.ac.uk
        • created2016-07-20 15:24:02
        • modified2020-03-17 14:53:37
      • 1(array)
        • id346
        • application_id531
        • given_nameDaniel
        • middle_nameOluoch
        • family_nameKwaro
        • qualificationMD
        • professional_addressKenya Medical Research Institute (KEMRI) Centre for Global Health Research, P.O.Box 1578, 40100 Kisumu, Kenya
        • telephonemobile: 0700 858 288
        • emailDKwaro@kemricdc.org
        • created2016-07-25 10:19:50
        • modified2020-03-17 14:53:37
    • SiteDetail(array)
      • 0(array)
        • id413
        • application_id531
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2016-07-20 15:24:02
        • modified2020-03-17 14:53:37
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id276
        • application_id531
        • sponsorLiverpool School of Tropical Medicine
        • sponsor_typeResearch Institution
        • contact_personCarl Henry
        • addressTrial governance, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK
        • telephone_number+44 (0) 151 705 3794
        • fax_number
        • cell_number+44 (0) 7701050237
        • email_addressCarl.Henry@lstmed.ac.uk
        • created2016-07-20 15:24:02
        • modified2020-03-17 14:53:37
  • 3(array)
    • Application(array)
      • id314
      • user_id77
      • trial_status_id5
      • abstract_of_study<div>\n <strong>DESIGN</strong> A5288 is an open-label phase IV, prospective interventional, strategy study in resource-limited settings (RLS) for HIV-infected participants with triple-class experience or resistance to [nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), and protease inhibitors (PIs)] and who are failing their current regimen. The use of novel agents and contemporary management tools that include standard genotyping, plasma viral load (VL) monitoring will be evaluated. The screening genotype results and antiretroviral (ARV) history will be used to allocate potential participants to one of the four cohorts and for selection of ARV regimen for each potential participant. Refer to the flow chart,</div>\n<div>\n  </div>\n<div>\n At sites where feasible and relevant, the study will also conduct an adherence study. This will be a randomized comparison of cell phone-based adherence intervention plus local standard-of-care adherence procedures (CPI+SOC) versus the SOC adherence procedures.</div>\n<div>\n  </div>\n<div>\n <strong>Genotyping and Identification of Cohort and ARV Regimen</strong></div>\n<div>\n A standard viral population-based genotype assay determining resistance in protease and partial reverse transcriptase (RT) will be performed in real time at screening. Following receipt of the genotype resistance report, the site investigator will make the initial recommendation for each potential participant (ie, candidate) with regard to the following:</div>\n<div>\n 1) Selection of the appropriate cohort</div>\n<div>\n       AND</div>\n<div>\n 2) Planned ARV regimen if the potential participant will be placed in Cohort A (switch of NRTIs to study-provided NRTIs is allowed but not required)</div>\n<div>\n       OR</div>\n<div>\n Choice of at least two NRTIs if the potential participant is to be placed into Cohort B or Cohort C</div>\n<div>\n       OR</div>\n<div>\n <div>\n The proposed ARV regimen if the potential participant is to be placed into Cohort D.</div>\n <div>\n  </div>\n <div>\n The Clinical Management Committee (CMC) of the A5288 protocol team will review and confirm the site’s recommendation via the CoSPAR System (ACS). After CMC approval of the site-selected cohort and site-recommended regimen options, candidates will be assigned to one of the cohorts, as outlined above.</div>\n <div>\n  </div>\n <div>\n In the event of a confirmed VF on study, participants agreeing to continue in the study will have another genotype resistance test and will be assigned to a Step 2 cohort/ARV treatment group following receipt of the genotype resistance report. The Step 2 cohort selection and confirmation process will be the same as for Step 1 except that for the Step 2 cohort and regimen selection, both genotype resistance reports from screening and Step 1 will be considered. At the completion of Steps 1 and 2 (see Duration below), participants taking RAL, DRV, or ETR may remain on study by entering Step 3. In Step 3, RAL, DRV, and ETR will be provided through the study for up to 96 additional weeks. Participants will have twice yearly clinic visits and sites will be asked to provide information about the local standard of care follow-up that is being provided outside of the study.</div>\n <div>\n  </div>\n <div>\n <strong>DURATION </strong>48 weeks after registration/randomization of the last participant (Steps 1 and 2); study completion is defined as remaining in study follow up for this period of time. Step 3, an optional step for participants taking RAL, DRV, or ETR at the study completion, is an additional 96 weeks beginning at study completion.</div>\n <div>\n  </div>\n <div>\n <strong>SAMPLE SIZE</strong> 500 participants.</div>\n <div>\n  </div>\n <div>\n <strong>POPULATION</strong> HIV-1-infected males and females at non-US sites, aged ≥18 years, who have experience with or resistance to NRTIs, NNRTIs, and PIs, and are currently failing a PI-containing regimen. </div>\n <div>\n  </div>\n <div>\n <strong>RANDOMIZATION </strong>Following cohort registration (Cohort A, sub-cohort B3, or Cohorts C or and D) or randomization (to sub-cohorts B1 or B2; see below), participants at sites that are participating in the adherence study will be randomized 1:1 to either CPI+SOC or to SOC adherence procedures.</div>\n <div>\n Candidates assigned to Cohort B will be randomized 1:1 at study entry to sub-cohort B1 or B2 if they do not have active hepatitis B infection. Candidates assigned to Cohort B who have active hepatitis B infection will be placed into sub-cohort B3 at study entry. Active hepatitis B infection is defined as HBsAg+ at screening or having a history of HBsAg+ in the past with no subsequent documented positive anti-HBsAb and currently on therapy with drugs active against hepatitis B.</div>\n <div>\n  </div>\n <div>\n <strong>REGIMEN</strong> Cohort Profiles and Proposed ARV Regimens (Steps 1 and 2)</div>\n <div>\n Cohort A: No resistance to NRTIs, PIs, or NNRTI Continue current second-line regimen; NRTIs can be modified</div>\n <div>\n Cohort B: Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs)</div>\n <div>\n Participants without active hepatitis B infection at screening will be randomized 1:1 to sub-cohort B1 or B2 Sub-cohort B1: Best available NRTIs, RAL, and DRV/RTV Sub-cohort B2: ETR, RAL, and DRV/RTV</div>\n <div>\n Participants with active hepatitis B infection at screening will be assigned to: Sub-cohort B3: RAL, DRV/RTV, and FTC/TDF or TDF plus 3TC</div>\n <div>\n Cohort C: Resistance to NRTIs and ETR or resistance to ETR alone (and may have resistance to PIs other than DRV) Best available NRTIs, RAL, and DRV/RTV</div>\n <div>\n Cohort D: Multiple NRTI resistance and/or DRV/RTV resistance or prior RAL exposure Best available regimen, including study-provided and any locally available drugs</div>\n <div>\n  </div>\n <div>\n DRV, ETR, RAL, FTC/TDF, and RTV will be provided by the study for use in study regimens. All other study-required regimen drugs must be obtained locally by the participants from their providers before registration/randomization. Support for the provision of rifabutin (RBT) will be provided through the study.</div>\n <div>\n  </div>\n <div>\n <div>\n <strong>Screening Procedures for Cohort Identification and ARV Regimen Selection</strong></div>\n <div>\n Confirmation of Virologic Failure Viral load/s performed (need two HIV-1 RNA results that are ≥1000 copies/mL) Sample collected for Real-Time Genotype assay (protease and partial RT). Resistance Testing and Cohort Identification Screening genotype sample shipped to regional testing laboratory Resistance results sent back to site in real time Based on genotyping results and ARV history, site identifies appropriate cohort, NRTI options (for Cohorts A, B, and C), and proposed ARV regimen for Cohort D Site completes and enters data in the Cohort Selection/Proposed ARV Regimen (CoSPAR) and the Screening HIV-1 RNA and Genotype Tracking forms, uses file exchange utility to attach the genotype resistance report to the A5288 CoSpar System (ACS) and enters the screening tracking form The ACS sends notification via email to CMC that these are ready for review CMC reviews/confirms site selection of cohort and ARV regimen; sends communication to site using the ACS</div>\n <div>\n Cohort A</div>\n <div>\n         Continue 2nd line regimen; NRTIs can be modified</div>\n <div>\n         Randomized 1:1 to CPI+SOC or SOC</div>\n <div>\n Cohort B</div>\n <div>\n         Randomized 1:1 to sub-cohort B1 or B2 or assigned to B3</div>\n <div>\n Cohort C</div>\n <div>\n         Best available NRTIs, RAL and DRV/RTV</div>\n <div>\n         Randomized 1:1 to CPI+SOC or SOC</div>\n <div>\n Cohort D</div>\n <div>\n         Best available regimen, includes study-provided and any locally available drugs</div>\n <div>\n         Randomized 1:1 to CPI+SOC or SOC</div>\n <div>\n Sub-cohort B1</div>\n <div>\n         Best available NRTIs, RAL and DRV/RTV</div>\n <div>\n         Randomized 1:1 to CPI+SOC or SOC</div>\n <div>\n Sub-cohort B2</div>\n <div>\n         ETR, RAL, and DRV/RTV</div>\n <div>\n         Randomized 1:1 to CPI+SOC or SOC</div>\n <div>\n  </div>\n <div>\n 1st Confirmed On-Study Virologic Failure (VF)</div>\n <div>\n Ship samples for real-time genotyping (protease, partial RT, and integrase [for participants on a RAL-containing regimen]) as soon as VF is confirmed.</div>\n <div>\n  </div>\n <div>\n Step 2</div>\n <div>\n Participants may change their ARV regimen (with CMC approval) after consideration of the screening and Step 1 VF genotype resistance reports and will remain on-study on Step 2 (and, as applicable, in the same randomized adherence study arm) through study completion. If there is second or subsequent confirmed VF on study, samples will be sent for batched genotyping.</div>\n <div>\n  </div>\n <div>\n Step 1 Entry</div>\n <div>\n Allocation to Cohort and Initiation of Study Regimen (randomization to adherence study conducted only at sites participating in the adherence study)</div>\n <div>\n Sub-cohort B3</div>\n <div>\n RAL, DRV/RTV, and FTC/TDF or TDF plus 3TC</div>\n <div>\n Randomized 1:1 to CPI+SOC or SOC</div>\n <div>\n  </div>\n <div>\n Step 3 (Optional)</div>\n <div>\n At the end of Step 1 and Step 2 follow-up, participants taking RAL, ETR, or DRV may enter Step 3 and continue to receive these drugs through the study for up to 96 additional weeks.</div>\n </div>\n</div>\n<div>\n  </div>\n<div>\n <strong>Hypotheses</strong></div>\n<div>\n The availability of novel antiretroviral (ARV) agents and use of contemporary management tools for selection and monitoring of third-line treatment will enable a ≥ 65% rate of successful virologic control at 48 weeks of follow-up.</div>\n<div>\n  </div>\n<div>\n <strong>Primary Objective</strong></div>\n<div>\n To use novel agents and contemporary management tools, including standard genotyping to select an appropriate third-line regimen, interventions to improve adherence and plasma viral load (VL) monitoring, in order to achieve a ≥ 65% rate of virologic control at 48 weeks of follow-up.</div>\n<div>\n  </div>\n<div>\n <strong>Secondary Objectives</strong></div>\n<ol>\n <li>\n To characterize changes in HIV-1 RNA and CD4+ T-cell counts over 48 weeks and durability of responses after 48 weeks, as well as clinical outcomes (AIDS-defining and non-AIDS-defining events, hospitalizations and deaths) in four treatment groups (Cohorts A-D).</li>\n <li>\n To characterize the tolerability of the regimens in four treatment groups (Cohorts A-D).</li>\n <li>\n To characterize changes in metabolic outcomes including fasting lipids at 48 weeks among the regimens in four treatment groups (Cohorts A-D).</li>\n <li>\n To assess the effect of a CPI+SOC compared to SOC adherence procedures on the rate of virologic control at 48 weeks of follow-up.</li>\n <li>\n To determine the safety of combinations of third-line ARV therapy in terms of rates of treatment modification or discontinuation for the treatment of HIV-1 infection and to characterize drug-associated toxicities.</li>\n <li>\n To compare changes in HIV-1 RNA and CD4+ T-cell counts over 48 weeks, durability of responses after 48 weeks, and clinical outcomes (AIDS-defining and non-AIDS-defining events and deaths) of CPI+SOC versus SOC adherence procedures.</li>\n <li>\n To compare the tolerability of third-line regimens among participants receiving CPI+SOC versus SOC adherence procedures.</li>\n <li>\n In Cohort B, among participants without active hepatitis B infection, to explore whether the combination of ETR+DRV/RTV+RAL (etravirine, ritonavir-boosted darunavir, raltegravir) is associated with better virologic control, CD4+ T-cell responses, and tolerability than best available NRTIs+DRV/RTV+RAL.</li>\n</ol>\n<div>\n <ol>\n <li>\n To determine the prevalence at enrollment of resistance mutations detected on a population-based and minority-variant level in the four treatment groups (Cohorts A-D), and to explore prevalence by viral subtype.</li>\n <li>\n To describe the mutation patterns and accumulation of mutations over time in the participants experiencing viral failure.</li>\n <li>\n To evaluate the impact of predictors, including viral subtype, baseline mutations and polymorphisms occurring in gag, protease, reverse transcriptase, and integrase (IN) [detected by population-based genotyping and minority-variant analysis] on the virologic outcomes in the four treatment groups (Cohorts A-D).</li>\n <li>\n To evaluate the association of adherence to the study regimens with virologic outcome.</li>\n <li>\n To provide resource utilization and quality of life (QOL) data to support modeling of cost-effectiveness of ART selected using treatment history and standard genotyping as well as cost-effectiveness of the adherence intervention.</li>\n <li>\n To estimate the incidence of immune reconstitution inflammatory syndrome (IRIS) and describe the clinical presentation and associated pathogens and/or inflammatory conditions.</li>\n <li>\n To describe DRV excretion in breast milk.</li>\n </ol>\n</div>\n<p>\n  </p>\n
      • study_title<p>\n Management Using the Latest Technologies in Resource-limited Settings to Optimize Combination Therapy After Viral Failure (MULTI-OCTAVE)</p>\n
      • laymans_summary<p>\n Title of the study was “Management Using the Latest Technologies in Resource-Limited Settings to Optimize Combination Therapy After Viral Failure (MULTI-OCTAVE).”</p>\n<p>\n The main purpose of this study was to see whether using new anti-HIV drugs along with laboratory and clinical management tools could lead to suppression of HIV at about 1 year in more than 65% of people with HIV presenting with second-line anti-HIV treatment failure. The new anti-HIV drugs were: etravirine (ETR), raltegravir (RAL), and ritonavir-boosted darunavir (DRV). The contemporary management tools included the following:</p>\n<ul>\n <li>\n resistance testing to choose anti-HIV drugs. Resistance tests look at the HIV in your blood to see which drugs might work best to lower your HIV infection</li>\n <li>\n interventions to improve adherence</li>\n <li>\n regular testing of the amount of HIV in your blood.</li>\n</ul>\n<p>\n From Jan 10, 2013, to Sept 10, 2015, 545 people joined this study. The results of the study showed that for people who had resistance to a standard second-line anti-HIV drug (lopinavir, boosted with ritonavir), who took a regimen containing DRV/r and RAL with or without ETR, the study was a success (more than 65% achieved suppression). For people who did not have resistance to lopinavir, who continued to take their second-line anti-HIV drugs; the study was not a success (less than 65% achieved suppression).</p>\n<p>\n We believe that the study results support the use of resistance testing to select appropriate drugs for people with second-line treatment failure. People without resistance to second-line anti-HIV drugs may need additional help and resources to control HIV.</p>\n<p>\n This paper was published in the Lancet journal with the following details;</p>\n<p>\n Beatriz Grinsztejn, Michael D Hughes, Justin Ritz et al. <em>Third-line antiretroviral therapy in low-income and middle-income countries (ACTG A5288): a prospective strategy study. </em>Lancet HIV, July 29, 2019 http://dx.doi.org/10.1016/S2352-3018(19)30146-8</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n
      • short_titleA5288
      • protocol_noECCT/14/08/02
      • version_no1.0
      • date_of_protocol16-09-2011
      • study_drugDurunavir, Emtricitabine, Etravirine, Raltegravir, Rifabutin, Ritonavir
      • disease_conditionHIV
      • 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_nameDarunavir, Emtricitabine, Etravirine, Rlategravir, Rifabutin, Ritonavir
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresseayuo@kemricdc.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_countries1
      • applicant_addendum1
      • 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_applicantAMOS K. O. RAGANG\'
      • declaration_date105-08-2014
      • declaration_principal_investigatorDr. ESTHER MUMBI MAKANGA
      • declaration_date205-08-2014
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<h2>\n Inclusion Criteria for Step 1</h2>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA VL.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n NOTE: The term “licensed” refers to an FDA-approved kit. Non-US sites are encouraged to use FDA-approved methods. If an FDA-approved kit is not available, then sites must use a kit that has been certified or licensed by an oversight body within that country and validated internally.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n WHO and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (eg, indirect versus competitive), or a Western blot or a plasma HIV-1 RNA VL.</p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n Any previous combination of ARV treatment at any time with at least one regimen that contained one NNRTI and two NRTIs which was replaced with a PI-based regimen because of virologic, immunologic, or clinical treatment failure, or because of toxicity.</p>\n<p style=\"margin-left:1.0in;\">\n            </p>\n<p style=\"margin-left:1.0in;\">\n             NOTE: All potential participants with prior RAL exposure will be assigned to Cohort D.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n Current receipt of a PI-based regimen with no regimen change for a minimum of 24 weeks prior to screening.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n NOTE A: Within the 30 days prior to collection of the confirmatory VF sample (see 4.1.4), alteration in dose, dose frequency, or any within-class substitution(s) for intolerance is permitted, as are drug interruptions for fewer than 7 cumulative days.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n NOTE B: There can be no changes and no drug interruptions within the 3 days immediately prior to the collection of the confirmatory VF sample.</p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n Confirmation of VF of current second-line PI-based ART.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n NOTE A: Failure of the current second-line regimen is defined as two consecutive measurements of plasma HIV-1 RNA ≥1000 copies/mL obtained at least 1 day apart while on the current PI-based regimen.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n NOTE B: The first measurement of plasma HIV-1 RNA ≥1000 copies/mL must have been obtained after at least 24 weeks of being on the current PI-based regimen and within 240 days prior to study entry. This measurement may be obtained from any local laboratory or from medical records regardless of the laboratory that performed the test.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n NOTE C: The second measurement of plasma HIV-1 RNA ≥1000 copies/mL must be obtained within 103 days prior to study entry and must be performed in a DAIDS-approved laboratory.</p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n CD4+ T-cell count result from a specimen drawn within 103 days prior to study entry; the date of specimen draw and CD4+ T-cell count must be recorded. </p>\n<p>\n  </p>\n<p style=\"margin-left:.5in;\">\n Laboratory values obtained within 30 days prior to study entry:</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.25in;\">\n ·         Absolute neutrophil count (ANC) ≥ 500/mm³</p>\n<p style=\"margin-left:1.25in;\">\n ·         Hemoglobin ≥ 7.5 g/dL</p>\n<p style=\"margin-left:1.25in;\">\n ·         Platelet count ≥ 40,000/mm³</p>\n<p style=\"margin-left:1.25in;\">\n ·         Creatinine ≤ 2 X upper limit of normal (ULN)</p>\n<p style=\"margin-left:1.25in;\">\n ·         Aspartate aminotransferase (AST), serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT), serum glutamic pyruvic transaminase (SGPT), and alkaline phosphatase ≤ 5 x ULN</p>\n<p style=\"margin-left:1.25in;\">\n ·         Total bilirubin ≤ 2.5 x ULN</p>\n<p style=\"margin-left:1.25in;\">\n NOTE: If the potential participant is taking an indinavir- or atazanavir-containing regimen at the time of screening, total bilirubin ≤ 5 x ULN is acceptable.</p>\n<p style=\"margin-left:1.25in;\">\n ·         Creatinine clearance (CrCl) <u>></u>60 mL/min, either measured or estimated by Cockcroft-Gault equation  </p>\n<p style=\"margin-left:1.25in;\">\n NOTE: A calculator for estimating the CrCl can be found at <u>www.fstrf.org/ACTG/ccc.html</u></p>\n<p style=\"margin-left:1.25in;\">\n ·         Hepatitis B panel that includes HbsAB, HBcAB, and HBsAG or only HBsAG, with plasma stored for later anti-HBs and anti-HBc.</p>\n<p style=\"margin-left:1.25in;\">\n NOTE: Potential participants who are eligible for cohort B and who are positive for active hepatitis B infection will be assigned to sub-cohort B3 at registration/randomization.</p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n Females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, ie, who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, hysterectomy or bilateral salpingectomy or bilateral oophorectomy or tubal ligation) must have a negative serum or urine pregnancy test within 48 hours prior to randomization or registration.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n Female participants of reproductive potential must agree not to participate in the conception process (ie, active attempt to become pregnant, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female participant must use at least one reliable form of contraceptive. Potential female participants must continue to use contraceptives while receiving study treatment and for 6 weeks after stopping study treatment.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.5in;\">\n Acceptable forms of contraceptives include:</p>\n<p style=\"margin-left:1.0in;\">\n ·         Condoms (male or female) with or without a spermicidal agent</p>\n<p style=\"margin-left:1.0in;\">\n ·         Diaphragm or cervical cap with spermicide</p>\n<p style=\"margin-left:2.5in;\">\n ·         Intrauterine device (IUD)</p>\n<p style=\"margin-left:1.0in;\">\n ·         Hormonal contraception</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n Female participants who are not of reproductive potential or whose male partner(s) has documented azoospermia) are not required to use contraceptives. Any statement of self-reported sterility or that of her partner’s must be entered in the source documents. </p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n NOTE: Acceptable documentation of lack of reproductive potential is oral or written documentation from the participant.</p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n Karnofsky performance score ³70 within 30 days prior to study entry.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n Men and women aged ³18 years.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n Ability and willingness of potential participant to provide informed consent.</p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n Willingness of potential participant to adhere to protocol requirements, especially with respect to treatment assignment and ability to obtain non-study provided ART, if needed.</p>\n<p>\n  </p>\n<p>\n Ability to take oral study medications.</p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n No intention of permanent relocation that would preclude attending Step 1 and 2 study follow-up visits.</p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n Availability of a successful, interpretable resistance genotype report from a DAIDS-approved regional genotyping facility from testing performed on a plasma sample that was collected during screening (ie, at or after the date that a sample is collected to confirm HIV-1 virologic failure) and which was shipped to a regional resistance testing laboratory once documentation of two screening plasma HIV-1 RNA values ≥1000 copies/mL was available.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n NOTE:  A repeat test of the original sample is acceptable if the initial genotype results are not available due to technical reasons.   </p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n Identification of a cohort assignment and ARV regimen for use on study, selected from the recommended options provided by the site investigator, and reviewed and approved by the A5288 CMC.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n             NOTE: The final CMC-approved cohort (A, B, C, or D) and planned ARV regimen must be entered into the enrollment system, the ACS, and kept in hardcopy as source documentation at the site. </p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<h2>\n Inclusion Criteria for Step 2</h2>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n Two consecutive measurements of plasma HIV-1 RNA ≥1000 copies/mL obtained at or after 24 weeks on study, at least 24 hours apart, while on Step 1 ARV regimen. Both measurements of plasma HIV-1 RNA ≥1000 copies/mL must be obtained within 120 days prior to Step 2 entry and performed in any DAIDS-approved laboratory.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n NOTE:  Both measurements of plasma HIV-1 RNA must be ≥1000 copies/mL and the results must be available at the site before the plasma sample is shipped for genotyping. The plasma sample for genotyping should be collected and saved on the same day that the second plasma HIV-1 RNA specimen was drawn.</p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n Availability of a successful, interpretable resistance genotype results from a DAIDS-approved regional genotyping facility from testing performed on a plasma sample obtained prior to Step 2 entry and which was shipped to a regional resistance testing laboratory after documentation was received of two consecutive HIV-1 RNA values ≥1000 copies/mL.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n NOTE:  A repeat test of the original sample is acceptable if the initial genotype results are not available due to technical reasons.   </p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n Identification of a Step 2 assignment and ARV regimen for use on study, selected from the recommended options provided by the site investigator, and reviewed and approved by the A5288 CMC.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n NOTE:  The final CMC-approved cohort (A, B, C, or D) and planned ARV regimen for Step 2 must be entered into the enrollment system, the ACS, and kept in hardcopy as source documentation at the site.</p>\n<p>\n  </p>\n<p style=\"margin-left:.5in;\">\n Laboratory values obtained within 56 days prior to Step 2 entry:</p>\n<p>\n  </p>\n<p style=\"margin-left:1.25in;\">\n ·         ANC ≥ 500/mm³</p>\n<p style=\"margin-left:1.25in;\">\n ·         Hemoglobin ≥ 7.5 g/dL</p>\n<p style=\"margin-left:1.25in;\">\n ·         Platelet count ≥ 40,000/mm³</p>\n<p style=\"margin-left:1.25in;\">\n ·         Creatinine ≤ 2 X ULN)</p>\n<p style=\"margin-left:1.25in;\">\n ·         AST, SGOT, ALT, SGPT, and alkaline phosphatase ≤ 5 x ULN</p>\n<p style=\"margin-left:1.25in;\">\n ·         Total bilirubin ≤ 2.5 x ULN</p>\n<p style=\"margin-left:1.25in;\">\n NOTE: If the Step 1 participant is taking an indinavir- or atazanavir-containing regimen at the time of Step 2 screening, total bilirubin ≤ 5 x ULN is acceptable.</p>\n<p style=\"margin-left:1.25in;\">\n ·         Creatinine clearance (CrCl) <u>></u>60 mL/min, either measured or estimated by Cockcroft-Gault equation</p>\n<p style=\"margin-left:1.25in;\">\n NOTE: A calculator for estimating the CrCl can be found at <u>www.fstrf.org/ACTG/ccc.html</u></p>\n<p style=\"margin-left:1.25in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n Willingness of Step 1 participant to adhere to protocol requirements, especially with respect to the Step 2 treatment assignment and ability to obtain non-study provided ART, if needed.</p>\n<p>\n  </p>\n<p>\n Ability to continue to take oral study medications.</p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n No intention of permanent relocation during Step 2 that would preclude attending study follow-up visits.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n Currently taking and agreed to continue the Step 1 ARV study-defined regimen until the Step 2 cohort and Step 2 ARV regimen are approved by the CMC and the drugs are available at the site pharmacy.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<h2>\n Inclusion Criteria for Step 3</h2>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n Current receipt of study-provided RAL, ETR, or DRV.</p>\n
      • principal_exclusion_criteria<h2>\n Exclusion Criteria for Step</h2>\n<h2>\n <span style=\"font-size: 12px;\">Pregnancy or breast-feeding.</span></h2>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.</p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n Concurrent illness or condition that would compromise the ability to take study medication, follow the protocol, or that would make participation not in the best interest of the participant, per the site investigator.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p style=\"margin-left:1.0in;\">\n Requirement for taking any of the prohibited medications with the selected ARV study regimen, or within 14 days prior to study entry (see section 5.4.2).</p>\n<p>\n  </p>\n<p style=\"margin-left:1.0in;\">\n Active tuberculosis (TB) or rifampin exposure less than 2 weeks prior to study entry. </p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<h2>\n Exclusion Criteria for Step 2</h2>\n<p>\n Contraindication to the proposed Step 2 ARV regimen as determined by the site investigator.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<h2>\n Exclusion Criteria for Step 3</h2>\n<h2>\n <span style=\"font-size: 12px;\">Indication for discontinuation of RAL, ETR, or DRV.</span></h2>\n
      • primary_end_points<p>\n Treatment Failure</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • 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<div>\n Dr. Mumbi Makanga</div>\n<div>\n MBChB, MPH</div>\n<div>\n Principal Investigator and Study Medical Officer,</div>\n<div>\n HIV Research Branch,</div>\n<div>\n KEMRI/CDC, (Kisumu)</div>\n<div>\n Will oversee daily study operations and implementation. Will supervise Kisumu-based study staff. Substantial input into site-specific study design, protocol development and assessment tools.</div>\n<div>\n Will provide patient management oversight, including clinical guidance on patient management, and medical care. Will guide study implementation, data analysis and report writing. Will be a member of the protocol team.</div>\n<div>\n  </div>\n<div>\n <div>\n Clement Zeh</div>\n <div>\n PhD, MPH</div>\n <div>\n Co-Principal Investigator,</div>\n <div>\n HIV Research Branch,</div>\n <div>\n CDC Kenya (Kisumu)</div>\n <div>\n Will provide input for data analysis and will write report. Will be a member of the protocol team with substantial input into site-specific study design, protocol development and assessment tools. Will assist with study implementation, data analysis and report writing.</div>\n <div>\n  </div>\n <div>\n <div>\n Dr. Victor Mudhune</div>\n <div>\n BPharm, MBA, MPH(c)</div>\n <div>\n Co-Principal Investigator and Study Pharmacist,</div>\n <div>\n HIV Research Branch,</div>\n <div>\n KEMRI/CDC, (Kisumu)</div>\n <div>\n Will provide input for data analysis and will be a member of the protocol team with substantial input into site-specific study design, protocol development and assessment tools. Will oversee all pharmaceutical aspects of the study and maintain oversight of study drugs. Will provide input for study implementation, data analysis and report writing. Will be a member of the protocol team.</div>\n <div>\n  </div>\n <div>\n <div>\n Fredrick Otieno</div>\n <div>\n MPH, PhD(c)</div>\n <div>\n Co-Investigator</div>\n <div>\n HIV Research Branch,</div>\n <div>\n KEMRI/CDC, (Kisumu)</div>\n <div>\n Will provide substantial input into site-specific study design, protocol development and assessment tools. Will guide study implementation, data analysis and report writing. Will be a member of the protocol team.</div>\n <div>\n  </div>\n <div>\n <div>\n Taraz Samandari</div>\n <div>\n MD, PhD.</div>\n <div>\n Co-Investigator</div>\n <div>\n CDC ,Atlanta</div>\n <div>\n Will provide support for study from CDC Atlanta, including liaison with ACTG. Will provide substantial input into protocol development. Will guide study implementation, data analysis and report writing. Will be a member of the protocol team.</div>\n <div>\n  </div>\n <div>\n <div>\n Robert T. Chen</div>\n <div>\n MD, MA</div>\n <div>\n Co-Investigator</div>\n <div>\n CDC, Atlanta</div>\n <div>\n Will provide support for study from CDC Atlanta, including liaison with ACTG. Will provide substantial input into site-specific study design, protocol development and assessment tools. Will guide study implementation, data analysis and report writing. Will be a member of the protocol team.</div>\n <div>\n  </div>\n <div>\n <div>\n Allan Taylor</div>\n <div>\n MD, MPH</div>\n <div>\n Co-investigator</div>\n <div>\n CDC, Atlanta</div>\n <div>\n Will provide substantial input into site-specific study design, protocol development and assessment tools. Will guide study implementation, data analysis and report writing. Will be a member of the protocol team.</div>\n <div>\n  </div>\n <div>\n <div>\n Susan Danner</div>\n <div>\n Co-investigator and Study coordinator</div>\n <div>\n CDC, Atlanta</div>\n <div>\n Will provide substantial input into site-specific study design, protocol development and assessment tools. Will guide study implementation, data analysis and report writing. Will be a member of the protocol team. Will coordinate study issues and communications between CDC Atlanta and field sites.</div>\n <div>\n  </div>\n <div>\n <div>\n John Okanda</div>\n <div>\n BSc, MPH(c)</div>\n <div>\n Study Coordinator</div>\n <div>\n HIV Research Branch,</div>\n <div>\n KEMRI/CDC, (Kisumu)</div>\n <div>\n Will coordinate all field components of the study, will interact daily with the study participants, study team and investigators, will provide input for study implementation, data analysis and report writing.</div>\n <div>\n  </div>\n <div>\n <div>\n Collin Odhiambo</div>\n <div>\n MSc, PhD(c)</div>\n <div>\n Laboratory Lead,</div>\n <div>\n HIV Research Branch,</div>\n <div>\n KEMRI/CDC, (Kisumu)</div>\n <div>\n Will oversee all laboratory aspects of the study and maintain oversight of laboratory procedures. Will provide input for study implementation, data analysis and report writing. Will be a member of the protocol team.</div>\n <div>\n  </div>\n <div>\n <div>\n Richard Ndivo</div>\n <div>\n MSc</div>\n <div>\n Lead Data Manager,</div>\n <div>\n HIV Research Branch,</div>\n <div>\n KEMRI/CDC (Kisumu)</div>\n <div>\n Will oversee all data aspects of this study and will be involved in all site-specific data analysis and report writing. Will be a member of the protocol team.</div>\n <div>\n  </div>\n <div>\n <div>\n Elizabeth Ayuo</div>\n <div>\n BA</div>\n <div>\n Lead Regulatory officer</div>\n <div>\n HIV Research Branch,</div>\n <div>\n KEMRI/CDC (Kisumu)</div>\n <div>\n Will provide guidance and oversight over all of the regulatory aspects of this study, including quality assurance and quality control, and ensure that all staff are GCP trained and compliant. Will be a member of the protocol team.</div>\n <div>\n  </div>\n <div>\n <div>\n Ken Ondenge</div>\n <div>\n BA</div>\n <div>\n Lead Behavioral Scientist</div>\n <div>\n HIV Research Branch,</div>\n <div>\n KEMRI/CDC (Kisumu)</div>\n <div>\n Will provide guidance and oversight over all of the qualitative aspects of this study and will be involved in site-specific study implementation with regard to liaising with all stakeholders/community. Will be a member of the protocol team.</div>\n <div>\n  </div>\n <div>\n <div>\n Frank Angira</div>\n <div>\n MPH(c)</div>\n <div>\n Clinician</div>\n <div>\n HIV Research Branch,</div>\n <div>\n KEMRI/CDC (Kisumu)</div>\n <div>\n Will provide guidance into site specific study implementation, and contribution to site specific protocol development.</div>\n <div>\n  </div>\n <div>\n <div>\n Arthur Ogendo</div>\n <div>\n BA, MPH(c)</div>\n <div>\n Social Scientist</div>\n <div>\n HIV Research Branch,</div>\n <div>\n KEMRI/CDC (Kisumu)</div>\n <div>\n Will provide guidance into site specific study implementation, and significant contribution to site specific protocol development.</div>\n <div>\n  </div>\n <div>\n <div>\n Carren Amondi</div>\n <div>\n BBA</div>\n <div>\n Administrative Officer,</div>\n <div>\n HIV Research Branch,</div>\n <div>\n KEMRI/CDC Kenya (Kisumu)</div>\n <div>\n Will provide oversight of all administrative aspects of this study, including budget</div>\n </div>\n </div>\n </div>\n </div>\n </div>\n </div>\n </div>\n </div>\n </div>\n </div>\n </div>\n </div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The study sponsors are based in the united states.The study is restricted to limited resource setting, and the implementing countries are thus considered as such. As at 27 June 2014, the study had enrolled participants across all participating sites, which include the following:</p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:632px;\" width=\"632\">\n <tbody>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:82px;height:20px;\">\n <p>\n <strong>Country</strong></p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:105px;height:20px;\">\n <p>\n <strong>City</strong></p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:162px;height:20px;\">\n <p>\n <strong>Research Site</strong></p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:186px;height:20px;\">\n <p>\n <strong>Clinical trial Unit Name</strong></p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:97px;height:20px;\">\n <p>\n <strong>Date Activated</strong></p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:82px;height:20px;\">\n <p>\n Peru</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:105px;height:20px;\">\n <p>\n Lima</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:162px;height:20px;\">\n <p>\n Barrancos CRS</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:186px;height:20px;\">\n <p>\n IMPACTA PERU CTU</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:97px;height:20px;\">\n <p align=\"right\">\n 9-Jul-12</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:82px;height:44px;\">\n <p>\n India</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:105px;height:44px;\">\n <p>\n Chennai</p>\n </td>\n <td style=\"width:162px;height:44px;\">\n <p>\n Chennai Antiviral research and treatment CRS</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:186px;height:44px;\">\n <p>\n University of California CTU</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:97px;height:44px;\">\n <p align=\"right\">\n 28-Apr-14</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:82px;height:40px;\">\n <p>\n Thailand</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:105px;height:40px;\">\n <p>\n Chiang Mal</p>\n </td>\n <td style=\"width:162px;height:40px;\">\n <p>\n Chiang Mai University HIV treatment CRS</p>\n </td>\n <td style=\"width:186px;height:40px;\">\n <p>\n Thailand HIV/AIDS and Infectious disease CTU</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:97px;height:40px;\">\n <p align=\"right\">\n 9-Oct-12</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:82px;height:60px;\">\n <p>\n Brazil</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:105px;height:60px;\">\n <p>\n Rio de Janeiro</p>\n </td>\n <td style=\"width:162px;height:60px;\">\n <p>\n Instututo de Pesquisa Clinica Evandra Chagas CRS</p>\n </td>\n <td style=\"width:186px;height:60px;\">\n <p>\n The Fiocruz Therapeutic and prevention HIV/AIDS CTU</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:97px;height:60px;\">\n <p align=\"right\">\n 18-Jan-13</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:82px;height:40px;\">\n <p>\n Uganda</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:105px;height:40px;\">\n <p>\n Kampala</p>\n </td>\n <td style=\"width:162px;height:40px;\">\n <p>\n Joint Clinical Research Centre /Kampala CRS</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:186px;height:40px;\">\n <p>\n Case CTU</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:97px;height:40px;\">\n <p align=\"right\">\n 15-May-13</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:82px;height:63px;\">\n <p>\n Malawi</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:105px;height:63px;\">\n <p>\n Lilongwe</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:162px;height:63px;\">\n <p>\n Malawi CRS</p>\n </td>\n <td style=\"width:186px;height:63px;\">\n <p>\n University of North Carolina Global HIV prevention and treatment CTU</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:97px;height:63px;\">\n <p align=\"right\">\n 12-Oct-12</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:82px;height:40px;\">\n <p>\n Kenya</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:105px;height:40px;\">\n <p>\n Eldoret</p>\n </td>\n <td style=\"width:162px;height:40px;\">\n <p>\n Moi University CRS</p>\n </td>\n <td style=\"width:186px;height:40px;\">\n <p>\n United States Military HIV Research Program CTU</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:97px;height:40px;\">\n <p align=\"right\">\n 14-Jun-13</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:82px;height:40px;\">\n <p>\n Zimbabwe</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:105px;height:40px;\">\n <p>\n Harare</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:162px;height:40px;\">\n <p>\n Parirenyatwa CRS</p>\n </td>\n <td style=\"width:186px;height:40px;\">\n <p>\n University of Zimbabwe / University of California CTU</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:97px;height:40px;\">\n <p align=\"right\">\n 6-Aug-13</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:82px;height:20px;\">\n <p>\n Peru</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:105px;height:20px;\">\n <p>\n Lima</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:162px;height:20px;\">\n <p>\n San Miguel CRS</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:186px;height:20px;\">\n <p>\n IMPACTA PERU CTU</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:97px;height:20px;\">\n <p align=\"right\">\n 31-Jul-12</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:82px;height:40px;\">\n <p>\n South Africa</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:105px;height:40px;\">\n <p>\n Johannesburg</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:162px;height:40px;\">\n <p>\n Soweto CRS</p>\n </td>\n <td style=\"width:186px;height:40px;\">\n <p>\n Soweto Clinical Trials Unit for NIAID CTU</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:97px;height:40px;\">\n <p align=\"right\">\n 24-Oct-12</p>\n </td>\n </tr>\n <tr>\n <td nowrap=\"nowrap\" style=\"width:82px;height:40px;\">\n <p>\n South Africa</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:105px;height:40px;\">\n <p>\n Johannesburg</p>\n </td>\n <td style=\"width:162px;height:40px;\">\n <p>\n University of Witwatersrand CRS</p>\n </td>\n <td style=\"width:186px;height:40px;\">\n <p>\n University of Witwatersrand CTU</p>\n </td>\n <td nowrap=\"nowrap\" style=\"width:97px;height:40px;\">\n <p align=\"right\">\n 18-Sep-12</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n Source: ACTG network website, <a href=\"http://www.actgnetwork.org/\">www.actgnetwork.org</a> on 29Jul2014</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_regulatory_notapproved<p>\n NONE</p>\n
      • other_details_regulatory_approved<p>\n KEMRI SSC</p>\n<p>\n KEMRI ERC</p>\n<p>\n CDC IRB (with reliance on KEMRI)</p>\n
      • other_details_regulatory_rejected<p>\n NONE</p>\n
      • other_details_regulatory_halted<p>\n NONE</p>\n
      • estimated_duration3.5 years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatoralternative ART regimens
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI/CDC CLINICAL RESEARCH CENTRE
      • single_site_physical_addressWITHING JARAMOGI OGINGA ODINGA TEACHING & REFERRAL HOSPITAL
      • single_site_contact_personDr. Kevin Cain
      • single_site_telephone+254-57-2022929
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states10
      • number_of_sites
      • multi_country_listPeru, India, Thailand, Brazil, Uganda, Malawi, Zimbabwe, South Africa, kenya
      • data_monitoring_committeeYes
      • total_enrolment_per_site50
      • total_participants_worldwide500
      • 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_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • 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_nameJeffrey
      • investigator1_middle_name
      • investigator1_family_nameLennox
      • investigator1_qualificationMD
      • investigator1_professional_addressEmory University
      • investigator1_telephone404-251-8784
      • investigator1_emailJLennox@emory.edu
      • organisations_transferred_No
      • number_participants50
      • notification
      • approval_date08-09-2014
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted06-08-2014
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n The title of the study was “Management Using the Latest Technologies in Resource-Limited Settings to Optimize Combination Therapy After Viral Failure (MULTI-OCTAVE)”</p>\n<p>\n The main purpose of this study was to evaluate the ability of novel agents and contemporary management tools to achieve a ≥65% rate of virologic control at 48 weeks of follow-up in HIV-infected persons presenting with second-line antiretroviral treatment failure. The novel agents were: etravirine (ETR), raltegravir (RAL), and ritonavir-boosted darunavir (DRV/r). The contemporary management tools included standard genotyping at screening and in the case of virologic failure (VF) to select an appropriate regimen, interventions to improve adherence, and plasma viral load (VL) monitoring.</p>\n<p>\n From Jan 10, 2013, to Sept 10, 2015, 545 participants were enrolled in the study. At enrollment, drug resistance (moderate or high-level) to 0, 1, 2, and 3 ARV classes was identified in 22%, 20%, 30% and 27% of participants, respectively. Overall, 349 (64%, 95% CI 60, 68%) of study participants had VL ≤200 copies/mL at week 48. Viral suppression and VF differed across cohorts (see Table below). By week 48, Cohort A had the most Grade ≥3 adverse events (39%) and regimen discontinuations (13%). No differences in VL ≤200 copies/mL at week 48 or VF ≥24 weeks were observed in the randomized comparison of B1 & B2 cohorts. </p>\n<p>\n  </p>\n<p>\n Regimens containing DRV/r and RAL with or without ETR were highly effective for participants with resistance to ritonavir-boosted lopinavir (LPV/r) who presented for 3rd line ART. More than half of participants without LPV/r resistance who remained on 2nd line ART did not achieve sustained viral suppression at week 48. This subgroup requires additional interventions to achieve viral suppression. This study was not designed or powered with the intent of comparing outcomes between the various resistance groups. Targeted real-time genotyping to select regimens for 3rd line ART can appropriately allocate more costly ARVs to those with greater resistance.</p>\n<p>\n The manuscript was published in the lancet with the following details;</p>\n<p>\n Beatriz Grinsztejn, Michael D Hughes, Justin Ritz et al. <em>Third-line antiretroviral therapy in low-income and middle-income countries (ACTG A5288): a prospective strategy study. </em>Lancet HIV, July 29, 2019 http://dx.doi.org/10.1016/S2352-3018(19)30146-8</p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\">\n <tbody>\n <tr>\n <td colspan=\"4\" style=\"width:392px;height:22px;\">\n <p align=\"center\">\n <strong>Cohort Information</strong></p>\n </td>\n <td colspan=\"2\" style=\"width:247px;height:22px;\">\n <p align=\"center\">\n <strong>Results</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:68px;height:51px;\">\n <p align=\"center\">\n <strong>Cohort</strong></p>\n </td>\n <td style=\"width:142px;height:51px;\">\n <p align=\"center\">\n <strong>Definition</strong></p>\n </td>\n <td style=\"width:104px;height:51px;\">\n <p align=\"center\">\n <strong>Regimen Summary</strong></p>\n </td>\n <td style=\"width:78px;height:51px;\">\n <p align=\"center\">\n <strong># (%)</strong></p>\n </td>\n <td style=\"width:114px;height:51px;\">\n <p align=\"center\">\n <strong># (%) ≤200 copies/mL at Wk 48</strong></p>\n </td>\n <td style=\"width:133px;height:51px;\">\n <p align=\"center\">\n <strong># (%) confirmed virologic failure</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:68px;height:34px;\">\n <p align=\"center\">\n A</p>\n </td>\n <td style=\"width:142px;height:34px;\">\n <p align=\"center\">\n No LPV/r resistance Susceptible to <u>></u>1 NRTI</p>\n </td>\n <td style=\"width:104px;height:34px;\">\n <p align=\"center\">\n Continue 2^{<font size=\"2\">nd</font>} line ART</p>\n </td>\n <td style=\"width:78px;height:34px;\">\n <p align=\"center\">\n 287 (53%)</p>\n </td>\n <td style=\"width:114px;height:34px;\">\n <p align=\"center\">\n 125 (44%)</p>\n </td>\n <td style=\"width:133px;height:34px;\">\n <p align=\"center\">\n 145 (51%)</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:68px;\">\n <p align=\"center\">\n B1</p>\n </td>\n <td rowspan=\"3\" style=\"width:142px;\">\n <p align=\"center\">\n  </p>\n <p align=\"center\">\n Resistant to LPV/r, susceptible to DRV/r & ETR</p>\n <p align=\"center\">\n *B3 HBV Ag +</p>\n </td>\n <td style=\"width:104px;\">\n <p align=\"center\">\n Best available NRTIs + DRV/r + RAL</p>\n </td>\n <td style=\"width:78px;\">\n <p align=\"center\">\n 74 (14%)</p>\n </td>\n <td style=\"width:114px;\">\n <p align=\"center\">\n 65 (88%)</p>\n </td>\n <td style=\"width:133px;\">\n <p align=\"center\">\n 6 (8%)</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:68px;\">\n <p align=\"center\">\n B2</p>\n </td>\n <td style=\"width:104px;\">\n <p align=\"center\">\n DRV/r + RAL + ETR</p>\n </td>\n <td style=\"width:78px;\">\n <p align=\"center\">\n 72 (13%)</p>\n </td>\n <td style=\"width:114px;\">\n <p align=\"center\">\n 63 (88%)</p>\n </td>\n <td style=\"width:133px;\">\n <p align=\"center\">\n 4 (6%)</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:68px;\">\n <p align=\"center\">\n B3</p>\n </td>\n <td style=\"width:104px;\">\n <p align=\"center\">\n DRV/r + RAL + TDF/FTC or TDF+3TC</p>\n </td>\n <td style=\"width:78px;\">\n <p align=\"center\">\n 8 (1%)</p>\n </td>\n <td style=\"width:114px;\">\n <p align=\"center\">\n 8 (100%)</p>\n </td>\n <td style=\"width:133px;\">\n <p align=\"center\">\n 0 (0%)</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:68px;\">\n <p align=\"center\">\n C</p>\n </td>\n <td style=\"width:142px;\">\n <p align=\"center\">\n Resistant to LPV/r & ETR but susceptible to DRV/r; no prior RAL</p>\n </td>\n <td style=\"width:104px;\">\n <p align=\"center\">\n Best available NRTIs +  DRV/r + RAL</p>\n </td>\n <td style=\"width:78px;\">\n <p align=\"center\">\n 70 (13%)</p>\n </td>\n <td style=\"width:114px;\">\n <p align=\"center\">\n 63 (90%)</p>\n </td>\n <td style=\"width:133px;\">\n <p align=\"center\">\n 5 (7%)</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:68px;height:33px;\">\n <p align=\"center\">\n D</p>\n </td>\n <td style=\"width:142px;height:33px;\">\n <p align=\"center\">\n Not eligible for Cohorts A, B, or C</p>\n </td>\n <td style=\"width:104px;height:33px;\">\n <p align=\"center\">\n Best available local & study supplied ARVs</p>\n </td>\n <td style=\"width:78px;height:33px;\">\n <p align=\"center\">\n 34 (6%)</p>\n </td>\n <td style=\"width:114px;height:33px;\">\n <p align=\"center\">\n 25 (74%)</p>\n </td>\n <td style=\"width:133px;height:33px;\">\n <p align=\"center\">\n 6 (18%)</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n
      • implication_results<p style=\"margin: 0px 0px 11px; text-align: justify;\">\n <span lang=\"EN-US\" style=\"margin: 0px;\">Targeted real-time HIV-1 drug resistance testing is a useful treatment management tool for ensuring appropriate allocation of expensive third line drug options. The combination of darunavir and raltegravir with either etravirine or recycled NRTIs is highly effective and safe for individuals in diverse LMICs who experienced second-line therapy failure with resistance to lopinavir. For individuals on failing second-line ART without resistance to lopinavir and limited resistance to NRTIs, better tolerated second-line regimens and adherence interventions will be needed to improve treatment outcomes. </span></p>\n<p>\n  </p>\n
      • quantity_importedNil to all medications
      • quantity_dispensedMultiple medications . see spreadsheet attached
      • quantity_destroyedMultiple medications . see spreadsheet attached
      • quantity_exportedNil to all Medications
      • balance_siteMultiple medications . see spreadsheet attached
      • final_date0000-00-00
      • modified2021-01-27 09:30:54
      • created2014-08-05 14:51:29
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id217
        • application_id314
        • given_nameESTHER
        • middle_nameMUMBI
        • family_nameMAKANGA
        • qualificationMBChB
        • professional_addresskEMRI/ CDC, PO BOX 1578 - 40100, KISUMU
        • telephone057 2022902/59/02
        • emailmmakanga@kemricdc.org
        • created2014-08-05 15:23:29
        • modified2014-08-06 15:19:52
    • SiteDetail(array)
      • 0(array)
        • id267
        • application_id314
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2014-08-05 15:23:29
        • modified2014-08-06 15:19:52
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id174
        • application_id314
        • sponsorNational Institute of Allergy and Infectious Diseases, DAIDS
        • sponsor_type(null)
        • contact_personEileen Pouliot
        • address6700-B Rockledge Drive Room 3214, MSC 7612 Bethesda, Maryland 20892-7612
        • telephone_number+1-240-499-2239
        • fax_number
        • cell_number+1-240-499-2239
        • email_addressNIAIDOCSO@niaid.nih.gov
        • created2014-08-05 15:23:29
        • modified2014-08-06 15:19:52
  • 4(array)
    • Application(array)
      • id789
      • user_id522
      • trial_status_id5
      • abstract_of_study<p>\n <strong>Background</strong>: Induction of labor (IOL) has increasingly become a common procedure, more so in developed countries where the incidence currently averages 20-30%. In developing countries, IOL is variable ranging from 2% to as high as that seen in developed nations. In MTRH, about 5% of all deliveries are term inductions. Nulliparous women often comprise over half of those requiring IOL even in our setting. Additionally, the presence of an unfavorable cervix prior to induction is not uncommon in this group and is often associated with failed inductions, labor dystocia, caesarean sections and longer hospital stays. Hence the need for preinduction cervical ripening using a safe, efficient and cost effective method. This optimal method is not known. Recently, the concurrent use of Foley catheter (FC) with oxytocin for cervical ripening has been studied albeit in primarily Caucasian population. The findings have nonetheless been mixed.</p>\n<p>\n <strong>Objective</strong>: To determine whether adding low dose oxytocin to preinduction cervical ripening with a FC affects the time to delivery, proportion of deliveries within 24 hours and fetomaternal outcomes in nulliparous women at MTRH.</p>\n<p>\n <strong>Methods</strong>: This is a randomized double blind placebo controlled trial to be conducted at the Riley Mother and Baby hospital in MTRH. 220 nulliparous women aged at least 18 years with a single, live, vertex pregnancy and scheduled for IOL with an unfavorable cervix at or beyond 34 weeks gestation will be systematically sampled for inclusion in the study. Consenting participants will be allocated to receive FC plus low dose oxytocin or FC plus placebo using block randomisation, with a block size of 20. The primary and secondary endpoints will be at delivery and 24 hours post-delivery respectively. Data will be collected using semi-structured data collection forms and entered into an electronic database using Microsoft Access. Categorical variables will be summarized using frequencies and percentages. Continuous variables will be summarized using mean and the corresponding standard deviation (SD) if the Gaussian assumptions hold or using median and the corresponding inter quartile range (IQR) if the Gaussian assumptions are violated. The time to delivery will be compared between the two arms using independent t-test if the Gaussian assumptions hold or using the two sample Wilcoxon rank-sum test if the Gaussian assumptions are violated. Categorical variables will be compared between the two arms using Pearson’s Chi Square test. Linear regression model will be used to assess the effect of Foley catheter plus oxytocin adjusting for potential confounding variables. We shall report the regression coefficients and the corresponding 95% confidence intervals. Results will be presented using tables and graphs. Data analysis will be done using SAS version 9.4.</p>\n<p>\n <strong>Expected findings:</strong> The time to delivery has a potentially significant impact on resources and obstetric outcomes. Our study seeks to establish the impact of concurrent FC and oxytocin on the time to delivery and the safety of the same in nulliparous women undergoing cervical ripening in our setting. This will robustly complement previous studies and ultimately inform future protocols with rational, objective and evidence based data.</p>\n
      • study_title<p>\n LOW DOSE OXYTOCIN AS AN ADJUNCT TO FOLEY CATHETER FOR CERVICAL RIPENING IN NULLIPAROUS WOMEN AT MTRH, ELDORET, KENYA: A RANDOMISED CONTROLLED TRIAL.</p>\n
      • laymans_summary(null)
      • short_titleLOxaF- N Trial
      • protocol_noECCT/19/08/02
      • version_no1
      • date_of_protocol26-09-2018
      • study_drugOxytocin
      • disease_conditionRipening of the cervix
      • 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_nameSyntocinon
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresspatrickomondi_md@yahoo.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_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_applicantPatrick Omondi Otieno
      • declaration_date123-06-2019
      • declaration_principal_investigatorDr Patrick Omondi
      • declaration_date223-06-2019
      • placebo_presentYes
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n a. Nulliparous women at or beyond 34+0 weeks gestation from the LMP b. At least 18 years old c. Single, live and vertex fetus d. Written informed consent</p>\n
      • principal_exclusion_criteria<p>\n a. Admission Bishop score > 6</p>\n<p>\n b. Sonographically confirmed anomalous fetus.</p>\n<p>\n c. Prelabor rupture of membranes (PROM)</p>\n<p>\n d. Suspected intraamniotic infection</p>\n<p>\n e. Intrauterine fetal demise</p>\n<p>\n f. Any contraindication to vaginal delivery</p>\n<p>\n g. Scarred uterus</p>\n
      • primary_end_points<p>\n Delivery of the fetus.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • 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_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n MTRH is a level 6 tertiary referral health facility in Eldoret, Uasin Gishu county. The RMBH has 4 wards namely; antenatal ward (ANW), postnatal ward (PNW) and labor ward (L/W) where women in active phase of labor are admitted for monitoring and delivery. The RMBH unit is staffed by about 16 consultant obstetrician/gynecologists from both Moi University and MTRH, 46 residents/registrars and 88 nurses/midwives.</p>\n
      • other_details_explanation<p>\n Not Applicable</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n The Moi University/MTRH Institutional research and ethics commitee - 26/09/2018</p>\n<p>\n The Moi Teaching and Referral Hospital - 02/10/2018</p>\n
      • other_details_regulatory_rejected<p>\n None.</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable</p>\n
      • estimated_duration1 year
      • 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_comparatorPlacebo (Water for inject
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaThe Riley Mother and Baby Hospital (RMBH) at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya.
      • single_site_physical_address-
      • single_site_contact_personPatrick Omondi Otieno
      • single_site_telephone0731226249
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteNot applicable
      • total_participants_worldwideNot Applicable
      • 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_male0
      • subjects_healthyYes
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenYes
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameOtieno
      • investigator1_middle_nameOmondi
      • investigator1_family_namePatrick
      • investigator1_qualificationBachelor of Medicine and Bachelor of Surgery (MBchB)
      • investigator1_professional_address4606-30101, Eldoret, Uasin Gishu County, Kenya.
      • investigator1_telephone+254731226249
      • investigator1_emaildoc_omondi@yahoo.com
      • organisations_transferred_No
      • number_participants220 at Single study site
      • notification<p>\n N/A</p>\n
      • approval_date01-10-2019
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted25-08-2019
      • 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)
      • modified2021-11-09 18:21:07
      • created2019-04-16 13:31:05
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id492
        • application_id789
        • given_namePatrick Omondi
        • middle_name
        • family_nameOtieno
        • qualificationMBChB
        • professional_address4606-30100
        • telephone0731226249
        • emaildoc_omondi@yahoo.com
        • created2019-04-16 13:55:47
        • modified2019-08-25 21:19:15
    • SiteDetail(array)
      • 0(array)
        • id637
        • application_id789
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2019-04-16 13:55:47
        • modified2019-08-25 21:19:15
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id384
        • application_id789
        • sponsorSelf
        • sponsor_type(null)
        • contact_personPatrick Omondi Otieno
        • address4606-30100
        • telephone_number0731226249
        • fax_number
        • cell_number0731226249
        • email_addressdoc_omondi@yahoo.com
        • created2019-04-16 13:55:47
        • modified2019-08-25 21:19:15
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(empty)
• $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

App Constants

CakePHP Constants

PHP Environment

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)
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    • 1CORE/Model/Datasource/Database/Mysql.php
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    • 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