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• applications(array)
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    • Application(array)
      • id153
      • user_id21
      • trial_status_id5
      • abstract_of_study<p>\n <strong>Design</strong>: A 2x2x2 open-label factorial multi-centre trial, conducted in 9 centres in 4 countries (Kenya, Malawi, Uganda, Zimbawe)</p>\n<p>\n <strong>Participants:</strong> 1800 HIV-infected patients including adults, adolescents and children aged 5 years or older with low CD4 counts about to initiate combination antiretroviral therapy (ART). At the Eldoret site, 250 participants will be enrolled.</p>\n<p>\n <strong>Intervention</strong>: Three methods to reduce early mortality following ART initiation</p>\n<p style=\"margin-left: 40px;\">\n (i) increasing the potency of ART with a 12 week induction period using 4 antiretroviral drugs from 3 classes<br />\n (ii) augmented prophylaxis against opportunistic/bacterial infections and helminths for 12 weeks<br />\n (iii) macronutrient intervention using ready-to-use supplementary food for 12 weeks.</p>\n<p>\n Each intervention will be compared with standard of care, which in previously untreated patients presenting late with very low CD4 counts is to initiate ART with 3 drugs from 2 classes, together with cotrimoxazole prophylaxis and macronutrient intervention only for those with low BMI (or low weight-for-height/mid-upper arm<br />\n circumference in children).</p>\n<p>\n <strong>Duration</strong>:
        </p>\n<ul>\n <li>\n Participants will be randomised over 1.5-2 years.</li>\n <li>\n
        Each intervention will be administered in addition to standard of care for 12 weeks.</li>\n <li>\n
        Each participant will be followed for 48 weeks in the trial.</li>\n <li>\n
        The overall trial duration is 3 years.</li>\n</ul>\n
      • study_title<p>\n Reduction of EArly mortaLITY in HIVinfected adults and children starting antiretroviral therapy (REALITY)</p>\n
      • laymans_summary(null)
      • short_titleReduction of EArly mortaLITY in adults and children
      • protocol_noECCT/12/09/02
      • version_no1.01
      • date_of_protocol04-04-2012
      • study_drugRaltegravir
      • 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_nameIsentress
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressaksudoi@hotmail.com
      • applicant_covering_letter1
      • applicant_protocol1
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      • declaration_applicantAllan K Sudoi
      • declaration_date112-06-2013
      • declaration_principal_investigatorAbraham M Siika, MBChB, MMed, Msc - Site Principal Investigator
      • declaration_date212-06-2013
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n 1. Aged 5 years or older<br />\n 2. Documented HIV infection by HIV ELISA or HIV rapid test<br />\n 3. Naive to ART<br />\n 4. CD4 T-cell count <100 cells/mm3 on blood test taken at screening for REALITY<br />\n 5. Results of screening haematology and biochemistry tests available and no contraindications to planned ART according to national guidelines<br />\n 6. Patient/carer provide informed consent (and children <18 years assent, as appropriate according to their age and knowledge of HIV status)</p>\n<p>\n The lower age limit is because CD4 counts are less reliable predictors of immunodeficiency under 5 years: CD4 counts are recommended by guidelines in older children.<br />\n No patient with a CD4 count above 100 cells/mm3 should have ART delayed in order to subsequently meet eligibility criteria. Rather, patients eligible for REALITY will be those testing HIV positive for the first time with a low CD4 count (i.e. those delaying presentation to care), or those who have defaulted before initiating ART and only return to care at an advanced stage of immuno-deficiency.</p>\n
      • principal_exclusion_criteria<p>\n 1. Contraindications to any proposed antiretroviral drugs (including integrase inhibitors), isoniazid, fluconazole, albendazole or azithromycin<br />\n 2. Pregnant or breastfeeding or intending to become pregnant during the first 12 weeks of the study<br />\n 3.. Ever known to have previously received single-dose nevirapine for prevention of mother-to-child transmission (mother or child).</p>\n
      • primary_end_points<p>\n All-cause mortality over the first 24 weeks after starting ART</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic1
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      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Abraham M. Siika MBChB, MMed, MS- Site Leader/ Principal Investigator</p>\n<p>\n Kara Wools-Kaloustian MD- Co-investigator</p>\n<p>\n Winston M Nyandiko, MBChB,MMed- Co-investigator</p>\n<p>\n Priscilla Cheruiyot, BScN, MPH- Site Coordinator</p>\n<p>\n Charles Kwobah, MBChB- Medical Officer</p>\n<p>\n Mercy Karoney  MBChB- Medical Officer</p>\n<p>\n Simon Wachira Njuguna, B Pharm, MPSK - Pharmacist of Record</p>\n<p>\n Kipruto Kirwa, BSc, MPH, PhD- Quality Manager</p>\n<p>\n Martha Mokaya, BSc, MBA- Data Manager</p>\n<p>\n Wilson Lokitala Ekiru, BSc IT- Assistant Data Manager</p>\n<p>\n Agnes M. Nzioka, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Betty Meli, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Michael Tanui, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Julie Choge -  Recruitment Officer</p>\n<p>\n Amina Msuo Shali - Recruitment Officer</p>\n<p>\n Dorothy Mwimali -  Recruitment Officer</p>\n<p>\n Cecilia Chebet, Dip Counselling - Recruitment Officer</p>\n<p>\n Beatrice Jakait, B Pharm- Back-up Pharmacist</p>\n<p>\n Chris Sande, KHRCN- Study Nurse</p>\n
      • other_details_explanation<p>\n Whilst WHO guidelines now advocate earlier initiation of ART in HIV-infected adults and children 5 years or older at <350 rather than <200 cells/mm3, in clinical practice, substantial numbers continue to present for care late in HIV infection - in both resource-rich and resource-limited settings. Given experience in resource-rich countries, this will continue to be a feature of ART rollout programmes for the forseeable future. However, the consequences of such late presentation, in terms of early morbidity/mortality on ART, are far more severe in resource-limited settings. To maximise benefits of ART, it is essential to identify which interventions, if any, in addition to ART could reduce high early death rates. Data from both adults and older children demonstrate the highest early mortality in those initiating ART with CD4 cell counts <50 cells/mm3 (see Section 1.1 of the protocol): early mortality rates approximately halve in those with CD4 cell counts 50-99 cells/mm3 and halve again with pre-ART CD4 cell counts >100 cells/mm3. Thus those with CD4 <100 cells/mm3 have substantial risks, and present in sufficient numbers, that interventions of proven benefit in this group could rapidly improve ART outcomes.</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n Moi Teaching and Referral Hospital/Moi University Institutional Research and Ethics Committee (IREC). Approval granted on 20 June 2012.</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationPArticipants will be randomized over 1.5 to 2 years. The overall study will take three 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_comparatorStandard 2 NRTI+NNRTI plu
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specifyIsoniazid, Fluconazole, Azithromycin,Albendazole
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites2
      • multi_country_listZimbabwe, Uganda, Malawi, Kenya
      • data_monitoring_committeeYes
      • total_enrolment_per_site250 at Eldoret Site
      • total_participants_worldwide1800
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameAnthony
      • investigator1_middle_name
      • investigator1_family_nameEtyang
      • investigator1_qualificationMBChB
      • investigator1_professional_addressKEMRI Wellcome Trust Research Programme PO BOX 230 Kilifi, 80108 Kenya.
      • investigator1_telephone+ 254 41 752 2063
      • investigator1_emailAetyang@kilifi.kemri-wellcome.org
      • organisations_transferred_No
      • number_participants250 at Eldoret Site (200 adults and 50 Children)
      • notification
      • approval_date04-04-2012
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted12-06-2013
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2018-03-26 12:24:16
      • created2013-06-11 12:27:30
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id97
        • application_id153
        • given_nameAbraham
        • middle_nameMosigisi
        • family_nameSiika
        • qualificationMBChB, MMed, MSc
        • professional_addressP O Box, 4606-30100, Eldoret
        • telephone0721280785
        • emailamsiika@africaonline.co.ke
        • created2013-06-11 12:37:44
        • modified2013-06-12 16:38:34
    • SiteDetail(array)
      • 0(array)
        • id123
        • application_id153
        • county_id27
        • site_nameMoi University Clinical Research Centre
        • physical_addressAMPATH at MTRH, Nandi Road, Eldoret
        • contact_detailsP O Box 4606-30100, Eldoret
        • contact_personAllan Sudoi
        • site_capacity(null)
        • misc(null)
        • created2013-06-11 12:37:44
        • modified2013-06-12 16:38:34
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
      • 1(array)
        • id124
        • application_id153
        • county_id3
        • site_nameKEMRI Wellcome Trust Research Programme
        • physical_addressKilifi
        • contact_detailsPO BOX 230 Kilifi, 80108 Kenya
        • contact_personDr Anthony Etyang
        • site_capacity(null)
        • misc(null)
        • created2013-06-11 13:02:53
        • modified2013-06-12 16:38:34
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
    • Sponsor(array)
      • 0(array)
        • id78
        • application_id153
        • sponsorMedical Research Council, UK
        • sponsor_type(null)
        • contact_personDirector, Regional Centre London
        • addressAviation House, 125 Kingsway, London
        • telephone_number+44 (0) 20 7670 4700
        • fax_number+44 (0) 20 7670 4816
        • cell_number+44 (0) 20 7670 4700
        • email_addressREALITY@ctu.mrc.ac.uk
        • created2013-06-11 12:37:44
        • modified2013-06-12 16:38:34
  • 1(array)
    • Application(array)
      • id215
      • user_id73
      • trial_status_id7
      • abstract_of_study<div>\n Antiretroviral-based HIV-1 prevention strategies – including</div>\n<div>\n 1) antiretroviral treatment (ART) to reduce the infectiousness of HIV-1 infected persons and</div>\n<div>\n 2) pre-exposure prophylaxis (PrEP) for uninfected persons to prevent HIV-1 acquisition – are among the most promising new approaches for dramatically decreasing HIV-1 spread. A priority population for implementation of ART and PrEP for HIV-1 prevention is HIV-1 serodiscordant couples (i.e., one member is HIV-1 infected and the other uninfected). Stable, heterosexual African HIV-1 serodiscordant couples face high risk of HIV-1 transmission, from within the partnership and from outside partners, and are a priority population for prevention interventions. Importantly, during the past year, both ART (HPTN 052) and PrEP (Partners PrEP Study) have demonstrated high efficacy for HIV-1 protection when used by members of HIV-1 serodiscordant couples. Critical unanswered questions for successful implementation of antiretroviral-based HIV-1 prevention include how to target these strategies to the highest-risk couples and whether HIV-1 infected persons with asymptomatic disease would accept ART to reduce their risk for transmitting HIV-1, at-risk HIV-1 negative persons would use PrEP, and both would sustain high adherence needed for high effectiveness. This protocol describes an open-label prospective study among high-risk African HIV-1 serodiscordant couples to determine user preferences for ART and PrEP and to optimize targeted delivery and sustained use of these interventions.</div>\n<div>\n  </div>\n<div>\n <strong>Design</strong>: Prospective, observational, open-label cohort study</div>\n<div>\n Up to <strong>24 months</strong> of follow-up per couple</div>\n<div>\n <strong>Population:</strong> Heterosexual HIV-1 serodiscordant couples in Kenya and Uganda who did not participate in the Partners PrEP Study (approximately 1000 couples in total)</div>\n<div>\n <strong>Study Sites</strong>: Thika, Kenya and Kampala, Uganda Partners PrEP Study sites</div>\n<div>\n Additional sites will be added if funding permits.</div>\n<div>\n <strong>Approach</strong>: We will enroll couples with characteristics defining higher HIV-1 transmission risk (i.e., to target those for ART/PrEP that are at greatest risk for HIV-1, a public health priority). We will provide or refer HIV-1 infected participants to ART services following national ART initiation guidelines, recognizing that guidelines for ART initiation (including potentially recommending ART for all HIV-1 infected members in serodiscordant relationships) may change during the course of the study. PrEP will be offered to the HIV-1 uninfected partners as a “bridge” to ART initiation and viral suppression in the partnership; uptake and adherence to PrEP will be measured. Specifically, PrEP as a bridge to ART will be done as follows: when the HIV-1 infected partner is not yet taking ART, PrEP will be offered, and if the HIV-1 infected partner initiates ART, PrEP will be discontinued for the HIV-1 uninfected partner six months later (i.e., once viral suppression in the HIV-1 infected partner would be expected to be typically achieved). We will conduct mixed-methods work to understand user preferences, couples decision-making, risk perception, fertility intentions, and barriers to uptake of and adherence to both PrEP and ART. </div>\n<div>\n  </div>\n<div>\n <span style=\"font-family:arial,helvetica,sans-serif;\"><strong>Specific Aims:</strong></span></div>\n<div>\n  </div>\n<div>\n <strong>Aim 1:</strong> <strong><u>We will evaluate the ability to do targeted enrollment of higher-risk HIV-1 serodiscordant couples into a longitudinal HIV-1 prevention study</u></strong></div>\n<div>\n  </div>\n<div>\n A critical aspect of implementation and cost-effectiveness of antiretroviral-based HIV-1 prevention in HIV-1 serodiscordant couples will be the ability to utilize behavioral, epidemiologic and clinical data to identify those couples who are at highest risk of HIV-1 acquisition. We have developed a risk score using enrollment data from our previous studies of >8500 HIV-1 serodiscordant couples that is able to discriminate couples at highest risk. The score is comprised of a limited set of variables that can be obtained in research and clinical settings: plasma HIV-1 levels in the HIV-1 infected partner, any unprotected sex in the couple in the prior month, number of children in the partnership, age of the HIV-1 uninfected partner, and circumcision status of HIV-1 uninfected male partners.</div>\n<div>\n The primary outcomes of this aim will be the screened to eligible ratio of HIV-1 serodiscordant couples recruited for this open-label study, the proportion of eligible couples who decide to enroll in the cohort, and the costs of screening and targeting high-risk couples.</div>\n<div>\n  </div>\n<div>\n <strong>Aim 2: <u>We will assess user preferences among high-risk HIV-1 serodiscordant couples for ART initiation for HIV-1 infected partners and PrEP for HIV-1 uninfected partners.</u></strong></div>\n<div>\n  </div>\n<div>\n Understanding couples’ preferences for and concerns about antiretroviral-based HIV-1 prevention is of utmost importance at this time when guidelines for use of PrEP and ART are being formulated.</div>\n<div>\n The primary outcomes for this aim will be measured at baseline and quarterly through an interviewer-administered questionnaire. The questionnaire will specifically ask about willingness to use PrEP or ART for HIV-1 prevention and which method the participant would prefer. Reasons for the choice and concerns about both methods will also be collected through mixed-methods approaches.</div>\n<div>\n  </div>\n<div>\n <strong>Aim 3: <u>We will ascertain initiation of and adherence to PrEP among HIV-1 uninfected partners, when implemented as a bridge to ART.</u></strong></div>\n<div>\n  </div>\n<div>\n Adherence to PrEP is critical to its effectiveness. Understanding adherence to PrEP is a priority, particularly when PrEP is delivered outside of a controlled clinical trial setting. For this study, brief adherence counseling, to reflect real-world settings, will be delivered at baseline and then quarterly thereafter. The content of the adherence counseling will be derived from the counseling messages and procedures in the Partners PrEP Study, and informed by the findings from an ancillary adherence study conducted as part of the Partners PrEP Study. We will explore factors that are related to the decision to start and continue to use PrEP.</div>\n<div>\n The primary measures of adherence will be collection of PrEP, clinic-based pill counts of unused study pills as recorded at each follow-up visit, and MEMS cap data on how frequently the pill bottle was opened. Blood samples for detection and quantification of PrEP levels (testing in batch) will be done for those who seroconvert to HIV-1 and a subset who remain HIV-1 uninfected.</div>\n<div>\n <strong>Aim 4: <u>We will ascertain initiation of and adherence to ART among HIV-1 infected partners.</u></strong></div>\n<div>\n  </div>\n<div>\n In addition to providing clinical benefit to HIV-1 infected partners, ART also confers HIV-1 prevention benefits to HIV-1 uninfected partners. However, a substantial proportion of HIV-1 infected persons who are eligible for ART decline or delay initiation, for a number of reasons. In this study, HIV-1 infected partners who become eligible for ART will be actively encouraged to initiate, including counseling to improve their knowledge and understanding of ART and the benefits for themselves and their partner and the importance of strict adherence to ART regimens to achieve viral suppression. We will explore factors that are related to the decision to start and continue to use ART.</div>\n<div>\n The primary measures of ART adherence will be ART initiation at a local ART provider and plasma HIV-1 RNA levels taken every 6 months for HIV-1 infected partners.</div>\n<div>\n  </div>\n<div>\n <strong>Aim 5: </strong><u><strong>We will assess factors influencing preferences, uptake and adherence for antiretroviral-based HIV-1 prevention.</strong></u></div>\n<div>\n  </div>\n<div>\n Understanding factors that influence couples’ preferences and their likelihood to initiate and adherence to PrEP and/or ART in a real-world setting is critical for providers who will counsel HIV-1 serodiscordant couples and make</div>\n<div>\n Partners PrEP Study Demonstration Project 6 Version 2.0, 10 July 2012</div>\n<div>\n recommendations about the HIV-1 prevention practices that are best indicated for couples.</div>\n<div>\n Through interviewer-administered questionnaires, correlates of preferences, uptake and adherence to ART and PrEP will be assessed, including characteristics of sexual risk (i.e., sexual frequency, condom use, whether the HIV-1 uninfected partner reports outside partners), depression and substance use, gender of the HIV-1 uninfected partner, fertility intentions, partnership characteristics (whether the couple is cohabiting, has children, is together throughout follow-up, whether members have other partners, and whether the HIV-1 infected partner initiates ART), and clinical characteristics of the HIV-1 infected partner (e.g., CD4 count, WHO stage).</div>\n<div>\n <strong>Aim 6: </strong><u><strong>We will assess the feasibility of PrEP discontinuation in couples in which the HIV-1 infected partner initiates ART</strong></u></div>\n<div>\n  </div>\n<div>\n ART is life-long, but PrEP need not be. In fact, time-limited use of PrEP for highest-risk persons and periods of time is likely the most cost-effective approach – since ART has substantial prevention benefits, any additional benefit of PrEP would be small for limiting risk within the partnership. Moreover, time-limited use of PrEP – e.g., until the HIV-1 infected partner initiates ART and is on ART for 6 months (the time by which viral suppression is typically achieved) – would limit risk of long-term side effects or toxicity of a daily PrEP medication and potentially improve adherence, since use would be for a defined period of time. Thus, time-limited use of PrEP has the greatest chance of being implemented widely. In couples in which the HIV-1 infected partner initiates ART, we will discontinue PrEP six months later. It is possible that HIV-1 uninfected partners may be reluctant to discontinue PrEP, for example if they do not trust their partner’s motivation to consistently use ART or if the uninfected partner has additional sexual partners. We will explore the ability to discontinue PrEP.</div>\n<div>\n Through interviewer-administered questionnaires, we will assess couples’ attitudes and understanding of PrEP discontinuation.</div>\n
      • study_title<p>\n An open-label, pilot demonstration and evaluation project of antiretrovira-based HIV-1 prevention among high-risk HIV-1 serodiscordant African couples.</p>\n
      • laymans_summary(null)
      • short_titlePartners Demonstration Project
      • protocol_noECCT/12/08/01
      • version_no2.0
      • date_of_protocol10-07-2012
      • study_drugEmtricitabine 200mg/Tenofovir 300mg
      • disease_conditionHIV-1 Prevention
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameEmtricitabine 200mg/Tenofovir 300mg (Truvada®)
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressRwamba@csrtkenya.org
      • applicant_covering_letter1
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      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr. Kenneth Ngure
      • declaration_date119-09-2013
      • declaration_principal_investigatorDr. Nelly R.Mugo
      • declaration_date219-09-2013
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n <u>For Couples:</u></p>\n<ul>\n <li>\n Risk score defining higher HIV-1 risk</li>\n <li>\n Sexually active (defined as havind had vaginal intercourse at least  6 times in the previous three months)</li>\n <li>\n Willing to enter the study as a couple and intending to remain as a couple for the next 12 months.</li>\n</ul>\n<p>\n <u>For HIV-1 Uninfected members of the couple (Partner participants)</u></p>\n<ul>\n <li>\n Age <span style=\"color: rgb(0, 0, 0); font-family: Verdana, Tahoma, Arial, sans-serif; font-size: 13px; line-height: 17px; text-align: -webkit-center;\">≥ 18</span></li>\n <li>\n <span style=\"color: rgb(0, 0, 0); font-family: Verdana, Tahoma, Arial, sans-serif; font-size: 13px; line-height: 17px; text-align: -webkit-center;\">Able and willing to provide written informed consent</span></li>\n <li>\n <span style=\"color: rgb(0, 0, 0); font-family: Verdana, Tahoma, Arial, sans-serif; font-size: 13px; line-height: 17px; text-align: -webkit-center;\">HIV-1 Uni<span style=\"font-family:arial,helvetica,sans-serif;\">nfected based on negative HIV-1 rapid tests, both at study screening and at the enrollment visit</span></span></li>\n <li>\n <span style=\"color: rgb(0, 0, 0); font-family: Verdana, Tahoma, Arial, sans-serif; font-size: 13px; line-height: 17px; text-align: -webkit-center;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Adequate renal function, defined by normal creatinine levels and estimated creatinine clearance </span></span><span style=\"color: rgb(0, 0, 0); font-family: Verdana, Tahoma, Arial, sans-serif; font-size: 13px; line-height: 17px; text-align: -webkit-center;\">≥ 60 ml/min</span></li>\n</ul>\n<p>\n <u><span style=\"color: rgb(0, 0, 0); font-family: Verdana, Tahoma, Arial, sans-serif; font-size: 13px; line-height: 17px; text-align: -webkit-center;\">For HIV-1 Infected members of the couple (Index participants)</span></u></p>\n<ul>\n <li>\n <span style=\"color: rgb(0, 0, 0); font-family: Verdana, Tahoma, Arial, sans-serif; font-size: 13px; line-height: 17px; text-align: -webkit-center;\">Age </span><span style=\"color: rgb(0, 0, 0); font-family: Verdana, Tahoma, Arial, sans-serif; font-size: 13px; line-height: 17px; text-align: -webkit-center;\">≥ 18</span></li>\n <li>\n <span style=\"color: rgb(0, 0, 0); font-family: Verdana, Tahoma, Arial, sans-serif; font-size: 13px; line-height: 17px; text-align: -webkit-center;\">Able and willing to provide written informed consent</span></li>\n <li>\n HIV-1 Infected based on positive rapid HIV-1 tests, according to national algorithm</li>\n</ul>\n<p>\n Note: Current pregnancy and breastfeeding are premitted for HIV-1 infected partners.</p>\n
      • principal_exclusion_criteria<p>\n <u>For couples:</u></p>\n<ul>\n <li>\n Participated in the Partners PrEP Study</li>\n</ul>\n<p>\n <u>For HIV-1 Uninfected members of the couple (partner participants)</u></p>\n<ul>\n <li>\n Infected with hepatitis B virus, as determined by a negative hepatitis B surface antigen test .</li>\n <li>\n currently pregnant or breastfeeding</li>\n <li>\n cureently enrolled in an HIV-1 prevention clinical trial</li>\n <li>\n currently using PrPEP</li>\n <li>\n Enrollment of individuals with active and serious infections or active clinically significant medical problems will be at the discretion of the site investigator.</li>\n</ul>\n<p>\n <u>For HIV-1 infected members of the couple (Index participants)</u></p>\n<ul>\n <li>\n History of WHO stage 3 or 4 conditions</li>\n <li>\n currently on ART</li>\n <li>\n Currently enrolled in an HIV-1 treatment study</li>\n</ul>\n
      • primary_end_points<ol>\n <li>\n <strong>We will evaluate the ability to do targeted enrollment of higher-risk HIV-1 serodiscordant couples into a longitudinal HIV-1 prevention study</strong></li>\n</ol>\n<p>\n The primary outcomes of this aim will be the screened to eligible ratio of HIV-1 serodiscordant couples recruited for this open-label study, the proportion of eligible couples who decide to enroll in the cohort, and the costs of screening and targeting high-risk couples.</p>\n<ol start=\"2\">\n <li>\n <strong>We will assess user preferences among high-risk HIV-1 serodiscordant couples for ART initiation for HIV-1 infected partners and PrEP for HIV-1 uninfected partners.</strong></li>\n</ol>\n<p>\n The primary outcomes for this aim will be measured at baseline and quarterly through an interviewer-administered questionnaire. The questionnaire will specifically ask about willingness to use PrEP or ART for HIV-1 prevention and which method the participant would prefer. Reasons for the choice and concerns about both methods will also be collected through mixed-methods approaches.</p>\n<ol start=\"3\">\n <li>\n <strong>We will ascertain initiation of and adherence to PrEP among HIV-1 uninfected partners, when implemented as a bridge to ART.</strong></li>\n</ol>\n<p>\n The primary measures of adherence will be collection of PrEP, clinic-based pill counts of unused study pills as recorded at each follow-up visit, and MEMS cap data on how frequently the pill bottle was opened. Blood samples for detection and quantification of PrEP levels (testing in batch) will be done for those who seroconvert to HIV-1 and a subset who remain HIV-1 uninfected.</p>\n<ol start=\"4\">\n <li>\n <strong>We will ascertain initiation of and adherence to ART among HIV-1 infected partners.</strong></li>\n</ol>\n<p>\n The primary measures of ART adherence will be ART initiation at a local ART provider and plasma HIV-1 RNA levels taken every 6 months for HIV-1 infected partners.</p>\n<ol start=\"5\">\n <li>\n <strong>We will assess factors influencing preferences, uptake and adherence for antiretroviral-based HIV-1 prevention.</strong></li>\n</ol>\n<p>\n Through interviewer-administered questionnaires, correlates of preferences, uptake and adherence to ART and PrEP will be assessed, including characteristics of sexual risk (i.e., sexual frequency, condom use, whether the HIV-1 uninfected partner reports outside partners), depression and substance use, gender of the HIV-1 uninfected partner, fertility intentions, partnership characteristics (whether the couple is cohabiting, has children, is together throughout follow-up, whether members have other partners, and whether the HIV-1 infected partner initiates ART), and clinical characteristics of the HIV-1 infected partner (e.g., CD4 count, WHO stage).</p>\n<ol start=\"6\">\n <li>\n <strong>We will assess the feasibility of PrEP discontinuation in couples in which the HIV-1 infected partner initiates ART</strong></li>\n</ol>\n<p>\n Through interviewer-administered questionnaires, we will assess couples’ attitudes and understanding of PrEP discontinuation.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy1
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyEffectiveness of Truvada® for HIV prevention in real world settings
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyOpen label pilot demonstration and evaluation project
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \'Trebuchet MS\', Tahoma, Verdana, Arial, sans-serif; font-size: 13px; line-height: 20px;\">\n Thika partners in Prevention, Site has 32 full time clinical trial staff (including physicians, nurses, counsellors, pharmacists).</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \'Trebuchet MS\', Tahoma, Verdana, Arial, sans-serif; font-size: 13px; line-height: 20px;\">\n Principal Investigator: Dr. Nelly R. Mugo  MBCHB,MMED,MPH</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \'Trebuchet MS\', Tahoma, Verdana, Arial, sans-serif; font-size: 13px; line-height: 20px;\">\n Study coordinator: Dr. Kenneth Ngure  BSc,MPH,MSc,PhD</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \'Trebuchet MS\', Tahoma, Verdana, Arial, sans-serif; font-size: 13px; line-height: 20px;\">\n Lead Physician: Dr. Elizabeth Irungu  MBCHB, MPH</p>\n
      • other_details_explanation<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \'Trebuchet MS\', Tahoma, Verdana, Arial, sans-serif; font-size: 13px; line-height: 20px;\">\n Although the HIV-1 epidemic affects many populations  in Africa (commercial sex workers, high-risk men employed far from their stable homes, young sexually active individuals), majority of HIV-1 transmissions to adults in Africa occur  within stable, heterosexual, HIV-1 discordant couples. HIV-1 uninfected individuals within HIV-1  discordant partnerships are at high risk for HIV acquisition. HIV-1 discordant couples face unique challenges, including concerns over disclosure of HIV-1  status, HIV-1 associated stigma, and fear of domestic violence. In particular, issues regarding conception are especially concerning to HIV-1 discordant couples. Pregnancy rates in Africa are high (commonly 15-20 per 100 person-years), and social and familial pressures to seek pregnancy are strong, making HIV-1 transmission risk especially great for HIV-1  discordant couples, especially interventions that might allow pregnancy to occur safely, are urgently needed.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \'Trebuchet MS\', Tahoma, Verdana, Arial, sans-serif; font-size: 13px; line-height: 20px;\">\n In the absence of an HIV-1 cure and recognizing the long development timelines for microbicides and vaccines (that might have substantial impacts on the epidemic but are generally agreed to be over a decade away), other prevention strategies must be developed. </p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \'Trebuchet MS\', Tahoma, Verdana, Arial, sans-serif; font-size: 13px; line-height: 20px;\">\n Pre-exposure chemoprophylaxis, or PrEP, in which an HIV-1 uninfected individual at high risk for contracting HIV-1  takes antiretroviral medications to maintain  blood and genital drug levels sufficient to prevent HIV-1 acquisition, has been proposed as a novel potential HIV-1  prevention strategy. Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) has shown to be safe and effective medications to serve as PrEP. FTC/TDF is licenced , and had its label changed by FDA, for the treatment and prevention of HIV-1 infection. Truvada is potent , has long half-life (allowing once daily dosing) , achieve high concentrations in genital tract secretions, have high thresholds against development of viral resistance, do not interact with commonly used medications (e.g. hormonal contraceptives , anti tuberculsis medications), and has shown to be safe and well tolerated when used in HIV-1 prevention. </p>\n
      • other_details_regulatory_notapproved<p>\n None Pending</p>\n
      • other_details_regulatory_approved<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \'Trebuchet MS\', Tahoma, Verdana, Arial, sans-serif; font-size: 13px; line-height: 20px;\">\n 1.KNH/UON-ERC Approved 2 sites in Kenya (Thika and Kisumu)</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \'Trebuchet MS\', Tahoma, Verdana, Arial, sans-serif; font-size: 13px; line-height: 20px;\">\n 2.University of Washington IRB, approved 2 sites in Kenya (Thika and Kisumu)</p>\n
      • other_details_regulatory_rejected<p>\n NONE</p>\n
      • other_details_regulatory_halted
      • estimated_duration24 Months
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states2
      • number_of_sites2
      • multi_country_listKenya\nUganda
      • data_monitoring_committeeNo
      • total_enrolment_per_site500
      • total_participants_worldwide1000
      • 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_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenYes
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersYes
      • subjects_others_specifyHIV infected partners in HIV-1 discordant relationships
      • investigator1_given_nameDr. Jared
      • investigator1_middle_nameMurray
      • investigator1_family_nameBaeten
      • investigator1_qualificationMD,PhD
      • investigator1_professional_addressUniversity of Washington, Box 359927; 325 Ninth Avenue, Seattle Washington 98104
      • investigator1_telephone206 520 3808
      • investigator1_emailjbaeten@uw.edu
      • organisations_transferred_Yes
      • number_participants500
      • notification
      • approval_date01-10-2012
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted11-08-2013
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2018-08-28 16:19:41
      • created2013-09-19 16:16:00
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id148
        • application_id215
        • given_nameDr. Nelly
        • middle_nameRwamba
        • family_nameMugo
        • qualificationMBCHB, MMED, MPH
        • professional_address 19865-00202
        • telephone 067-22561, 0723914057
        • emailRwamba@csrtkenya.org
        • created2013-09-19 16:27:59
        • modified2013-09-20 11:56:55
    • SiteDetail(array)
      • 0(array)
        • id183
        • application_id215
        • county_id22
        • site_namePartners in Prevention, Thika Site
        • physical_addressOAU Road, Near Thika Nursing Home
        • contact_detailsP.O Box 19865-00202
        • contact_personDr. Kenneth Ngure
        • site_capacity(null)
        • misc(null)
        • created2013-09-19 16:27:59
        • modified2013-09-20 11:56:55
        • County(array)
          • id22
          • county_nameKiambu
          • created2012-06-15 10:24:37
          • modified2012-06-15 10:24:37
      • 1(array)
        • id184
        • application_id215
        • county_id42
        • site_namePartners in Prevention, Kisumu Site
        • physical_addressAgoi Street
        • contact_detailsP.O Box 614-40100
        • contact_personJosephine B. Odoyo
        • site_capacity(null)
        • misc(null)
        • created2013-09-19 17:11:17
        • modified2013-09-20 11:56:55
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id116
        • application_id215
        • sponsorUniversity of Washington
        • sponsor_type(null)
        • contact_personDr. Nelly R. Mugo
        • addressP.O Box 19865-00202
        • telephone_number06722561
        • fax_numberN/A
        • cell_number0733629665
        • email_addressRwamba@csrtkenya.org
        • created2013-09-19 16:27:59
        • modified2013-09-20 11:56:55
  • 2(array)
    • Application(array)
      • id21
      • user_id21
      • trial_status_id5
      • abstract_of_study<p style=\"margin-left:108.0pt;\">\n <u>DESIGN</u>                      A5278s/AMC 074 is designed to assess the direction and magnitude of pharmacokinetic (PK) interactions between the antiretroviral agents efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) and the Kaposi’s sarcoma (KS) chemotherapy agents etoposide (ET), vincristine (VCR), and pegylated liposomal doxorubicin (PLD).  This substudy will coenroll a subset of participants randomized on ACTG parent studies A5263 and A5264 for PK sampling on no more than two occasions.  Estimates of participant-specific PK parameters for the parent study agents, obtained by maximum a posteriori (MAP) Bayesian estimation, will be compared to historical control data (KS agents) or estimates obtained for participants on A5264 Arm 1A (antiretroviral agents).</p>\n<p style=\"margin-left:144.0pt;\">\n  </p>\n<p style=\"margin-left:108.0pt;\">\n <u>DURATION</u>                One or two day PK visit(s)</p>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<ul>\n <li>\n Participants in Arm 1A of A5264 who enter A5264 Step 2 (Arm 2A) may have two PK visits</li>\n</ul>\n<p style=\"margin-left:126.0pt;\">\n  </p>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<p style=\"margin-left:144.0pt;\">\n <u>SAMPLE SIZE</u>            A5263: 45 participants who complete the PK blood draw visit; 15 participants in each A5263 arm. Participants enrolled who do not complete the PK visit will be replaced.</p>\n<p style=\"margin-left:144.0pt;\">\n A5264: 60 participants who complete the PK blood draw; 30 participants in each A5264 arm. Participants enrolled who do not complete the PK visit will be replaced.</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <u>POPULATION</u>            HIV-1 infected men and women enrolled in A5263 or A5264</p>\n
      • study_title<p>\n <strong>A5278 - Pharmacology Substudies of A5263 and A5264</strong></p>\n
      • laymans_summary<p style=\"margin-left:36.0pt;\">\n A5278s/AMC 074 will investigate the potential for drug-drug interactions among agents used for the chemotherapy of KS when given with the ART regimen, EFV/TDF/FTC.  These investigations will occur as a <strong>substudy</strong> to the parent protocols A5263 and A5264.  In A5263, the primary question to be evaluated is whether KS chemotherapy with ET, BV, and PLD and ART with EFV/TDF/FTC given concomitantly affects the PK characteristics of each other when compared with historical controls (when examining the PK of KS agents) and PK parameters obtained from participants randomized on A5264 to Arm 1A (ARV agents). In A5264, the primary question of whether co administration of ET with EFV/TDF/FTC alters the PK of ET when compared with historical controls will be addressed as well.  Additionally, the question of whether the PK of EFV/TDF/FTC is altered in the presence of ET will be investigated in a direct comparison of participants who are randomized to receive initially only the ART regimen, or the ART regimen and ET. PK samples will be collected using a sparse sampling strategy at one specified study day when the participants are receiving concomitant therapy. PK data analysis strategies using nonlinear mixed effects modeling and Bayesian-estimation will be used to obtain estimates of individual and population PK parameters for statistical comparisons. To date, no PK evaluations of these KS and ART regimens have been performed. Therefore, this substudy will provide the first PK data for these agents when used in combination. </p>\n
      • short_titlePK Substudy of A5263 and A5264
      • protocol_noECCT/12/07/03
      • version_noVersion 1.0
      • date_of_protocol25-08-2010
      • study_drugco-formulated EFV/TDF/FTC vs ET, VCR and Paclitaxel
      • disease_conditionAIDS-KS (Kaposi’s sarcoma )
      • 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_nameEtoposide, Paclitaxel, Vincristine
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressaksudoi@hotmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum1
      • 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_checklist0
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantAllan K Sudoi
      • declaration_date122-02-2013
      • declaration_principal_investigatorAbraham M Siika, MBChB, MMed, Msc - Site Principal Investigator
      • declaration_date222-02-2013
      • placebo_presentNo
      • study_objectives<h2>\n Primary Objectives</h2>\n<p>\n  </p>\n<p style=\"margin-left:36.0pt;\">\n The overall objective of ACTG 5278s/AMC074 is to investigate the potential for drug-drug interactions among agents used for the chemotherapy of KS and co-formulated EFV/TDF/FTC. </p>\n<p>\n  </p>\n<p>\n To investigate the effects of the concomitant EFV/TDF/FTC antiretroviral regimen on ET, VCR, and <strong>PTX</strong> PK in A5263, and assess these concentrations relative to historical controls (which do not include CYP3A inducers such as EFV).</p>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n<p>\n To investigate the effects of the KS chemotherapy used in Arms A, B, and C of A5263 on the PK of EFV regimen and assess these concentrations relative to historical controls.</p>\n<p>\n  </p>\n<p>\n To investigate the effects of the concomitant EFV/TDF/FTC antiretroviral regimen on ET in A5264 Arm 1B, and assess these concentrations relative to historical controls.</p>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n<p>\n To investigate the effects of ET on the PK parameters of EFV, TDF, and FTC, by comparing PK parameters obtained in A5264 without ET (Arm 1A) versus with ET (Arm 1B).</p>\n<p>\n  </p>\n<h2>\n 1.2       Secondary Objectives</h2>\n<p>\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 1.2.1    To investigate exposure-response relationships between EFV, TDF, and FTC PK parameters and markers of response (including adverse reactions) to HIV and KS treatment, and to investigate exposure-response relationships between ET, VCR, and <strong>PTX</strong> PK parameters and markers of response (including adverse reactions) to KS treatment.</p>\n<p>\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 1.2.2    To compare the effects of the EFV/TDF/FTC antiretroviral regimen in<br />\n A5264 on ET PK when ET is initiated at the same time as EFV/TDF/FTC (Arm 1B) to ET PK when ET treatment is delayed (Arm 2A).</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 1.2.3    To investigate the effects of ET on EFV, TDF, and FTC PK through within-subject comparisons of EFV, TDF, and FTC  PK parameters, among participants randomized to A5264 Arm 1A who go on to provide PK samples on Arm 2A.</p>\n<p>\n  </p>\n<p>\n 1.2.4    To investigate the effects of the KS chemotherapy used in Arms A, B, and C of A5263 on the PK of TDF and FTC by comparing PK parameters obtained in A5263 Arms A, B and C with those obtained in A5264 Arm 1A.</p>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n This is found in section 4.0 of the protocol  under SELECTION AND ENROLLMENT OF PARTICIPANTS</p>\n<p>\n 4.1       Inclusion Criteria Step 1</p>\n<p style=\"margin-left:72.0pt;\">\n 4.1.1    Current enrollment in Arms 1A, 1B, or 1C of A5263 or Arms 1A or 1B of A5264.</p>\n<p style=\"margin-left:72.0pt;\">\n 4.1.2    Current use of EFV/TDF/FTC.</p>\n<p style=\"margin-left:72.0pt;\">\n 4.1.3    Ability and willingness of participant or legal guardian/representative to provide informed consent</p>\n<p>\n 4.2       Inclusion Criteria Step 2</p>\n<p style=\"margin-left:36.0pt;\">\n 4.2.1    Current enrollment in Step 2 of A5264.</p>\n<p style=\"margin-left:36.0pt;\">\n 4.2.2    Current use of EFV/TDF/FTC.</p>\n
      • principal_exclusion_criteria<p>\n The exclusion criteria of the parent studies will be applied. These will be attached separately to the application</p>\n
      • primary_end_points<p>\n The endpoints are located in section 9.2 of the protocol as follows:</p>\n<p>\n 9.2       Endpoints</p>\n<p>\n 9.2.1    Primary Endpoints</p>\n<p style=\"margin-left:115.2pt;\">\n 9.2.1.1    A5263 Chemotherapeutics</p>\n<p style=\"margin-left:115.2pt;\">\n <u>ET</u>: Subject-specific estimates of apparent oral clearance (CL/F) for ET obtained by applying maximum a posteriori (MAP) Bayesian estimation (as described in Section 10.2) to concentrations in plasma samples collected from participants randomized to Arm A of A5263, on day 6 (±1) of the first ET cycle, prior to and approximately 1 and 4h after the dose. </p>\n<p style=\"margin-left:115.2pt;\">\n <u>VCR:</u>  Subject-specific estimates of systemic clearance (CL) for VCR obtained by applying MAP Bayesian estimation (as described in Section 10.4) to concentrations in plasma samples collected from participants randomized to Arm B of A5263, on the BV dosing day (day 1) of the first or second BV cycle, prior to, at the end of, and 4h after the end of the IV infusion of BV (administered over a 3-5 min period).  (BLM is primarily eliminated by renal excretion.  BLM also undergoes hydrolysis by BLM hydrolase. Therefore, BLM is expected to neither alter nor be altered by concomitant EFV/TDF/FTC.)</p>\n<p style=\"margin-left:115.2pt;\">\n <u>PLD:</u>  Subject-specific estimates of C_max estimated as observed concentrations of PLD in plasma samples collected from participants randomized to Arm C of A5263, during the first or second PLD cycle, 5 minutes prior to the end of the PLD infusion (under the assumption that the maximum concentration occurs at this time).</p>\n<p style=\"margin-left:115.2pt;\">\n 9.2.1.2    A5263 ART</p>\n<p style=\"margin-left:115.2pt;\">\n For Arm A, estimated subject-specific EFV AUCs obtained by applying MAP Bayesian estimation (as described in Section 10.1) to concentrations in plasma samples collected from participants randomized to each of the 3 arms of A5263, on day 6 (±1) of the first ET cycle, approximately 12 h (within 10 and 20 h) after the EFV/TDF/FTC dose taken the evening before, and approximately 1 and 4 hours after the first blood draw for PK.  For Arms B and C, the day of PK sampling is the dosing day (day 1) of the first or second cycle of BV and PLD, respectively. (If PK visit is day 1 of the first cycle, participants must have taken EFC/TDF/FTC for at least 3 days prior to the PK visit.)</p>\n<p style=\"margin-left:115.2pt;\">\n 9.2.1.3    A5264 Chemotherapeutic</p>\n<p style=\"margin-left:115.2pt;\">\n Subject-specific estimates of ET CL/F obtained by applying MAP Bayesian estimation (as described in Section 10.2) to concentrations in plasma samples collected from participants randomized to Arm 1B of A5264, on day 6 (±1) of the first ET cycle, prior to and approximately 1 and 4 h after the first ET dose. </p>\n<ol>\n <li value=\"NaN\">\n A5264 ART</li>\n</ol>\n<p style=\"margin-left:115.2pt;\">\n Estimated subject-specific EFV, TDF and FTC AUCs obtained by applying MAP Bayesian estimation (as described in Section 10.1) to concentrations in plasma samples collected from participants of A5264, approximately 12 h (within 10 and 20 h) after the EFV/TDF/FTC dose taken the evening before, and approximately 1 and 4 h after the first blood draw for PK samples. For participants randomized to Arm 1A (delayed ET), PK samples will be collected on day 6 (±1) after the start of the ART regimen.  For participants randomized to Arm 1B (immediate ET) or enrolling in Arm 2A, PK samples will be collected on day 6 (±1) of the first ET cycle (and day 6 (±1) after the start of the ART regimen).</p>\n<p>\n 9.2.2    Secondary Endpoints</p>\n<p style=\"margin-left:115.2pt;\">\n 9.2.2.1    For participants on all arms of the two parent studies, subject-specific estimates of EFV, TDF, and FTC AUCs and plasma HIV-1 RNA and KS response markers at week 48.</p>\n<p style=\"margin-left:115.2pt;\">\n 9.2.2.2    Subject-specific estimates of ET CL/F obtained for participants on Arms 1B and 2A of A5264, as described in 9.2.1.3 above.</p>\n<p style=\"margin-left:115.2pt;\">\n 9.2.2.3    Subject-specific estimates of EFV AUC (as described in 9.2.1.2 above) and TDF and FTC AUCs (as described in 9.2.2.4 below) for participants on Arm 1A A5264 who also underwent PK sampling in A5264 Step 2 (Arm 2A).</p>\n<p style=\"margin-left:115.2pt;\">\n 9.2.2.4    Estimated subject-specific TDF and FTC AUC for participants on A5263 Arms A, B, and C as described in Section 10.1.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety0
      • scope_efficacy0
      • 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_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n Abraham M. Siika MBChB, MMed, MS- Site Leader/ Principal Investigator</p>\n<p>\n Naftali Busakhala - MBChB, MMed- Investigator</p>\n<p>\n Evangeline Njiru - MBChB, MMed- Investigator</p>\n<p>\n Charles Kwobah, MBChB- Medical Officer</p>\n<p>\n Mercy Karoney  MBChB- Medical Officer</p>\n<p>\n Simon Wachira Njuguna, B Pharm, MPSK - Pharmacist of Record</p>\n<p>\n Kipruto Kirwa, BSc, MPH, PhD- Quality Manager</p>\n<p>\n Priscilla Cheruiyot, BScN, MPH- Site Coordinator</p>\n<p>\n Martha Mokaya, BSc, MBA- Data Manager</p>\n<p>\n Wilson Lokitala Ekiru, BSc IT- Assistant Data Manager</p>\n<p>\n Agnes M. Nzioka, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Betty Meli, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Michael Tanui, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Julie Choge -  Recruitment Officer</p>\n<p>\n Dorothy Mwimali -  Recruitment Officer</p>\n<p>\n Cecilia Chebet, Dip Counselling - Recruitment Officer</p>\n<p>\n Beatrice Jakait, B Pharm- Back-up Pharmacist</p>\n<p>\n Zipporah Sambili, Dip Pharm- Back-up Pharmaceutical Technologist</p>\n<p>\n Chris Sande, KHRCN- Study Nurse</p>\n
      • other_details_explanation<p style=\"margin-left:14.2pt;\">\n This is a substudy of A5263 and A5264 studies which are conducted in Resource Limited Settings.</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n  Moi Teaching and Referral Hospital/Moi University Institutional Research and Ethics Committee (IREC). Approval date June 7, 2012. The approval is for MUCRC site only</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationOne or two day PK visit(s)
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • 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 (seven)
      • number_of_sites2
      • multi_country_listKenya\n\nMalawi\n\nSouth Africa\n\nUganda\n\nBrazil\n\nPeru\n\nZimbabwe
      • data_monitoring_committeeNo
      • total_enrolment_per_site15 participants at Eldoret. Information in other sites not immediately available
      • total_participants_worldwide105
      • 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_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameN/A
      • investigator1_middle_name
      • investigator1_family_nameN/A
      • investigator1_qualificationN/A
      • investigator1_professional_addressN/A
      • investigator1_telephoneN/A
      • investigator1_emailabrahamsiika@gmail.com
      • organisations_transferred_No
      • number_participants15 participants at the Eldoret Site
      • notification
      • approval_date25-08-2010
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted11-08-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2020-08-11 11:26:33
      • created2013-02-06 16:25:42
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id24
        • application_id21
        • given_nameAbraham
        • middle_nameMosigisi
        • family_nameSiika
        • qualificationMBChB, MMed, MSc
        • professional_addressP O Box, 4606-30100, Eldoret
        • telephone254721280785
        • emailambarahamsiika@gmail.com
        • created2013-02-20 16:30:08
        • modified2020-08-11 11:26:33
    • SiteDetail(array)
      • 0(array)
        • id35
        • application_id21
        • county_id27
        • site_nameMoi University Clinical Research Centre
        • physical_addressAMPATH at MTRH, Nandi Road, Eldoret
        • contact_details+254 53 2060850
        • contact_personAllan Sudoi
        • site_capacity(null)
        • misc(null)
        • created2013-02-20 16:30:08
        • modified2020-08-11 11:26:33
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
      • 1(array)
        • id36
        • application_id21
        • county_id35
        • site_nameKEMRI Walter Reed Project
        • physical_addressKericho District Hospital Grounds
        • contact_details0713603225
        • contact_personHellen Ngeno
        • site_capacity(null)
        • misc(null)
        • created2013-02-20 16:52:06
        • modified2020-08-11 11:26:33
        • County(array)
          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
    • Sponsor(array)
      • 0(array)
        • id18
        • application_id21
        • sponsorThe National Institute of Allergy and Infectious Diseases (NIAID) and The National Institute of Dental and Craniofacial Research (NIDCR)
        • sponsor_typeOthers
        • contact_person
        • address9000 Rockville Pike Bethesda, Maryland 20892
        • telephone_number301-496-4000
        • fax_number
        • cell_number301-496-4000
        • email_addressNIHinfo@od.nih.gov
        • created2013-02-20 16:30:08
        • modified2020-08-11 11:26:33
  • 3(array)
    • Application(array)
      • id172
      • user_id21
      • trial_status_id5
      • abstract_of_study<p style=\"margin-left:108.0pt;\">\n <u>DESIGN</u>                      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, Figure 1.</p>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<p style=\"margin-left:108.0pt;\">\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.</p>\n<p style=\"margin-left:108.0pt;\">\n                                    </p>\n<p style=\"margin-left:108.0pt;\">\n <u>Genotyping and Identification of Cohort and ARV Regimen </u></p>\n<p style=\"margin-left:108.0pt;\">\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. </p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:108.0pt;\">\n 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:</p>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<ol>\n <li>\n Selection of the appropriate cohort</li>\n</ol>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<p style=\"margin-left:108.0pt;\">\n AND</p>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<ol>\n <li value=\"2\">\n 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)</li>\n</ol>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<p style=\"margin-left:126.0pt;\">\n OR</p>\n<p style=\"margin-left:126.0pt;\">\n  </p>\n<p style=\"margin-left:126.0pt;\">\n Choice of at least two NRTIs if the potential participant is to be placed into Cohort B or Cohort C</p>\n<p style=\"margin-left:126.0pt;\">\n  </p>\n<p style=\"margin-left:126.0pt;\">\n OR</p>\n<p style=\"margin-left:126.0pt;\">\n  </p>\n<p style=\"margin-left:126.0pt;\">\n The proposed ARV regimen if the potential participant is to be placed into Cohort D.</p>\n<p>\n  </p>\n<p style=\"margin-left:108.0pt;\">\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 following cohorts, as outlined below.</p>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<p style=\"margin-left:108.0pt;\">\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.</p>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<p style=\"margin-left:108.0pt;\">\n 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.</p>\n<p>\n  </p>\n<p style=\"margin-left:108.0pt;\">\n <u>DURATION</u>                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.</p>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<p style=\"margin-left:108.0pt;\">\n <u>SAMPLE SIZE</u>            500 participants.</p>\n<p>\n  </p>\n<p style=\"margin-left:108.0pt;\">\n <u>POPULATION</u>            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.</p>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<p style=\"margin-left:108.0pt;\">\n <u>RANDOMIZATION</u>    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.</p>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<p style=\"margin-left:108.0pt;\">\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.</p>\n<p>\n  </p>\n<p style=\"margin-left:108.0pt;\">\n <u>REGIMEN</u>                  <u>Cohort Profiles and Proposed ARV Regimens (Steps 1 and 2)</u></p>\n<p>\n  </p>\n<p style=\"margin-left:108.0pt;\">\n Cohort A:  No resistance to NRTIs, PIs, or NNRTI</p>\n<ul>\n <li>\n Continue current second-line regimen; NRTIs can be modified</li>\n</ul>\n<p style=\"margin-left:90.0pt;\">\n  </p>\n<p style=\"margin-left:108.0pt;\">\n Cohort B:  Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs)</p>\n<p>\n  </p>\n<p style=\"margin-left:108.0pt;\">\n Participants without active hepatitis B infection at screening will be randomized 1:1 to sub-cohort B1 or B2</p>\n<ul>\n <li>\n Sub-cohort B1: Best available NRTIs, RAL, and DRV/RTV</li>\n</ul>\n<ul>\n <li>\n Sub-cohort B2: ETR, RAL, and DRV/RTV</li>\n</ul>\n<p style=\"margin-left:108.0pt;\">\n Participants with active hepatitis B infection at screening will be assigned to:</p>\n<ul>\n <li>\n Sub-cohort B3: RAL, DRV/RTV, and FTC/TDF or TDF plus 3TC</li>\n</ul>\n<p>\n  </p>\n<p style=\"margin-left:108.0pt;\">\n Cohort C:  Resistance to NRTIs and ETR or resistance to ETR alone (and may have resistance to PIs other than DRV)</p>\n<ul>\n <li>\n Best available NRTIs, RAL, and DRV/RTV</li>\n</ul>\n<p style=\"margin-left:126.0pt;\">\n  </p>\n<p style=\"margin-left:108.0pt;\">\n Cohort D:  Multiple NRTI resistance and/or DRV/RTV resistance or prior RAL exposure</p>\n<ul>\n <li>\n Best available regimen, including study-provided and any locally available drugs</li>\n</ul>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<p style=\"margin-left:108.0pt;\">\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 as specified in section 5.3.1.  Refer to section 5.0 for additional details.</p>\n
      • study_title<p>\n <strong>A</strong><strong>5288 "Management Using the Latest Technologies in Resource-limited Settings to Optimize Combination Therapy After Viral Failure" (MULTI-OCTAVE)</strong></p>\n
      • laymans_summary(null)
      • short_titleMULTI-OCTAVE (Management Using Latest Technologies to Optimize Combination Therapy After Viral Failure)
      • protocol_noECCT/12/07/01
      • version_no1.0
      • date_of_protocol16-09-2011
      • study_drugDarunavir (Prezista),Etravirine (Intelence),Raltegravir (Isentress),Ritonavir (Norvir), Rifabutin (Mycobutin), Emtricitabine/Tenofovir Disoproxil Fumarate (Truvada)
      • disease_conditionThird Line HIV Therapy
      • 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_nameAs above
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressaksudoi@hotmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantAllan K Sudoi
      • declaration_date122-07-2013
      • declaration_principal_investigatorAbraham M Siika, MBChB, MMed, Msc - Site Principal Investigator
      • declaration_date222-07-2013
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<h2>\n 4.1       Inclusion Criteria for Step 1</h2>\n<p style=\"margin-left: 40px;\">\n 4.1.1    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: 40px;\">\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: 40px;\">\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 style=\"margin-left: 40px;\">\n 4.1.2    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: 40px;\">\n             NOTE: All potential participants with prior RAL exposure will be assigned to Cohort D.</p>\n<p style=\"margin-left: 40px;\">\n 4.1.3    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: 40px;\">\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: 40px;\">\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 style=\"margin-left: 40px;\">\n 4.1.4    Confirmation of VF of current second-line PI-based ART.</p>\n<p style=\"margin-left: 40px;\">\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: 40px;\">\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: 40px;\">\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 style=\"margin-left: 40px;\">\n 4.1.5    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 style=\"margin-left: 40px;\">\n 4.1.6    Laboratory values obtained within 30 days prior to study entry:</p>\n<ul style=\"margin-left: 40px;\">\n <li>\n Absolute neutrophil count (ANC) ≥ 500/mm³</li>\n <li>\n Hemoglobin ≥ 7.5 g/dL</li>\n <li>\n Platelet count ≥ 40,000/mm³</li>\n <li>\n Creatinine ≤ 2 X upper limit of normal (ULN)</li>\n <li>\n Aspartate aminotransferase (AST), serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT), serum glutamic pyruvic transaminase (SGPT), and alkaline phosphatase ≤ 5 x ULN</li>\n <li>\n Total bilirubin ≤ 2.5 x ULN</li>\n</ul>\n<p style=\"margin-left:90.0pt;\">\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<ul style=\"margin-left: 40px;\">\n <li>\n Creatinine clearance (CrCl) <u>></u>60 mL/min, either measured or estimated by Cockcroft-Gault equation  </li>\n</ul>\n<p style=\"margin-left:90.0pt;\">\n NOTE: A calculator for estimating the CrCl can be found at <u>www.fstrf.org/ACTG/ccc.html</u></p>\n<ul style=\"margin-left: 40px;\">\n <li>\n Hepatitis B panel that includes HbsAB, HBcAB, and HBsAG or only HBsAG, with plasma stored for later anti-HBs and anti-HBc.</li>\n</ul>\n<p style=\"margin-left:90.0pt;\">\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 style=\"margin-left: 40px;\">\n 4.1.7    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: 40px;\">\n 4.1.8    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:108.0pt;\">\n Acceptable forms of contraceptives include:</p>\n<ul style=\"margin-left: 80px;\">\n <li>\n Condoms (male or female) with or without a spermicidal agent</li>\n <li>\n Diaphragm or cervical cap with spermicide\n <ul>\n <li>\n Intrauterine device (IUD)</li>\n </ul>\n </li>\n <li>\n Hormonal contraception</li>\n</ul>\n<p style=\"margin-left:72.0pt;\">\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 style=\"margin-left:72.0pt;\">\n NOTE: Acceptable documentation of lack of reproductive potential is oral or written documentation from the participant.</p>\n<p style=\"margin-left: 40px;\">\n 4.1.9    Karnofsky performance score ³70 within 30 days prior to study entry.</p>\n<p style=\"margin-left: 40px;\">\n 4.1.10  Men and women aged ³18 years.</p>\n<p style=\"margin-left: 40px;\">\n 4.1.11  Ability and willingness of potential participant to provide informed consent.</p>\n<p style=\"margin-left: 40px;\">\n 4.1.12  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 style=\"margin-left: 40px;\">\n 4.1.13  Ability to take oral study medications.</p>\n<p style=\"margin-left: 40px;\">\n 4.1.14  No intention of permanent relocation that would preclude attending Step 1 and 2 study follow-up visits.</p>\n<p style=\"margin-left: 40px;\">\n 4.1.15  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:72.0pt;\">\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: 40px;\">\n 4.1.16  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:72.0pt;\">\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<h2>\n 4.3       Inclusion Criteria for Step 2</h2>\n<p style=\"margin-left: 40px;\">\n 4.3.1    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: 40px;\">\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 style=\"margin-left: 40px;\">\n 4.3.2    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: 40px;\">\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: 40px;\">\n 4.3.3    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: 40px;\">\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 style=\"margin-left:36.0pt;\">\n 4.3.4    Laboratory values obtained within 56 days prior to Step 2 entry:</p>\n<ul style=\"margin-left: 80px;\">\n <li>\n ANC ≥ 500/mm³</li>\n <li>\n Hemoglobin ≥ 7.5 g/dL</li>\n <li>\n Platelet count ≥ 40,000/mm³</li>\n <li>\n Creatinine ≤ 2 X ULN)</li>\n <li>\n AST, SGOT, ALT, SGPT, and alkaline phosphatase ≤ 5 x ULN</li>\n <li>\n Total bilirubin ≤ 2.5 x ULN</li>\n</ul>\n<p style=\"margin-left:90.0pt;\">\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<ul>\n <li>\n Creatinine clearance (CrCl) <u>></u>60 mL/min, either measured or estimated by Cockcroft-Gault equation</li>\n</ul>\n<p style=\"margin-left:90.0pt;\">\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: 40px;\">\n 4.3.5    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 style=\"margin-left: 40px;\">\n 4.3.6    Ability to continue to take oral study medications.</p>\n<p style=\"margin-left: 40px;\">\n 4.3.7    No intention of permanent relocation during Step 2 that would preclude attending study follow-up visits.</p>\n<p style=\"margin-left: 40px;\">\n 4.3.8    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<h2>\n 4.5       Inclusion Criteria for Step 3</h2>\n<p style=\"margin-left:72.0pt;\">\n 4.5.1    Current receipt of study-provided RAL, ETR, or DRV.</p>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n
      • principal_exclusion_criteria<h2>\n 4.2       Exclusion Criteria for Step 1</h2>\n<p style=\"margin-left: 40px;\">\n 4.2.1    Pregnancy or breast-feeding.</p>\n<p style=\"margin-left: 40px;\">\n 4.2.2    Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.</p>\n<p style=\"margin-left: 40px;\">\n 4.2.3    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: 40px;\">\n 4.2.4    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 style=\"margin-left: 40px;\">\n 4.2.5    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: 40px;\">\n 4.2.6    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 style=\"margin-left: 40px;\">\n 4.2.7    Active tuberculosis (TB) or rifampin exposure less than 2 weeks prior to study entry.</p>\n<h2>\n 4.4       Exclusion Criteria for Step 2</h2>\n<p style=\"margin-left:72.0pt;\">\n 4.4.1    Contraindication to the proposed Step 2 ARV regimen as determined by the site investigator.</p>\n<h2>\n 4.6       Exclusion Criteria for Step 3</h2>\n<p style=\"margin-left:72.0pt;\">\n 4.6.1    Indication for discontinuation of RAL, ETR, or DRV.</p>\n
      • primary_end_points<p>\n Suppression of plasma HIV-1 RNA to ≤200 copies/mL at 48 weeks.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n Abraham M. Siika MBChB, MMed, MS- Site Leader/ Principal Investigator</p>\n<p>\n Beatrice Wangari Ndege- Co-investigator</p>\n<p>\n Priscilla Cheruiyot, BScN, MPH- Site Coordinator</p>\n<p>\n Charles Kwobah, MBChB- Medical Officer</p>\n<p>\n Mercy Karoney  MBChB- Medical Officer</p>\n<p>\n Simon Wachira Njuguna, B Pharm, MPSK - Pharmacist of Record</p>\n<p>\n Kipruto Kirwa, BSc, MPH, PhD- Quality Manager</p>\n<p>\n Martha Mokaya, BSc, MBA- Data Manager</p>\n<p>\n Wilson Lokitala Ekiru, BSc IT- Assistant Data Manager</p>\n<p>\n Agnes M. Nzioka, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Betty Meli, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Michael Tanui, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Julie Choge -  Recruitment Officer</p>\n<p>\n Amina Msuo Shali - Recruitment Officer</p>\n<p>\n Dorothy Mwimali -  Recruitment Officer</p>\n<p>\n Cecilia Chebet, Dip Counselling - Recruitment Officer</p>\n<p>\n Beatrice Jakait, B Pharm- Back-up Pharmacist</p>\n<p>\n Chris Sande, KHRCN- Study Nurse</p>\n
      • other_details_explanation<p style=\"margin-left:36.0pt;\">\n This study will be conducted in RLS, including Kenya, to establish a SOC for management of persons thought to be failing second-line ARV regimens according to local definitions of ART-failure. Contemporary management tools of genotypic resistance testing and VL monitoring will be used to define appropriate third-line regimens for groups of patients and to monitor outcomes. The data generated by this study will be critical in the development of third-line management in these settings. In addition to providing data about clinical outcomes, this approach will provide information about the cost-effectiveness of these strategies.</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n Moi Teaching and Referral Hospital/Moi University Institutional Research and Ethics Committee (IREC). Approval granted on 9 May 2012 and continuing approval granted on May 9 2013.</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration48 weeks after registration/randomization of the last participant
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaMoi University Clinical Research Centre
      • single_site_physical_addressAMPATH at MTRH, Nandi Road
      • single_site_contact_personAllan Sudoi
      • single_site_telephone+254721821242
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states11
      • number_of_sites
      • multi_country_listKenya, India, Peru, South Africa, Thailand, Malawi, Haiti, Botswana, Brazil, Uganda, Zambia
      • data_monitoring_committeeYes
      • total_enrolment_per_site60 at Eldoret site.
      • 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_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameN/A
      • investigator1_middle_name
      • investigator1_family_nameN/A
      • investigator1_qualificationN/A
      • investigator1_professional_addressN/A
      • investigator1_telephoneN/An
      • investigator1_emailamsiika@africaonline.co.ke
      • organisations_transferred_No
      • number_participants60
      • notification
      • approval_date16-09-2011
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted22-07-2013
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2019-01-28 08:41:18
      • created2013-07-19 09:56:30
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id112
        • application_id172
        • given_nameAbraham
        • middle_nameMosigisi
        • family_nameSiika
        • qualificationMBChB, MMed, MSc
        • professional_addressP O Box, 4606-30100, Eldoret
        • telephone0721280785
        • emailamsiika@africaonline.co.ke
        • created2013-07-19 10:08:46
        • modified2013-07-22 15:39:05
    • SiteDetail(array)
      • 0(array)
        • id141
        • application_id172
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2013-07-19 10:08:46
        • modified2013-07-22 15:39:05
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id88
        • application_id172
        • sponsorNational Institutes of Health
        • sponsor_type(null)
        • contact_personBeatriz Grinsztejn, MD, PhD
        • addressAvenida Brasil 4365, Manguinhos Rio de Janeiro 21045--900 BRAZIL
        • telephone_number55 21 2270 7064
        • fax_number55 21 2564 4933
        • cell_number55 21 2270 7064
        • email_addressgbeatriz@ipec.fiocruz.br
        • created2013-07-19 10:08:46
        • modified2013-07-22 15:39:05
  • 4(array)
    • Application(array)
      • id134
      • user_id21
      • trial_status_id5
      • abstract_of_study<p style=\"margin-left: 108pt;\">\n <u>DESIGN</u>                      A5273 is a phase III, dual-arm, open-label, randomized, non-inferiority study for participants who are on a failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing first-line regimen. The study will evaluate the difference in virologic failure rate between two treatment arms: lopinavir/ritonavir plus raltegravir (LPV/r + RAL) and LPV/r plus best available nucleos(t)ide reverse transcriptase inhibitors (NRTIs).The NRTIs to be used will be specified by the site prior to randomization.</p>\n<p style=\"margin-left: 108pt;\">\n NOTE: On-study virologic failure is defined as confirmed viral load >400 copies/mL at or after week 24.</p>\n<p>\n  </p>\n<p style=\"margin-left: 160px;\">\n <u>DURATION</u>                Each participant will be followed for 96 weeks after enrollment.</p>\n<p style=\"margin-left: 160px;\">\n <u>SAMPLE SIZE</u>            600 (300 per study arm)</p>\n<p>\n  </p>\n<p style=\"margin-left: 108pt;\">\n <u>POPULATION</u>            Human immunodeficiency virus (HIV)-1 infected adults (age ≥18 years) who have confirmed virologic failure on an NNRTI-containing first-line regimen.</p>\n<p style=\"margin-left: 108pt;\">\n <u>STRATIFICATION</u>     Participants will be stratified by screening HIV-1 RNA (≥100,000 versus <100,000 copies/mL), screening CD4+ cell count (≥100 versus <100 cells/mm³), and selection of ZDV in the NRTI regimen (yes/no). Randomization will be balanced by site.</p>\n<p style=\"margin-left: 108pt;\">\n  </p>\n<p style=\"margin-left: 108pt;\">\n <u>REGIMEN</u>: At entry, all participants will stop the failing NNRTI-based regimen and switch to one of the following arms, randomly assigned in a 1:1 ratio:</p>\n<p style=\"margin-left: 144pt;\">\n Arm A: LPV/r plus RAL</p>\n<p style=\"margin-left: 144pt;\">\n Arm B: LPV/r plus best available NRTIs</p>\n<p style=\"margin-left: 108pt;\">\n Best available NRTI combinations will be selected by the site investigator prior to randomization from a list of combinations approved by the study or in consultation with the A5273 Clinical Management Committee (CMC). The NRTIs provided by the study are emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), abacavir/lamivudine/zidovudine (ABC/3TC/ZDV), abacavir/lamivudine (ABC/3TC), lamivudine/zidovudine (3TC/ZDV), abacavir (ABC), lamivudine (3TC), and zidovudine (ZDV).</p>\n
      • study_title<p>\n A5273: Multicenter Study of Options for SEcond-Line Effective Combination Therapy (SELECT)</p>\n
      • laymans_summary(null)
      • short_titleSELECT (SEcond-Line Effective Combination Therapy)
      • protocol_noECCT/12/04/03
      • version_no1.0
      • date_of_protocol22-11-2010
      • study_drugLPV/r plus RAL
      • disease_conditionSecond line HIV treatment
      • 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_nameISENTRESS and Lopinavir/Ritonavir
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressaksudoi@hotmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantAllan K Sudoi
      • declaration_date122-05-2013
      • declaration_principal_investigatorAbraham M Siika, MBChB, MMed, Msc - Site Principal Investigator
      • declaration_date222-05-2013
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n Section 4.1 of the protocol</p>\n<h2>\n 4.1       Inclusion Criteria</h2>\n<p style=\"margin-left:72.0pt;\">\n 4.1.1    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 viral load.</p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: For sites located in countries other than the United States, the term “licensed” refers to a kit that has been certified or licensed by an oversight body within that country and validated internally.</p>\n<p style=\"margin-left:72.0pt;\">\n WHO and CDC (U.S. 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 (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.</p>\n<p style=\"margin-left:72.0pt;\">\n 4.1.2    Confirmation of first-line virologic failure</p>\n<p style=\"margin-left:72.0pt;\">\n Failure of the first-line regimen is defined as two consecutive measurements of plasma HIV-1 RNA ≥1,000 copies/mL obtained at least one week apart while on an initial NNRTI-based regimen. The first measurement of plasma HIV-1 RNA ≥1,000 copies/mL must be obtained after at least 24 weeks of a NNRTI-based regimen. The first value can be obtained from medical records up to 90 days prior to study entry regardless of the laboratory that performed the test. The second measurement must be obtained within 45 days prior to study entry and performed in any DAIDS-approved laboratory. For potential study candidates in whom failure of first NNRTI-based regimen is suspected based on clinical and/or immunological criteria only or in the event that there is no measurement available within the 90-day period, site investigators can obtain both HIV-1 RNA measurements as part of A5273 screening procedures (samples must be obtained at least 7 days apart).</p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: If there were within-class drug substitutions in the initial regimen because of intolerance to one or more drugs, the participant is still considered to be on an initial regimen and is eligible for the protocol if he/she meets the other eligibility requirements.   </p>\n<p style=\"margin-left:72.0pt;\">\n 4.1.3    Laboratory values obtained within 45 days prior to study entry</p>\n<ul>\n <li>\n Absolute neutrophil count (ANC) >500/mm³</li>\n <li>\n Hemoglobin >8.5 g/dL</li>\n <li>\n Platelet count >50,000/mm³</li>\n <li>\n AST, serum glutamic oxaloacetic transaminase (SGOT), ALT, serum glutamic pyruvic transaminase (SGPT), and alkaline phosphatase <u><</u>5 x ULN</li>\n <li>\n Total bilirubin <u><</u>2.5 x ULN</li>\n <li>\n Calculated creatinine clearance (CrCl) <u>></u>60 mL/min, as estimated by the Cockroft-Gault equation (see section 6.3.9 for CrCl instructions).</li>\n</ul>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Investigators should refer to section 5.1.1 for additional guidance for those participants who are considering the use of a ZDV-containing regimen.</p>\n<p style=\"margin-left:72.0pt;\">\n 4.1.4    Females of reproductive potential (girls who have reached menarche, women who have not been post-menopausal for at least 24 consecutive months, (i.e., 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 entry.</p>\n<p style=\"margin-left:72.0pt;\">\n 4.1.5    Participants must refrain from participating in a conception process (i.e., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) and, if participating in sexual activity that could lead to pregnancy, the participant/partner must use at least one type of contraceptive.  All female participants must continue to use contraceptives for 12 weeks after stopping study medications.</p>\n<p style=\"margin-left:72.0pt;\">\n Acceptable types of contraceptives:</p>\n<ul>\n <li>\n Condoms (male or female) with or without spermicidal agent</li>\n <li>\n Diaphragm or cervical cap with spermicide</li>\n <li>\n Intrauterine device (IUD)</li>\n <li>\n Birth control drugs given by pills, shots, or placed on or under the skin</li>\n <li>\n NuvaRing</li>\n</ul>\n<p style=\"margin-left:72.0pt;\">\n Participants who are not of reproductive potential (girls who have not reached menarche, women who have been post-menopausal for at least 24 consecutive months, women who have undergone hysterectomy or bilateral salpingectomy or bilateral oophorectomy or tubal ligation, or men who have documented azoospermia) are not required to use contraceptives.  However, use of barrier methods of contraception is strongly encouraged to reduce the risk of HIV transmission during sexual contact.</p>\n<p style=\"margin-left:72.0pt;\">\n Acceptable documentation of sterilization is written or oral documentation communicated by clinician or clinician’s staff of one of the following:</p>\n<ul>\n <li>\n Physician report/letter</li>\n <li>\n Operative report or other source documentation in the participant record</li>\n <li>\n Discharge summary</li>\n <li>\n Laboratory report of azoospermia</li>\n <li>\n Follicle stimulating hormone (FSH) measurement elevated into the</li>\n</ul>\n<p style=\"margin-left:90.0pt;\">\n menopausal range as established by the reporting laboratory</p>\n<p style=\"margin-left:72.0pt;\">\n 4.1.6    Karnofsky performance score ³70 within 45 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n 4.1.7    Men and women age <u>></u>18 years.</p>\n<p style=\"margin-left:72.0pt;\">\n 4.1.8    Ability and willingness of participant or legal guardian/representative to provide informed consent.</p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Illiterate participants or participants with cognitive disabilities may be enrolled based on local regulatory policies, with the appropriate provisions for informed consent.</p>\n<p style=\"margin-left:72.0pt;\">\n 4.1.9    No intention to relocate away from current geographical area of residence for the duration of study participation.</p>\n
      • principal_exclusion_criteria<p>\n Section 4.2 of the protocol</p>\n<h2>\n 4.2       Exclusion Criteria</h2>\n<ol>\n <li value=\"NaN\">\n Use of any immunomodulator, HIV vaccine, or other investigational therapy within 45 days prior to study entry, with the exception of a tapering course of corticosteroids as acute therapy for pneumocystis jiroveci pneumonia (PCP) or acute asthma/chronic obstructive pulmonary disease flare and/or prednisone at a daily dose of <u><</u>10 mg (physiologic replacement dose).</li>\n <li value=\"NaN\">\n If the potential participant has had resistance testing, evidence of broad NRTI cross-resistance that, in the opinion of the investigator, would not allow selection of an effective NRTI combination if the participant were randomized to the LPV/r + best available NRTIs arm.</li>\n</ol>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Resistance testing is not required for study participation.</p>\n<ol start=\"3\">\n <li>\n Prior exposure to a PI.</li>\n <li value=\"NaN\">\n Known history of congenital long QT syndrome, hypokalemia, or planned use of other drugs that prolong the QT interval.</li>\n <li value=\"NaN\">\n Pregnancy or breast-feeding.</li>\n <li value=\"NaN\">\n Known history of chronic HBV infection or current HBV infection defined by the presence of hepatitis B surface antigen in serum or plasma.</li>\n <li value=\"NaN\">\n Active tuberculosis (TB) requiring treatment with rifampicin.</li>\n <li value=\"NaN\">\n Previously diagnosed malignancies other than basal cell carcinoma and cutaneous Kaposi sarcoma.</li>\n</ol>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Women with precancerous cervical lesions are not excluded from this protocol. If the lesions progress and the participant becomes too ill to participate, clinicians may choose to terminate the woman’s participation in the study.</p>\n<ol start=\"9\">\n <li>\n Requirement for taking any medications that are prohibited with the study drugs (see section 5.4).</li>\n <li value=\"NaN\">\n Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.</li>\n <li value=\"NaN\">\n Active drug or alcohol use or dependence or other condition that, in the opinion of the site investigator, would interfere with adherence to study requirements.</li>\n <li value=\"NaN\">\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.</li>\n</ol>\n
      • primary_end_points<p>\n Section 9.2.1 of protocol</p>\n<p>\n 9.2.1   Primary Endpoint</p>\n<p style=\"margin-left:72.0pt;\">\n The primary endpoint is time to virologic failure. Virologic failure is defined as confirmed viral load >400 copies/mL at or after week 24. </p>\n<p style=\"margin-left:72.0pt;\">\n Notes:</p>\n<ol>\n <li>\n Time to virologic failure will be defined as the time from randomization to the first of two consecutive HIV-1 RNA samples defining virologic failure.</li>\n <li>\n Confirmation will be determined based on any two consecutive evaluations meeting the virologic failure criterion regardless of the time between them.</li>\n <li>\n Participants discontinuing the study (for any reason, including death and end of study) will be handled as follows:\n <ol style=\"list-style-type:lower-alpha;\">\n <li>\n Participants with a final HIV-1 RNA evaluation at week 4 that is >400 copies/mL and <0.5 log₁₀lower than baseline will be considered a virologic failure at week 4.</li>\n <li>\n Participants with a final HIV-1 RNA evaluation at week 12 that is >400 copies/mL and <1 log₁₀ lower than baseline will be considered a virologic failure at week 12.</li>\n <li>\n Participants with an unconfirmed virologic failure (HIV-1 RNA >400 copies/mL) at or after week 24 will be considered as virologic failure as the study visit week of the unconfirmed value.</li>\n <li>\n All remaining participants will have their time to virologic failure censored at the study week of the last measured plasma HIV-1 RNA sample.</li>\n </ol>\n </li>\n</ol>\n
      • scope_diagnosis1
      • scope_prophylaxis1
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
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      • trial_human_pharmacology0
      • trial_administration_humans0
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      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Abraham M. Siika MBChB, MMed, MS- Site Leader/ Principal Investigator</p>\n<p>\n Faraj Some- MBChB, MSc- Investigator</p>\n<p>\n Charles Kwobah, MBChB- Medical Officer</p>\n<p>\n Mercy Karoney MBChB- Medical Officer</p>\n<p>\n Simon Wachira Njuguna, B Pharm, MPSK - Pharmacist of Record</p>\n<p>\n Kipruto Kirwa, BSc, MPH, PhD- Quality Manager</p>\n<p>\n Priscilla Cheruiyot, BScN, MPH- Site Coordinator</p>\n<p>\n Martha Mokaya, BSc, MBA- Data Manager</p>\n<p>\n Wilson Lokitala Ekiru, BSc IT- Assistant Data Manager</p>\n<p>\n Agnes M. Nzioka, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Betty Meli, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Michael Tanui, Dip Clin Med- Research Clinical Officer</p>\n<p>\n Julie Choge - Recruitment Officer</p>\n<p>\n Amina Msuo Shali- Recruitment Officer</p>\n<p>\n Dorothy Mwimali - Recruitment Officer</p>\n<p>\n Cecilia Chebet, Dip Counselling - Recruitment Officer</p>\n<p>\n Beatrice Jakait, B Pharm- Back-up Pharmacist</p>\n<p>\n Zipporah Sambili, Dip Pharm- Back-up Pharmaceutical Technologist</p>\n<p>\n Chris Sande, KHRCN- Study Nurse</p>\n
      • other_details_explanation<p style=\"margin-left:36.0pt;\">\n A5273 is intended to provide information that is applicable to the vast majority of RLS where resistance testing is not used routinely for selection of second-line regimens and PIs not needing refrigeration are preferred.</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n Moi Teaching and Referral Hospital/Moi University Institutional Research and Ethics Committee (IREC). Continuing Approval granted on March Approved on March 27,2013for Eldoret site only.</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationEach participant will be followed for 96 weeks after enrollment.
      • 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_comparatorLPV/r plus RAL
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaMoi University Clinical Research Centre
      • single_site_physical_address(null)
      • single_site_contact_person(null)
      • single_site_telephone(null)
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_statesTen (10)
      • number_of_sites
      • multi_country_listKenya, India, Peru, South Africa, Thailand, Malawi, Haiti, Brazil, Tanzania, Zimbabwe
      • data_monitoring_committeeYes
      • total_enrolment_per_site100 at Eldoret Site
      • total_participants_worldwide600
      • 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_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
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      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
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      • subjects_others_specify
      • investigator1_given_nameN/A
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      • investigator1_professional_addressN/A
      • investigator1_telephoneN/A
      • investigator1_emailamsiika@africaonline.co.ke
      • organisations_transferred_No
      • number_participantsUnknown
      • notification
      • approval_date22-11-2010
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted22-05-2013
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      • initial_date_submitted(null)
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      • final_date(null)
      • modified2018-12-07 10:57:19
      • created2013-05-22 09:33:46
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
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        • id83
        • application_id134
        • given_nameAbraham
        • middle_nameMosigisi
        • family_nameSiika
        • qualificationMBChB, MMed, MSc
        • professional_addressP O Box, 4606-30100, Eldoret
        • telephone0721280785
        • emailamsiika@africaonline.co.ke
        • created2013-05-22 09:41:11
        • modified2013-05-22 15:57:16
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        • county_id27
        • site_name
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        • misc(null)
        • created2013-05-22 09:41:11
        • modified2013-05-22 15:57:16
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
    • Sponsor(array)
      • 0(array)
        • id64
        • application_id134
        • sponsorThe National Institute of Allergy and Infectious Diseases
        • sponsor_type(null)
        • contact_personAnn Collier, MD
        • addressUniversity of Washington Harborview Medical Center, Box 359929 325 9th Avenue Seattle, WA 98104
        • telephone_number(206) 744-3293
        • fax_number(206) 744-3483
        • cell_number(206) 744-3293
        • email_addressacollier@u.washington.edu
        • created2013-05-22 09:41:11
        • modified2013-05-22 15:57:16
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