Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202108805211718 Date of Approval: 24/08/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Kuwa Free! - Live Free!
Official scientific title Co-benefits of Co-delivery of Long-acting Antiretrovirals and Contraceptives
Brief summary describing the background and objectives of the trial Long-acting (LA) antiretroviral therapy (ART), such as injectable cabotegravir and rilpivirine, has been receiving global clinical approvals and has the potential to address these barriers and improve patient adherence and persistence to treatment. LA ART regimens can potentially also increase options for patients and providers to individualize treatment plans, provide a powerful treatment option for those experiencing adherence issues related oral treatment options, and may ease the burden of health systems in RLS. Another major threat to AGYW’s health is unintended pregnancies and AGYWLHIV also face unique challenges in uptake and continuation of LA contraceptives. Use of LA ART may foster synergy in usage of LA contraceptives among AGYWLHIV. Study Aims Aim 1: To collect foundational data to better inform design of an effectiveness implementation trial. Aim 1a: To determine if combined cabotegravir/rilpivirine injectable use has bidirectional drug-drug interactions with injectable (depot medroxyprogesterone acetate [DMPA]) or implantable (etonogestrel or levonorgestrel) contraceptives. Aim 1b: To qualitatively explore points of convergence and divergence, preferences and values, and health systems readiness around wider-scale codelivery of LA ART and contraceptives. Aim 2: To evaluate the impact of clinic-provided, co-delivery of LA ART and contraceptives among AGYWLHIV. Aim 2a: To evaluate the impact on effectiveness outcomes of HIV treatment (viral suppression and adherence/persistence) and contraception (uptake and continuation rates). Aim 2b: To evaluate the impact on implementation outcomes of acceptability, feasibility, and fidelity.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Treatment: Drugs
Anticipated trial start date 31/08/2021
Actual trial start date
Anticipated date of last follow up 31/03/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 700
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
R01AI155052 U.S. NIH Grant/Contract Award Number
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Outcome Assessors
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Treatment drug Drug: Cabotegravir/ Rilpivirine For initial injection participants will be given CABENUVA 600-mg/900-mg Kit: (single-dose vial of 600 mg/3 mL (200 mg/mL) cabotegravir , singledose vial of 900 mg/3 mL (300 mg/mL) rilpivirin). For subsequent injections participants will be given CABENUVA 400-mg/600-mg Kit: (single-dose vial of 400 mg/2 mL (200 mg/mL) cabotegravir, singledose vial of 600 mg/2 mL (300 mg/mL) rilpivirine) CABENUVA® is owned by or licensed to the ViiV Healthcare group of companies, GlaxoSmithKline Research Triangle Park, NC 27709 Drug: Intramuscular depo-medroxyprogesterone acetate (IM DMPA) DMPA (150 mg of depo-medroxyprogesterone acetate (MPA)/ml IMI) is the most commonly used injectable contraceptive worldwide) 24 Weeks Drug: Cabotegravir/ Rilpivirine For initial injection participants will be given CABENUVA 600-mg/900-mg Kit: (single-dose vial of 600 mg/3 mL (200 mg/mL) cabotegravir , singledose vial of 900 mg/3 mL (300 mg/mL) rilpivirin). For subsequent injections participants will be given CABENUVA 400-mg/600-mg Kit: (single-dose vial of 400 mg/2 mL (200 mg/mL) cabotegravir, singledose vial of 600 mg/2 mL (300 mg/mL) rilpivirine) CABENUVA® is owned by or licensed to the ViiV Healthcare group of companies, GlaxoSmithKline Research Triangle Park, NC 27709 Drug: Intramuscular depo-medroxyprogesterone acetate (IM DMPA) DMPA (150 mg of depo-medroxyprogesterone acetate (MPA)/ml IMI) is the most commonly used injectable contraceptive worldwide) 21
Experimental Group Treatment drug Drug: Cabotegravir/ Rilpivirine For initial injection participants will be given CABENUVA 600-mg/900-mg Kit: (single-dose vial of 600 mg/3 mL (200 mg/mL) cabotegravir , singledose vial of 900 mg/3 mL (300 mg/mL) rilpivirin). For subsequent injections participants will be given CABENUVA 400-mg/600-mg Kit: (single-dose vial of 400 mg/2 mL (200 mg/mL) cabotegravir, singledose vial of 600 mg/2 mL (300 mg/mL) rilpivirine) CABENUVA® is owned by or licensed to the ViiV Healthcare group of companies, GlaxoSmithKline Research Triangle Park, NC 27709 Drug: Etonogestrel (ETG) implant Contraceptive progestin implants are thin rods inserted under the skin of a woman's arm. 24 Weeks Drug: Cabotegravir/ Rilpivirine For initial injection participants will be given CABENUVA 600-mg/900-mg Kit: (single-dose vial of 600 mg/3 mL (200 mg/mL) cabotegravir , singledose vial of 900 mg/3 mL (300 mg/mL) rilpivirin). For subsequent injections participants will be given CABENUVA 400-mg/600-mg Kit: (single-dose vial of 400 mg/2 mL (200 mg/mL) cabotegravir, singledose vial of 600 mg/2 mL (300 mg/mL) rilpivirine) CABENUVA® is owned by or licensed to the ViiV Healthcare group of companies, GlaxoSmithKline Research Triangle Park, NC 27709 Drug: Etonogestrel (ETG) implant Contraceptive progestin implants are thin rods inserted under the skin of a woman's arm. 21
Experimental Group Treatment drug Drug: Cabotegravir/ Rilpivirine For initial injection participants will be given CABENUVA 600-mg/900-mg Kit: (single-dose vial of 600 mg/3 mL (200 mg/mL) cabotegravir , singledose vial of 900 mg/3 mL (300 mg/mL) rilpivirin). For subsequent injections participants will be given CABENUVA 400-mg/600-mg Kit: (single-dose vial of 400 mg/2 mL (200 mg/mL) cabotegravir, singledose vial of 600 mg/2 mL (300 mg/mL) rilpivirine) CABENUVA® is owned by or licensed to the ViiV Healthcare group of companies, GlaxoSmithKline Research Triangle Park, NC 27709 Drug: Levonorgestrel Contraceptive estrogen implants are thin rods inserted under the skin of a woman's arm. 24 Weeks Drug: Cabotegravir/ Rilpivirine For initial injection participants will be given CABENUVA 600-mg/900-mg Kit: (single-dose vial of 600 mg/3 mL (200 mg/mL) cabotegravir , singledose vial of 900 mg/3 mL (300 mg/mL) rilpivirin). For subsequent injections participants will be given CABENUVA 400-mg/600-mg Kit: (single-dose vial of 400 mg/2 mL (200 mg/mL) cabotegravir, singledose vial of 600 mg/2 mL (300 mg/mL) rilpivirine) CABENUVA® is owned by or licensed to the ViiV Healthcare group of companies, GlaxoSmithKline Research Triangle Park, NC 27709 Drug: Levonorgestrel Contraceptive estrogen implants are thin rods inserted under the skin of a woman's arm. 21
Experimental Group Treatment drug For initial injection participants will be given CABENUVA 600-mg/900-mg Kit: (single-dose vial of 600 mg/3 mL (200 mg/mL) cabotegravir , singledose vial of 900 mg/3 mL (300 mg/mL) rilpivirin). For subsequent injections participants will be given CABENUVA 400-mg/600-mg Kit: (single-dose vial of 400 mg/2 mL (200 mg/mL) cabotegravir, singledose vial of 600 mg/2 mL (300 mg/mL) rilpivirine) CABENUVA® is owned by or licensed to the ViiV Healthcare group of companies, GlaxoSmithKline Research Triangle Park, NC 27709 24 Weeks For initial injection participants will be given CABENUVA 600-mg/900-mg Kit: (single-dose vial of 600 mg/3 mL (200 mg/mL) cabotegravir , singledose vial of 900 mg/3 mL (300 mg/mL) rilpivirin). For subsequent injections participants will be given CABENUVA 400-mg/600-mg Kit: (single-dose vial of 400 mg/2 mL (200 mg/mL) cabotegravir, singledose vial of 600 mg/2 mL (300 mg/mL) rilpivirine) CABENUVA® is owned by or licensed to the ViiV Healthcare group of companies, GlaxoSmithKline Research Triangle Park, NC 27709 21
Control Group Treatment drug Drug: Intramuscular depo-medroxyprogesterone acetate (IM DMPA) DMPA (150 mg of depo-medroxyprogesterone acetate (MPA)/ml IMI) is the most commonly used injectable contraceptive worldwide) 24 Weeks Drug: Intramuscular depo-medroxyprogesterone acetate (IM DMPA) DMPA (150 mg of depo-medroxyprogesterone acetate (MPA)/ml IMI) is the most commonly used injectable contraceptive worldwide) 21 Uncontrolled
Experimental Group Treatment drug Drug: Cabotegravir/ Rilpivirine For initial injection participants will be given CABENUVA 600-mg/900-mg Kit: (single-dose vial of 600 mg/3 mL (200 mg/mL) cabotegravir , singledose vial of 900 mg/3 mL (300 mg/mL) rilpivirin). For subsequent injections participants will be given CABENUVA 400-mg/600-mg Kit: (single-dose vial of 400 mg/2 mL (200 mg/mL) cabotegravir, singledose vial of 600 mg/2 mL (300 mg/mL) rilpivirine) CABENUVA® is owned by or licensed to the ViiV Healthcare group of companies, GlaxoSmithKline Research Triangle Park, NC 27709 48 Weeks Drug: Cabotegravir/ Rilpivirine For initial injection participants will be given CABENUVA 600-mg/900-mg Kit: (single-dose vial of 600 mg/3 mL (200 mg/mL) cabotegravir , singledose vial of 900 mg/3 mL (300 mg/mL) rilpivirin). For subsequent injections participants will be given CABENUVA 400-mg/600-mg Kit: (single-dose vial of 400 mg/2 mL (200 mg/mL) cabotegravir, singledose vial of 600 mg/2 mL (300 mg/mL) rilpivirine) CABENUVA® is owned by or licensed to the ViiV Healthcare group of companies, GlaxoSmithKline Research Triangle Park, NC 27709 275
Control Group Treatment drug Drug: NNRTI, PI, or INSTI-containing 1st or 2nd line ART regimens ART that concurrently contains combinations of nonnucleoside reverse transcriptase inhibitors (NNRTIs), such as efavirenz, and protease-inhibitors (PIs), such as atazanavir/ritonavir or lopinavir/ritonavir, or integrase inhibitors (INSTIs), such as raltegravir or dolutegravir 48 Weeks Drug: NNRTI, PI, or INSTI-containing 1st or 2nd line ART regimens ART that concurrently contains combinations of nonnucleoside reverse transcriptase inhibitors (NNRTIs), such as efavirenz, and protease-inhibitors (PIs), such as atazanavir/ritonavir or lopinavir/ritonavir, or integrase inhibitors (INSTIs), such as raltegravir or dolutegravir 275 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Inclusion Criteria (PK study): • Female sex, • HIV-positive (for PK groups #1-4 and hybrid trial) or HIV-uninfected (for PK group #5 only), • Age 15-24 years at the time of enrollment, • Documented or confirmed viral suppression for HIV (defined as <40 copies/mL) within 6 months prior to study screening, • Have been on the study oral drug for at least 4 weeks for the PK groups #1-4, • Have initiated and intends to use DMPA or implant for at least another three or 6 months, respectively, • Willing to undergo phlebotomy every 4-12 weeks for the duration of the study period • Able to consent or assent (with parental consent) for study participation in English or Kiswahili Inclusion Criteria (Hybrid trial): • Female sex, • HIV-positive, • Age 15-24 years at the time of enrollment, • Documented or confirmed viral suppression for HIV (defined as <40 copies/mL) within 6 months prior to study screening, • Willing to undergo phlebotomy every 4-12 weeks for the duration of the study period, • Able to consent or assent (with parental consent) for study participation in English or Kiswahili Exclusion Criteria (PK study): • Already be on ART that concurrently contains combinations of nonnucleoside reverse transcriptase inhibitors (NNRTIs), such as efavirenz, and protease-inhibitors (PIs), such as atazanavir/ritonavir or lopinavir/ ritonavir, or integrase inhibitors (INSTIs), such as raltegravir or dolutegravir • Currently pregnant or intends to become pregnant or breastfeeding within the next 12 or 24 weeks for DMPA or implant groups, respectively, • Have had unprotected sex in the last two weeks or be currently pregnant via urine pregnancy testing, • Use or anticipated use of drugs for the duration of the study period known to interact with hormonal implants or the study ART regimen, • Current or planned concomitant use of other hormonal contraceptives, • Be obese (BMI≥30), • Evidence of Hepatitis B virus (HBV) infection based on the results of testing for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV Deoxyribonucleic acid (DNA) as follows: positive for HBsAg being excluded or negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded (of note, participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded). • Serum ALT>5x ULN at the time of screening, • Serum creatinine >2.5x ULN at the time of screening. Exclusion Criteria (Hybrid trial): • Already be on ART that concurrently contains combinations of nonnucleoside reverse transcriptase inhibitors (NNRTIs), such as efavirenz, and protease-inhibitors (PIs), such as atazanavir/ritonavir or lopinavir/ ritonavir, or integrase inhibitors (INSTIs), such as raltegravir or dolutegravir • Currently pregnant or intends to become pregnant or breastfeeding within the next one year, • Have had unprotected sex in the last two weeks or be currently pregnant via urine pregnancy testing, • Use or anticipated use of drugs for the duration of the study period known to interact with the study ART regimen, • Evidence of Hepatitis B virus (HBV) infection based on the results of testing for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV Deoxyribonucleic acid (DNA) as follows: positive for HBsAg being excluded or negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded (of note, participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded). • Serum ALT>5x ULN at the time of screening, • Serum creatinine >2.5x ULN at the time of screening. Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year 15 Year(s) 24 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 24/06/2021 Moi University Teaching and Referral Hospital IREC
Ethics Committee Address
Street address City Postal code Country
Nandi road. Eldoret 30100 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 02/04/2021 University of Washington IRB
Ethics Committee Address
Street address City Postal code Country
Brooklyn Ave. NE, Box 359470 Seattle, WA 98195-9470 Seattle, Washington 4333 United States of America
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome These geometric means will be compared to HIV-negative groups recruited in this study (for the DMPA comparator) or from the PARVI study (for the implants comparator), 12 or 24 weeks after DMPA or implant initiation
Primary Outcome The proportion of participants with viral suppression ( via HIV viral load <40 copies/ mL) in the intervention vs. control arms 48 weeks after study enrollment
Secondary Outcome Adherence and persistence to ART For secondary outcomes of adherence and persistence to ART over the preceding month prior to the VL evaluation and persistence/average MPR since study enrollment. 3, 6, and 12 months after method initiation
Secondary Outcome Time to LA contraceptive uptake, or incident use, among participants who are not already using a LA contraceptive method at enrollment and wish to delay pregnancy. 3, 6, and 12 months after method initiation
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Moi Teaching and Referral Hospital Nandi road Eldoret 30100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
NIH 5601 FISHERS LANE ROCKVILLE United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Univesity of Washington 4333 Brooklyn Ave NE Seattle 981959472 United States of America University
COLLABORATORS
Name Street address City Postal code Country
University of Washington 325 9th Ave Seattle 981050000 United States of America
Moi University Nandi Road Eldoret 30100 Kenya
Indiana University School of Medicine 340 W 10th St Indianopolis 462020000 United States of America
University of Nebraska Medical Center 985100 Nebraska Medical Center Omaha 681955100 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Rena Patel rcpatel@uw.edu +16503530718 325 9th Ave
City Postal code Country Position/Affiliation
Seattle 981050000 United States of America University of Washington
Role Name Email Phone Street address
Principal Investigator Edwin Were eowere@gmail.com +254705756103 Nandi road
City Postal code Country Position/Affiliation
Eldoret 30100 Kenya Moi University
Role Name Email Phone Street address
Public Enquiries Edwin Were eowere@gmail.com +254705756103 Nandi road
City Postal code Country Position/Affiliation
Eldoret 30100 Kenya Moi University
Role Name Email Phone Street address
Scientific Enquiries Rena Patel rcpatel@uw.edu +16503530718 325 9th Ave
City Postal code Country Position/Affiliation
Seattle 981050000 United States of America University of Washington
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes De-identified IPD that underlies the results reported in a publication will be provided. Data sharing will begin 9 months after article publication and will be available for up to 36 months. Data will be made available to qualified researchers whose proposed research has received IRB approval. The data will be provided through a data repository following the execution of a data-sharing agreement. Study Protocol Starting 9 months and ending 36 months after article publication Investigators whose proposed use of the data has been approved by the investigators
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information