Ignite Creation Date:
2025-12-24 @ 9:16 PM
Ignite Modification Date:
2025-12-30 @ 7:26 PM
Study NCT ID:
NCT06250504
Status:
RECRUITING
Last Update Posted:
2024-04-17
First Post:
2023-12-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Long-Acting HIV Pre-Exposure Prophylaxis Integrated With Sexual and Reproductive Health - cRCT
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015658', 'term': 'HIV Infections'}], 'ancestors': [{'id': 'D000086982', 'term': 'Blood-Borne Infections'}, {'id': 'D003141', 'term': 'Communicable Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D015229', 'term': 'Sexually Transmitted Diseases, Viral'}, {'id': 'D012749', 'term': 'Sexually Transmitted Diseases'}, {'id': 'D016180', 'term': 'Lentivirus Infections'}, {'id': 'D012192', 'term': 'Retroviridae Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007153', 'term': 'Immunologic Deficiency Syndromes'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C584914', 'term': 'cabotegravir'}, {'id': 'C481671', 'term': 'Dapivirine'}, {'id': 'D003274', 'term': 'Contraceptive Devices, Female'}, {'id': 'D000069480', 'term': 'Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination'}, {'id': 'D000068698', 'term': 'Tenofovir'}, {'id': 'C562325', 'term': 'dolutegravir'}], 'ancestors': [{'id': 'D003273', 'term': 'Contraceptive Devices'}, {'id': 'D004864', 'term': 'Equipment and Supplies'}, {'id': 'D063065', 'term': 'Organophosphonates'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000068679', 'term': 'Emtricitabine'}, {'id': 'D003841', 'term': 'Deoxycytidine'}, {'id': 'D003562', 'term': 'Cytidine'}, {'id': 'D011741', 'term': 'Pyrimidine Nucleosides'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D000225', 'term': 'Adenine'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D003853', 'term': 'Deoxyribonucleosides'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}, {'id': 'D004338', 'term': 'Drug Combinations'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'The statistician and clinical team will not participate in the public randomisation. The statistician will remain blinded until the analysis plan has been finalised and the database is locked. Investigators remain blinded to allocation throughout. The participants and intervention delivery teams are not blinded'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'A hybrid phase 3B effectiveness implementation type 1a cluster randomised control trial (cRCT)'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 2000}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2024-02-27', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-04', 'completionDateStruct': {'date': '2026-03', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-04-16', 'studyFirstSubmitDate': '2023-12-15', 'studyFirstSubmitQcDate': '2024-02-01', 'lastUpdatePostDateStruct': {'date': '2024-04-17', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-02-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-07', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Sexual and reproductive health', 'timeFrame': '14 months', 'description': 'uptake of family planning, teenage pregnancies and sexually transmitted infection prevalence in each arm'}, {'measure': 'Improved socioeconomic outcomes', 'timeFrame': '14 months', 'description': 'Defined as proportion in school (aged \\<= 18) or unemployed (aged \\>18) and/or food secure (no recent experience of hunger) in each arm.'}, {'measure': 'improved mental health', 'timeFrame': '14 months', 'description': 'Proportion with PHQ9 score consistent with common mental disorder in each arm'}], 'primaryOutcomes': [{'measure': 'Uptake PrEP', 'timeFrame': 'This will be evaluated among participants aged 16-30 years in the cross-sectional surveys at 14 months', 'description': 'Defined as the proportion of young people who have taken up any PrEP (oral, injectable, ring, or PEP).'}, {'measure': 'Retention on PrEP', 'timeFrame': 'This will be measured in the clinical cohort of consenting clinic attendeeswho start or are on PrEP/PEP during the first 10 months of the trial.', 'description': 'Defined as attending at least one follow-up appointment after PrEP/PEP initiation, including for HIV testing.'}], 'secondaryOutcomes': [{'measure': 'The prevalence of transmissible HIV.', 'timeFrame': '14 months', 'description': 'We will measure this outcome as the proportion of those living with HIV and have a detectable HIV viral load, defined as having an HIV viral load of \\>= 400 copies per ml, during our final survey round.'}, {'measure': 'Uptake of risk informed HIV prevention', 'timeFrame': '14 months', 'description': 'Defined as the proportion of 16-30 year olds who are aware of their HIV status and have undergone a HIV risk assessment to inform HIV prevention and/or are on/start HIV treatment if living with HIV.'}, {'measure': 'PrEP Reach (Adoption)', 'timeFrame': '14 months', 'description': 'Proportion of those at greatest risk adopting (taking up) PrEP or PEP in each arm. Greatest risk is defined as an aggregate exposure disaggregated by gender that includes any of the following factors: out of school (aged \\<= 18) or unemployed (aged \\>18) and/or engaged in transactional sex or sex work and/or harmful alcohol use (AUDIT scale) and/or experience physical, sexual or emotional violence (validated tool) and/or food poverty (recent experience of hunger)'}, {'measure': 'PrEP delivery cost and cost-effectiveness', 'timeFrame': '14 months', 'description': 'cost per effective PrEP uptake in each arm'}, {'measure': 'Adverse events', 'timeFrame': '14 months', 'description': 'Proportion discontinue or switch due to adverse events in each arm'}, {'measure': 'Proportion of men and women aged 16-30 at risk of acquiring HIV or transmitting HIV', 'timeFrame': '14 months', 'description': 'If living with HIV (a detectable viral load + condomless sex + not on ART), or, if not living with HIV (condomless sex + not on PrEP)'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['HIV Infections']}, 'descriptionModule': {'briefSummary': 'The goal of this hybrid (1a) Cluster Randomised Controlled Trial phase 3B trial is to evaluate the effectiveness and implementation of offering a choice of HIV Pre-Exposure Products (PrEP) through community-based sexual and reproductive health services, on PrEP uptake and retention, and population prevalence of sexually transmissible HIV amongst adolescents and young adults living in rural South Africa.\n\nResearchers will compare adding the choice of long-acting PrEP, i.e. two monthly injectable cabotegravir (CAB LA) or dapiravine vaginal ring and HIV post exposure prophylaxis packs to daily oral PrEP integrated with community-based SRH in the 20 intervention clusters with standard of care (SoC), daily oral PrEP integrated with community-based SRH in the 20 control clusters, on uptake and retention on PrEP. We hypothesise that offering a choice of long-acting or oral PrEP and PEP within the community-based delivery of SRH services will overcome the challenges and barriers to effective use of oral daily PrEP and lead to a population-level effect on uptake and retention on PrEP and thus the prevalence of sexually transmissible HIV amongst 15-30 year olds living in rural KwaZulu-Natal, South Africa.', 'detailedDescription': 'This is a pragmatic trial of adding in a choice of South African Health Products Registration Authority (SAHPRA) approved newer PrEP products - APRETUDE (cabotegravir) 600 mg\\\\3 mL: DAPIRING (Dapivirine) 25mg Vaginal Ring:56/20.2.8/0979 (22/11/2022) - to the current national department of health approved oral daily PrEP with TVF/FTC (Tenofovir disoproxil/emtricitabine), Objective 1. To measure the effectiveness of the choice of oral and long-acting PrEP, including injectable (CAB LA) and vaginal ring (DapiRing), and post exposure prophylaxis (PEP) on increasing effective uptake (adoption), retention, and adherence of PrEP compared to oral PrEP in young people aged 15-30 in rural South Africa and to estimate the preliminary effect on transmissible HIV and HIV incidence.\n\nObjective 2. To understand real-world implementation:\n\n2.1 To explore the acceptability, appropriateness, preference, and reach of CABLA from the perspective of young people aged 15-30 and their communities in rural South Africa 2.2 To understand the feasibility, affordability, and scalability of delivering CABLA through community-based PrEP with SRH.\n\n2.3 To identify implementation challenges and practical solutions for CABLA initiation, laboratory monitoring (e.g. RNA testing), and safe stopping within nurse-led and rural community-based clinical settings 2.4 To evaluate the safety and tolerability of CABLA compared to oral PrEP'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '30 Years', 'minimumAge': '15 Years', 'genderBased': True, 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\nAll young men and women aged 15-30 who are residing in the 40 administrative clusters in the study district and attend any integrated SRH/HIV service\n\nDocumented HIV negative test\n\nSuitable for PrEP and/or already on PrEP\n\nWeight \\> 35 kg\n\nUnderstand the required dosing schedule and HIV testing.\n\nAware that details can be shared with a peer navigator to support their follow-up\n\nIf pregnant or breast feeding and/or planning to become pregnant participant can be offered CAB LA, if risk of acquiring HIV out weighs unknown risk of CAB LA, but must understand that safety in pregnancy or breast feeding for CAB LA has not been established and oral daily PrEP is a safe alternative.\n\nExclusion Criteria:\n\nHistory or presence of allergy to the study drugs or their components\n\nInvestigator assessment find them not suitable\n\nAdditional exclusion criteria for specific products:\n\nCAB LA: Taking medication that is contraindicated (Carbamazepine, oxcarbazepine, phenobarbital, phenytoin, Rifampin, rifapentine) and Severe mental health disorder, Hep B surface antigen positive, living with hepatitis C and not yet treated, or abnormal liver function tests (ALT more than two times the upper limit of normal)\n\nDapiRing: Pregnancy.'}, 'identificationModule': {'nctId': 'NCT06250504', 'acronym': 'LAPIS', 'briefTitle': 'Long-Acting HIV Pre-Exposure Prophylaxis Integrated With Sexual and Reproductive Health - cRCT', 'organization': {'class': 'OTHER', 'fullName': 'Africa Health Research Institute'}, 'officialTitle': 'Long-acting HIV Pre-Exposure Prophylaxis Integrated With Community-based Sexual and Reproductive Health in South Africa (LAPIS): A Hybrid (1a) Cluster Randomised Controlled Phase 3B Trial of Effectiveness and Implementation', 'orgStudyIdInfo': {'id': 'cRCT-PrEP-AC-001'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe', 'description': 'Tailored peer-led psychosocial support and social mobilisation into community based SRH and differentiated HIV care and prevention, including a choice of effective PrEP or PEP.\n\nAt the mobile AYFS in the intervention clusters nurses will offer the choice of either daily oral tenofovir/emtricitabine or injectable long acting cabotegravir (CAB LA) to be delivered to adolescents and young adults at risk of HIV acquisition. Those who decline will have the option of three monthly dapivarine vaginal rings or Post Exposure Prophylaxis (PEP) packs (tenofovir/lamuvidine/dolutegravir) to take home.\n\nPeer navigators will promote long-acting PrEP in addition to oral PrEP. As part of the peer mentorship package, the peer naviators will remind young people of their follow-up visits.', 'interventionNames': ['Drug: APRETUDE (cabotegravir) 600 mg\\3 mL', 'Drug: DAPIRING (Dapivirine) 25mg Vaginal Ring', 'Drug: tenofovir disoproxil and emtricitabine', 'Drug: Tenofovir Disoproxil, Lamuvidine and Dolutegravir']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Control (Enhanced SoC): Thetha Nami ngithethe nawe', 'description': 'Tailored peer-led psychosocial support and social mobilisation into community based SRH and differentiated HIV care and prevention, including oral tenofovir/emtricitabine PrEP.\n\nIn the mobile AYFS, young people are offered self-taken vaginal swabs or urine testing for sexually transmitted infections (STIs), family planning support and syndromic and aetiological management for STIs; HIV counselling and two POCT; immediate initiation of ART if living with HIV and oral tenofovir/emtricitabine PrEP if HIV test is negative and they are suitable.\n\nPeer navigators in control clusters will promote oral PrEP during their community based health promotion activities. As part of the peer mentorship package, the peer naviators will remind young people of their follow-up visits and if required accompany young people to the mobile clinics.', 'interventionNames': ['Drug: tenofovir disoproxil and emtricitabine']}], 'interventions': [{'name': 'APRETUDE (cabotegravir) 600 mg\\3 mL', 'type': 'DRUG', 'description': 'choice of 2-monthly injectable long acting cabotegravir. The initial visit will be followed by planned visit for the first injection, one month visit for second injection, and then 2-monthly CAB LA injections with repeat HIV testing and pregnancy testing, and referral to peer navigators for adherence and retention support. We will conduct HIV testing, STI testing, Hep B, Hep C, and safety bloods (Full Blood Count, Creatinine, Liver Function Tests) at baseline, HIV testing two monthly, and annual safety bloods, alongside annual STI testing.', 'armGroupLabels': ['Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe']}, {'name': 'DAPIRING (Dapivirine) 25mg Vaginal Ring', 'type': 'DRUG', 'description': 'The initial visit is followed by a 7-day phone call, 3-monthly follow-up. Each follow-up will include repeat HIV testing (POCT x2 and dry blood spots for HIV ELISA) and pregnancy testing, syndromic management of STIs, and referral to peer navigators for adherence support and PrEP/ART and if applicable contraception refills. Safely bloods (full blood count, creatinine, liver function tests) will follow national guidelines. Currently we aim to do baseline and annual safety bloods, alongside annual STI testing', 'armGroupLabels': ['Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe']}, {'name': 'tenofovir disoproxil and emtricitabine', 'type': 'DRUG', 'description': 'The initial visit is followed by a 7-day phone call, 3-monthly follow-up. Each follow-up will include repeat HIV testing (POCT x2 and dry blood spots for HIV ELISA) and pregnancy testing, syndromic management of STIs, and referral to peer navigators for adherence support and PrEP/ART and if applicable contraception refills. Safely bloods (full blood count, creatinine, liver function tests) will follow national guidelines. Currently we aim to do baseline and annual safety bloods, alongside annual STI testing', 'armGroupLabels': ['Control (Enhanced SoC): Thetha Nami ngithethe nawe', 'Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe']}, {'name': 'Tenofovir Disoproxil, Lamuvidine and Dolutegravir', 'type': 'DRUG', 'description': 'The initial visit is followed by a 7-day phone call, 3-monthly follow-up. Each follow-up will include repeat HIV testing (POCT x2 and dry blood spots for HIV ELISA) and pregnancy testing, syndromic management of STIs, and referral to peer navigators for adherence support and PrEP/ART and if applicable contraception refills. Safely bloods (full blood count, creatinine, liver function tests) will follow national guidelines. Currently we aim to do baseline and annual safety bloods, alongside annual STI testing', 'armGroupLabels': ['Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Somkele', 'state': 'KwaZulu-Natal', 'status': 'RECRUITING', 'country': 'South Africa', 'contacts': [{'name': 'Maryam Shahmanesh, PhD', 'role': 'CONTACT', 'email': 'm.shahmanesh@ucl.ac.uk'}], 'facility': 'Africa Health Research Institute', 'geoPoint': {'lat': -28.31667, 'lon': 32.1}}], 'centralContacts': [{'name': 'Maryam G Shahmanesh, MBBChir PhD', 'role': 'CONTACT', 'email': 'm.shahmanesh@ucl.ac.uk', 'phone': '+447776185572'}, {'name': 'Limakatso Lebina, MBBS PhD', 'role': 'CONTACT', 'email': 'l.lebina@ucl.ac.uk'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP', 'ICF', 'CSR', 'ANALYTIC_CODE'], 'timeFrame': 'After the primary analysis has been completed and publicaly shared', 'ipdSharing': 'YES'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Africa Health Research Institute', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}