Clinical trial NCT05580666: Reducing Mortality in Adults With Advanced HIV Disease (REVIVE)
Official title: Reducing Mortality in Adults With Advanced HIV Disease, a Double Blinded Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: HIV Disease Progression
Keywords: Human immunodeficiency virus
Antiretroviral therapy
Azithromycin
Mortality
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2022-10-14
Enrollment: 8000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blinded placebo-controlled randomized trial
Primary purpose: TREATMENT

Brief summary: A double blinded, placebo-controlled, multicenter trial to evaluate effectiveness of azithromycin prophylaxis on mortality in advanced HIV.

Detailed description: All participants in the REVIVE trial will be randomized (1:1) at the time of study entry to receive azithromycin prophylaxis or placebo for 28 days and will be followed for 24 weeks to determine the primary outcome measure. Total follow up duration will be 48 weeks.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years
2. Documented HIV infection
3. CD4 count criteria:

   i. CD4 count ≤ 100 cells/mm3 within past 4 weeks; or

   ii. Documented CD4 nadir ≤ 100 cells/mm3 and complete interruption of ART for ≥ 6 months; or

   iii. Documented CD4 count ≤ 100 cells/mm3 if ART-naive
4. Ability to initiate or re-initiate ART, or switch to an effective ART regimen if failing current therapy, within 4 weeks of enrolment

Exclusion Criteria:

1. Contraindications to azithromycin:

   i. Hypersensitivity to azithromycin, erythromycin, or any macrolide antibiotic; or

   ii. Personal or family history of QT-prolongation
2. Severe illness requiring immediate or continued hospitalization (this will be in the judgment of site investigators)
3. Off-label azithromycin prophylaxis or requirement for prolonged (\> 7 days) azithromycin (or macrolide) therapy

Primary outcomes:
measure: All-cause mortality
timeFrame: 24 weeks after randomization
Secondary outcomes:
measure: All-cause mortality
timeFrame: 12 weeks after randomization
measure: Hospitalization
timeFrame: 24 weeks after randomization
measure: Composite of hospitalization or all-cause mortality
timeFrame: 24 weeks after randomization
Other outcomes:
Locations:
city: Gaborone
country: Botswana
facility: University of Botswana
city: Brazzaville
country: Congo
facility: Fondation Congolaise pour la Recherche Médicale
city: Abidjan
country: Côte D'Ivoire
facility: Centre de Prise en Charge et de Formation
city: Abidjan
country: Côte D'Ivoire
facility: Centre Intégré de Recherches Biocliniques d'Abidjan (CIRBA)
city: Abidjan
country: Côte D'Ivoire
facility: Centre médical de suivi des donneurs de sang (CMSDS)
city: Abidjan
country: Côte D'Ivoire
facility: Unité de Soins Ambulatoires et de conseils (USAC)
city: Ādama
country: Ethiopia
facility: Adama Hospital Medical College
city: Kumasi
country: Ghana
facility: Komfo Anokye Teaching Hospital
city: Lilongwe
country: Malawi
facility: Lilongwe Medical Relief Fund/UNC Project
city: Maputo
country: Mozambique
facility: Faculty of Medicine, Eduardo Mondlane University
city: Abuja
country: Nigeria
facility: University of Abuja Teaching Hospital
city: Calabar
country: Nigeria
facility: University of Calabar Teaching Hospital
city: Enugu
country: Nigeria
facility: University of Nigeria Teaching Hospital
city: Ibadan
country: Nigeria
facility: University College Hospital
city: Jos
country: Nigeria
facility: Jos University Teaching Hospital
city: Kano
country: Nigeria
facility: Aminu Kano Teaching Hospital
city: Lago
country: Nigeria
facility: Lagos University Teaching Hospital
city: Sokoto
country: Nigeria
facility: Usmanu Danfodiyo University Teaching Hos
city: Umuahia
country: Nigeria
facility: Federal Medical Center
city: Uyo
country: Nigeria
facility: University of Uyo Teaching Hospital
city: Yenagoa
country: Nigeria
facility: Niger Delta University Teaching Hospital
city: Kigali
country: Rwanda
facility: Centre Hospitalier Universitaire de Kigali (CHUK)
city: Freetown
country: Sierra Leone
facility: College of Medicine and Allied Health Sciences, University of Sierra Leone
city: Cape Town
country: South Africa
facility: Desmond Tutu Health Foundation
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital -New main building, Infectious Disease Clinic G26
city: Cape Town
country: South Africa
facility: New Somerset Hospital
city: Cape Town
country: South Africa
facility: Ubuntu Clinic, Site B, Khayelitsha, Wellcome Centre
city: Hlabisa
country: South Africa
facility: Africa Health Research Institute (AHRI)- Nkundusi Clinic
city: Hluhluwe
country: South Africa
facility: Africa Health Research Institute (AHRI)- Hluhluwe Clinic
city: Johannesburg
country: South Africa
facility: Wits Health Consortium (Pty) Ltd
city: Klerksdorp
country: South Africa
facility: The Aurum Institute
city: Mtubatuba
country: South Africa
facility: Africa Health Research Institute (AHRI)- KwaMsane Clinic
city: Mtubatuba
country: South Africa
facility: Africa Health Research Institute (AHRI)- Mpukunyoni Clinic
city: Mtubatuba
country: South Africa
facility: Africa Health Research Institute (AHRI)- Mtubatuba Clinic
city: Mtubatuba
country: South Africa
facility: Africa Health Research Institute (AHRI)- Somkhele Clinic
city: Pretoria
country: South Africa
facility: Steve Biko Academic Hospital, University of Pretoria
city: Randburg
country: South Africa
facility: Right to Care NPC, Esizayo Division
city: Rustenburg
country: South Africa
facility: The Aurum Institute
city: Mbeya
country: Tanzania
facility: National Institute for Medical Research (NIMR)
city: Moshi
country: Tanzania
facility: Kibong'oto Infectious Diseases Hospital
city: Moshi
country: Tanzania
facility: Kilimanjaro Clinical Research Institute
city: Mbarara
country: Uganda
facility: Mbarara Regional Referral hospital
city: Lusaka
country: Zambia
facility: The Center for Infectious Disease Research in Zambia (CIDRZ)- George Clinical Research Site
city: Lusaka
country: Zambia
facility: The Center for Infectious Disease Research in Zambia (CIDRZ)- Matero Clinical Research Site
city: Lusaka
country: Zambia
facility: The Center for Infectious Disease Research in Zambia (CIDRZ)-Chawama Clinical Research Site (CRS)
Study officials:
affiliation: Population Health Research Institute
name: John Eikelboom, MBBS, MSc, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cape Town
name: Sean Wasserman, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
References: