Reducing Mortality in Adults With Advanced HIV Disease (REVIVE) (REVIVE)

• ClinicalTrials.gov Identifier: NCT05580666
• Recruitment Status: Recruiting
• First Posted: October 14, 2022
• Last Update Posted: March 26, 2024
• Sponsor: Population Health Research Institute
• Information provided by (Responsible Party): Population Health Research Institute

Tracking Information

• First Submitted Date: October 11, 2022
• First Posted Date: October 14, 2022
• Last Update Posted Date: March 26, 2024
• Actual Study Start Date: May 8, 2023
• Estimated Primary Completion Date: May 31, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 13, 2022)

All-cause mortality [ Time Frame: 24 weeks after randomization ]

All-cause mortality over the first 24 weeks after randomization

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 13, 2022)

• All-cause mortality [ Time Frame: 12 weeks after randomization ]
  All-cause mortality over the first 12 weeks after randomization
• Hospitalization [ Time Frame: 24 weeks after randomization ]
  Hospitalization over the first 24 weeks after randomization
• Composite of hospitalization or all-cause mortality [ Time Frame: 24 weeks after randomization ]
  Composite of hospitalization or all-cause mortality over the first 24 weeks after randomization

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Reducing Mortality in Adults With Advanced HIV Disease (REVIVE)
• Official Title: Reducing Mortality in Adults With Advanced HIV Disease, a Double Blinded Randomized Trial
• 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.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Double blinded placebo-controlled randomized trial

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double blinded placebo-controlled

Primary Purpose: Treatment

• Condition: HIV Disease Progression

Intervention

• Drug: Azithromycin Oral Tablet
  Antimicrobial therapy
• Drug: Placebo oral tablet
  Inert ingredients

Study Arms

• Experimental: Oral Azithromycin 250 mg once daily
  Active Azithromycin tablet
  Intervention: Drug: Azithromycin Oral Tablet
• Placebo Comparator: Oral matching placebo, once daily
  Matching placebo tablet
  Intervention: Drug: Placebo oral tablet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 13, 2022): 8000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 1, 2028
• Estimated Primary Completion Date: May 31, 2028 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: REVIVE Study Coordinator; 905-297-3479; revive@phri.ca

• Listed Location Countries: Botswana, Côte D'Ivoire, Congo, Ethiopia, Ghana, Malawi, Mozambique, Nigeria, Rwanda, Sierra Leone, South Africa, Tanzania, Uganda, Zambia

Administrative Information

• NCT Number: NCT05580666
• Other Study ID Numbers: PHRI.REVIVE
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Population Health Research Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Population Health Research Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: John Eikelboom, MBBS, MSc, FRCPC; Population Health Research Institute
• Principal Investigator: Sean Wasserman, MBChB, PhD; University of Cape Town

• PRS Account: Population Health Research Institute
• Verification Date: March 2024