Bedaquiline Roll-out Evidence in Contacts and People Living With HIV to Prevent TB
NCT Number: NCT06568484
Acronym: BREACH-TB
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Tuberculosis, Latent
Interventions: DRUG: Bedaquiline|COMBINATION_PRODUCT: Isoniazid, rifapentine|DRUG: Levofloxacin
Sponsor: Johns Hopkins University
Collaborators: Elizabeth Glaser Pediatric AIDS Foundation|United States Agency for International Development (USAID)|Johnson & Johnson
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 2530
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2024-11
Completion Date: 2027-11
Locations: Aurum Tembisa CRS, Tembisa, Gauteng, 1632, South Africa|Perinatal HIV Research Unit (PHRU) - Matlosana, Klerksdorp, North West Province, 2574, South Africa|Aurum Institute Klerksdorp CRS, Klerksdorp, North West, 2571, South Africa

Summary:
A Phase III, open-label, multicenter, non-inferiority trial, to compare the efficacy and safety of 4 weeks of bedaquiline (BDQ) versus a World Health Organization (WHO) -recommended regimen for preventing confirmed or probable tuberculosis disease (TBD) during 96 weeks of follow-up among people living with HIV (PLHIV) and high-risk Close Contacts (CC) of adults with Drug Susceptible (DS) or Rifampin Resistant (RR) TB.

Primary Outcome Measures: Efficacy: Number of enrolled participants (PLHIV, contacts of DS-TB or RR-TB) who are diagnosed with bacteriologically confirmed or probable / (if adult), and confirmed or unconfirmed (if child) TB disease at the end of the follow-up period, Number (per person-years) of participants diagnosed with confirmed or probable (if adult) and unconfirmed or confirmed (if child) TB disease, compared between the comparator arm and investigational (BDQ) arm and expressed as the averted events ratio (AER), Up to 96 weeks post-treatment initiation|Safety: Cumulative number of enrolled participants (PLHIV, contacts of DS-TB or RR-TB) who permanently discontinue the assigned study regimen due to an adverse drug reaction, Proportion of individuals who permanently discontinue assigned study regimen due to an adverse drug reaction, compared between the comparator arm and investigational (BDQ) arm., Varies by treatment regimen (1 month, 3 months, or 6 months)
Secondary Outcome Measures: Efficacy Composite Outcome: # of enrolled participants (PLHIV, contacts of DS-TB, RR-TB) who reach a composite outcome of bacteriologically confirmed, probable, or possible (if adult) and confirmed or unconfirmed (if child) TBD or death from any cause, Number, per person-years, of participants diagnosed with bacteriologically confirmed, probable, or possible (if adult) and confirmed or unconfirmed (if child) TB disease or death from any cause, compared between the comparator arm and investigational (BDQ) arm and expressed as the AER, Up to weeks 96 post-treatment initiation|Secondary Endpoints of Adherence: Proportion of participants who have taken at least 90% of the doses within the specified timeframe of the assigned regimen, The absolute difference in proportions of the number of participants who have taken at least 90% of the doses within the specified timeframe of the participants assigned regimen, and the corresponding 95% confidence interval, Varies by treatment regimen duration (1 month, 3 months, or 6 months)|Secondary Safety Endpoint: Cumulative number of enrolled participants (PLHIV, contacts of DS-TB or RR-TB) who experience a grade 3 or higher AE, Proportion of individuals who experience a grade 3 or higher AE, compared between the comparator arm and investigational (BDQ) arm, Varies by treatment regimen duration (1 month, 3 months, or 6 months)