Comparing Treatment Completion Of Daily Rifapentine & Isoniazid For One Month (1HP) To Weekly High Dose Rifapentine & Isoniazid For 3 Months (3HP) In Persons Living With HIV and in Household Contacts of Recently Diagnosed Tuberculosis Patients

Phase 4

Recruiting

• Conditions: Tuberculosis; Household Contact; HIV Seropositivity
• Interventions: Drug: Daily rifapentine and isoniazid for 4 weeks; Drug: Weekly rifapentine and isoniazid for 12 weeks

• Registration Number: NCT05118490
• Lead Sponsor: The Aurum Institute NPC

Brief Summary

A multicenter, randomized, stratified, open-label, phase IV trial among HIV-positive persons (PLHIV) on antiretroviral therapy (ART), or HIV-negative household contacts of patients with rifampicin-sensitive pulmonary tuberculosis (TB), who do not have evidence of active TB.

Detailed Description

Participants will be stratified by indication for tuberculosis (TB) preventive treatment (TPT) - HIV seropositive persons or HIV-negative household contact of person with infectious TB - and will receive either one of two TB preventive therapy regimens:

Group 1: People living with HIV infection without active TB

Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP)

Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP)

Arm A (n=250): 250 participants age ≥13 years of age who are HIV seropositive and taking ART who do not have evidence of active TB will be recruited from local clinics. After being consented, screened, and randomized, participants in Arm A will receive the 1HP regimen once daily for 4 weeks (28 doses).

Study events include a health history, physical exam, TB symptom screen, symptom screen for adverse events (AEs), adherence checks during 1HP, and clinic visits at months 1, 2, and 6, at the least. Safety labs for liver function will be checked as clinically indicated.

Arm B (n=250): 250 participants age ≥13 years of age who are HIV seropositive and taking ART who do not have evidence of active TB will be recruited from local clinics. After being consented, screened, and randomized, participants in Arm B will receive the 3HP regimen once weekly for 12 weeks (12 doses).

Study events include a health history, physical exam, TB symptom screen, symptom screen for adverse events (AEs), adherence checks during 3HP, and clinic visits at months 1, 2, 3, and 6, at the least. Safety labs for liver function will be checked as clinically indicated.

Group 2: HIV-negative household contacts of newly diagnosed adults with rifampicin-sensitive pulmonary TB.

Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP)

Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP)

Arm A (n=250): 250 participants age ≥13 years of age who are HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB who do not have evidence of active TB will be recruited from local clinics and households of active cases. After being consented, screened, and randomized, participants in Arm A will receive the 1HP regimen once daily for 4 weeks (28 doses).

Study events include a health history, physical exam, TB symptom screen, symptom screen for adverse events (AEs), adherence checks during 1HP, and clinic visits at months 1, 2, and 6, at the least. Safety labs for liver function will be checked as clinically indicated.

Arm B (n=250): 250 participants age ≥13 years of age who are HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB who do not have evidence of active TB will be recruited from local clinics and households of active cases. After being consented, screened, and randomized, participants in Arm B will receive the 3HP regimen once weekly for 12 weeks (12 doses).

Study events include a health history, physical exam, TB symptom screen, symptom screen for adverse events (AEs), adherence checks during 3HP, and clinic visits at months 1, 2, 3, and 6, at the least. Safety labs for liver function will be checked as clinically indicated.

Study Timeline

• Study First Submitted: 2021-10-26
• Study First Submitted QC: 2021-11-11
• Study First Posted: 2021-11-12
• Study Start: 2023-07-19
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-15
• Last Update Posted: 2024-03-18
• Primary Completion: 2024-10-28
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: People living with HIV infection without active TB	Daily rifapentine and isoniazid for 4 weeks	-
Group 1: People living with HIV infection without active TB	Weekly rifapentine and isoniazid for 12 weeks	-
Group 2: HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB	Daily rifapentine and isoniazid for 4 weeks	-
Group 2: HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB	Weekly rifapentine and isoniazid for 12 weeks	-

Primary Outcome Measures

Name	Time	Method
Treatment adherence- pill count	from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2) , to be reported at end of trial	Completion of TPT with \>90% adherence documented by pill count (both groups, Arms A and B)
Treatment adherence- electronic monitoring device (EMD)	from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2) , to be reported at end of trial	Completion of TPT with \>90% adherence documented by pill count (both groups, Arms A and B)
Early treatment discontinuation	from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2), to be reported at end of trial	discontinuation of study medications because of side effects (both groups, Arms A and B)
Treatment adherence- self-report	from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2) , to be reported at end of trial	Completion of TPT with \>90% adherence documented by self-report (both groups, Arms A and B)
Adverse Events	from study entry at Day 0 through Month 6 (Week 24), to be reported at end of trial	Occurrence of Grade 2 or higher targeted safety events (both groups, Arms A and B). Targeted safety events are hypersensitivity syndrome, rash, seizure, peripheral neuropathy, hepatotoxicity, nausea and vomiting, and drug-related fever.

Secondary Outcome Measures

Name	Time	Method
Cost-effectiveness	from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2) , to be reported at end of trial	Incremental cost-effectiveness of 1HP and 3HP (compared to each other, \^ months of isoniazid (6H), and no treatment) using a societal perspective.

Trial Locations

Locations (4)

Yayasan KNCV - The Persahabatan Hospital, Jakarta; 🇮🇩 Jakarta, Jaya, Indonesia

The Aurum Institute: Gavin J Churchyard Legacy Centre; 🇿🇦 Klerksdorp, North West Province, South Africa

Fundação Aurum (The Aurum Institute Mozambique); 🇲🇿 Chokwé, Gaza, Mozambique

The Byramjee Jeejeebhoy Medical Centre (BJGMC-JHU) CRS; 🇮🇳 Pune, Maharashtra, India