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

NCT ID: NCT05118490

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 1000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-19
• Study Completion Date: 2025-12-31

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.

Conditions

HIV Seropositivity; Tuberculosis; Household Contact

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Group 1: People living with HIV infection without active TB

Group Type: EXPERIMENTAL

Daily rifapentine and isoniazid for 4 weeks

Intervention Type: DRUG

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

Weekly rifapentine and isoniazid for 12 weeks

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Daily rifapentine and isoniazid for 4 weeks

Intervention Type: DRUG

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

Weekly rifapentine and isoniazid for 12 weeks

Intervention Type: DRUG

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

Interventions

Daily rifapentine and isoniazid for 4 weeks

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

Intervention Type: DRUG

Weekly rifapentine and isoniazid for 12 weeks

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 13 years

2. Weight > 30 kg

3. HIV-seropositive

4. HIV viral load <400 copies/mL, defined as "virally suppressed," on an EFV or DTG-based ART regimen (see Section 3.6.2)

5. Candidates must meet WHO criteria for receiving TPT

1. Age ≥ 13 years

2. Weight > 30 kg

3. HIV-negative

4. Household contact of an adult with confirmed rifampicin-sensitive pulmonary TB

5. Candidates must meet WHO criteria for receiving TPT

Exclusion Criteria

1. Confirmed or suspected TB disease (evidenced by symptoms and/or clinical exam findings and/or chest radiographic findings suggestive of TB, positive mycobacterial culture or molecular TB testing or currently on TB treatment for active TB disease)

2. Likely to move from the study area during the study period

3. Known recent exposure to a TB case with resistance to isoniazid or rifampicin.

4. Previous treatment for active or latent TB for more than 30 days within the past 2 years

5. On nevirapine, etravirine, rilpivirine, PI-based, or raltegravir-containing ART regimens

6. Known sensitivity or intolerance to isoniazid or rifamycins

7. Suspected acute hepatitis or known chronic or unstable liver disease^

8. ALT > 3 times the upper limit of normal (ULN)

9. Total bilirubin > 2.5 times the ULN

10. Pregnancy or breastfeeding Females of childbearing potential who are unable or unwilling to use two forms of contraception**

11. On prohibited medications (see Appendix I)

Group 2: HIV-negative household contacts of an adult with confirmed pulmonary TB in Mozambique and Indonesia

1. Confirmed or suspected TB disease (evidenced by symptoms and/or clinical exam findings and/or chest radiographic findings suggestive of TB, positive mycobacterial culture or molecular TB testing or currently on TB treatment for active TB disease)

2. Likely to move from the study area during the study period

3. Known exposure to TB cases with resistance to isoniazid or rifampicin in the source case

4. Previous treatment for active or latent TB for >30 days within the past 2 years

5. Known sensitivity or intolerance to isoniazid or rifamycins

6. Suspected acute hepatitis or known chronic or unstable liver disease^

7. ALT > 3 times the upper limit of normal (ULN)

8. Total bilirubin > 2.5 times the ULN

9. Pregnancy or breastfeeding Females of childbearing potential who are unable or unwilling to use two forms of contraception**

10. On prohibited medications

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: collaborator

The Aurum Institute NPC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gavin Churchyard

Role: STUDY_CHAIR

Aurum Institute

Locations

The Byramjee Jeejeebhoy Medical Centre (BJGMC-JHU) CRS

Pune, Maharashtra, India

Yayasan KNCV - The Persahabatan Hospital, Jakarta

Jakarta, Jaya, Indonesia

Fundação Aurum (The Aurum Institute Mozambique)

Chokwé, Gaza Province, Mozambique

The Aurum Institute: Gavin J Churchyard Legacy Centre

Klerksdorp, North West, South Africa

Countries

India; Indonesia; Mozambique; South Africa

Other Identifiers

IRB00298999

Identifier Type: -

Identifier Source: org_study_id