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

NCT05118490 | Active Not Recruiting Phase 4

• 1 other identifier: IRB00298999
• Study Type: interventional
• Target: 1,000
• Locations: 4 countries
• Sites: 4

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.

Conditions

HIV Seropositivity; Tuberculosis; Household Contact

Keywords

Tuberculosis preventive treatment; rifapentine; HIV uninfected

Outcome Measures

Primary Outcomes (5)

• Treatment adherence- self-report

  Completion of TPT with \>90% adherence documented by self-report (both groups, Arms A and B)

  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

• Treatment adherence- pill count

  Completion of TPT with \>90% adherence documented by pill count (both groups, Arms A and B)

  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

• Treatment adherence- electronic monitoring device (EMD)

  Completion of TPT with \>90% adherence documented by pill count (both groups, Arms A and B)

  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

• Adverse Events

  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.

  from study entry at Day 0 through Month 6 (Week 24), to be reported at end of trial

• Early treatment discontinuation

  discontinuation of study medications because of side effects (both groups, Arms A and B)

  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

Secondary Outcomes (1)

• 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

Study Arms (2)

Group 1: People living with HIV infection without active TB

EXPERIMENTAL

Drug: Daily rifapentine and isoniazid for 4 weeks; Drug: Weekly rifapentine and isoniazid for 12 weeks

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

EXPERIMENTAL

Drug: Daily rifapentine and isoniazid for 4 weeks; Drug: Weekly rifapentine and isoniazid for 12 weeks

Interventions

Daily rifapentine and isoniazid for 4 weeks DRUG

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

Group 1: People living with HIV infection without active TB; Group 2: HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB

Weekly rifapentine and isoniazid for 12 weeks DRUG

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

Group 1: People living with HIV infection without active TB; Group 2: HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 13 years
• Weight \> 30 kg
• HIV-seropositive
• HIV viral load \<400 copies/mL, defined as "virally suppressed," on an EFV or DTG-based ART regimen (see Section 3.6.2)
• Candidates must meet WHO criteria for receiving TPT

You may not qualify if:

• 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)
• Likely to move from the study area during the study period
• Known recent exposure to a TB case with resistance to isoniazid or rifampicin.
• Previous treatment for active or latent TB for more than 30 days within the past 2 years
• On nevirapine, etravirine, rilpivirine, PI-based, or raltegravir-containing ART regimens
• Known sensitivity or intolerance to isoniazid or rifamycins
• Suspected acute hepatitis or known chronic or unstable liver disease\^
• ALT \> 3 times the upper limit of normal (ULN)
• Total bilirubin \> 2.5 times the ULN
• Pregnancy or breastfeeding Females of childbearing potential who are unable or unwilling to use two forms of contraception\*\*
• On prohibited medications (see Appendix I)
• Group 2: HIV-negative household contacts of an adult with confirmed pulmonary TB in Mozambique and Indonesia
• Age ≥ 13 years
• Weight \> 30 kg
• HIV-negative

Sponsors & Collaborators

• The Aurum Institute NPC: lead
• Johns Hopkins University: collaborator

Study Sites (4)

The Byramjee Jeejeebhoy Medical Centre (BJGMC-JHU) CRS

Pune, Maharashtra, 411001, India

Location

Yayasan KNCV - The Persahabatan Hospital, Jakarta

Jakarta, Jaya, 14350, Indonesia

Location

Fundação Aurum (The Aurum Institute Mozambique)

Chokwé, Gaza Province, Mozambique

Location

The Aurum Institute: Gavin J Churchyard Legacy Centre

Klerksdorp, North West, 2571, South Africa

Location

MeSH Terms

Conditions

HIV Seropositivity; Tuberculosis

Interventions

Isoniazid

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Gavin Churchyard

  Aurum Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomization list will be generated prior to starting enrolment using random block sizes that are stratified by HIV status \& country.

Study Record Dates

• First Submitted: October 26, 2021
• First Posted: November 12, 2021
• Study Start: July 19, 2023
• Primary Completion: July 11, 2025
• Study Completion: December 31, 2025
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1); MO (1); IN (1); ZA (1)