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 (1 to 3)

The Aurum Institute NPC

Status and phase

Enrolling

Phase 4

Conditions

Tuberculosis

Household Contact

HIV Seropositivity

Treatments

Drug: Daily rifapentine and isoniazid for 4 weeks

Drug: Weekly rifapentine and isoniazid for 12 weeks

Study type

Interventional

Funder types

Other

Identifiers

NCT05118490

IRB00298999

Details and patient eligibility

About

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.

Full 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).

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).

Enrollment

1,000 estimated patients

Sex

All

Ages

13+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Group 1: HIV-positive adolescents and adults in South Africa and India

Inclusion criteria:

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

Exclusion criteria:

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

Inclusion criteria:

Age ≥ 13 years
Weight > 30 kg
HIV-negative
Household contact of an adult with confirmed rifampicin-sensitive pulmonary TB
Candidates must meet WHO criteria for receiving TPT

Exclusion criteria:

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 exposure to TB cases with resistance to isoniazid or rifampicin in the source case
Previous treatment for active or latent TB for >30 days within the past 2 years
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