HIV Seropositivity, Household Contact, Tuberculosis
Conditions
Keywords
Tuberculosis preventive treatment, rifapentine, HIV uninfected
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.
Interventions
DRUGDaily rifapentine and isoniazid for 4 weeks
Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP)
DRUGWeekly rifapentine and isoniazid for 12 weeks
Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP)
Sponsors
Johns Hopkins University
The Aurum Institute NPC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
A randomization list will be generated prior to starting enrolment using random block sizes that are stratified by HIV status & country.
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Group 1: HIV-positive adolescents and adults in South Africa and India 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
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 Inclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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) |
| 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. |
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
India, Indonesia, Mozambique, South Africa
Outcome results
None listed