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

Tuberculosis Clinical Trial

— 1 to 3  

Official title:

A Randomized Trial Comparing Treatment Completion of Daily Rifapentine & Isoniazid for One Month (1HP) To Weekly Rifapentine & Isoniazid For 3 Months (3HP) In Persons Living With HIV and in HIV-negative Household Contacts of Recently Diagnosed Tuberculosis Patients, The "One To Three" Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05118490
• Other study ID #: IRB00298999
• Status: Recruiting
• Phase: Phase 4
• Start date: July 19, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2024
• Source: The Aurum Institute NPC
• Contact: Jayajothi Moodley
• Phone: +27826593766
• Email: JMoodley[@]auruminstitute.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 31, 2024
• Est. primary completion date: October 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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

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 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

Related Conditions & MeSH terms

• HIV Seropositivity
• Tuberculosis

Intervention

Drug:
• Daily rifapentine and isoniazid for 4 weeks
Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP)
• Weekly rifapentine and isoniazid for 12 weeks
Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP)

Locations

Country	Name	City	State
India	The Byramjee Jeejeebhoy Medical Centre (BJGMC-JHU) CRS	Pune	Maharashtra
Indonesia	Yayasan KNCV - The Persahabatan Hospital, Jakarta	Jakarta	Jaya
Mozambique	Fundação Aurum (The Aurum Institute Mozambique)	Chokwé	Gaza
South Africa	The Aurum Institute: Gavin J Churchyard Legacy Centre	Klerksdorp	North West Province

Sponsors (2)

Lead Sponsor	Collaborator
The Aurum Institute NPC	Johns Hopkins University

Countries where clinical trial is conducted

India,  Indonesia,  Mozambique,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Cost-effectiveness	Incremental cost-effectiveness of 1HP and 3HP (compared to each other, ^ months of isoniazid (6H), and no treatment) using a societal perspective.	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