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)
Primary Purpose
HIV Seropositivity, Tuberculosis, Household Contact
Status
Not yet recruiting
Phase
Phase 4
Locations
South Africa
Study Type
Interventional
Intervention
Daily rifapentine and isoniazid for 4 weeks
Weekly rifapentine and isoniazid for 12 weeks
Sponsored by
About this trial
This is an interventional prevention trial for HIV Seropositivity focused on measuring Tuberculosis preventive treatment, rifapentine, HIV uninfected
Eligibility 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
Sites / Locations
- The Aurum Institute: Gavin J Churchyard Legacy Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Group 1: People living with HIV infection without active TB
Group 2: HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB
Arm Description
Outcomes
Primary Outcome Measures
Treatment adherence- self-report
Completion of TPT with >90% adherence documented by self-report (both groups, Arms A and B)
Treatment adherence- pill count
Completion of TPT with >90% adherence documented by pill count (both groups, Arms A and B)
Treatment adherence- electronic monitoring device (EMD)
Completion of TPT with >90% adherence documented by pill count (both groups, Arms A and B)
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.
Early treatment discontinuation
discontinuation of study medications because of side effects (both groups, Arms A and B)
Secondary Outcome Measures
Cost-effectiveness
Incremental cost-effectiveness of 1HP and 3HP (compared to each other, ^ months of isoniazid (6H), and no treatment) using a societal perspective.
Full Information
NCT ID
NCT05118490
First Posted
October 26, 2021
Last Updated
January 31, 2023
Sponsor
The Aurum Institute NPC
Collaborators
Johns Hopkins University
1. Study Identification
Unique Protocol Identification Number
NCT05118490
Brief Title
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
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2023 (Anticipated)
Primary Completion Date
October 28, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Aurum Institute NPC
Collaborators
Johns Hopkins University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Seropositivity, Tuberculosis, Household Contact
Keywords
Tuberculosis preventive treatment, rifapentine, HIV uninfected
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
A randomization list will be generated prior to starting enrolment using random block sizes that are stratified by HIV status & country.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1000 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group 1: People living with HIV infection without active TB
Arm Type
Experimental
Arm Title
Group 2: HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Daily rifapentine and isoniazid for 4 weeks
Intervention Description
Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP)
Intervention Type
Drug
Intervention Name(s)
Weekly rifapentine and isoniazid for 12 weeks
Intervention Description
Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP)
Primary Outcome Measure Information:
Title
Treatment adherence- self-report
Description
Completion of TPT with >90% adherence documented by self-report (both groups, Arms A and B)
Time Frame
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
Title
Treatment adherence- pill count
Description
Completion of TPT with >90% adherence documented by pill count (both groups, Arms A and B)
Time Frame
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
Title
Treatment adherence- electronic monitoring device (EMD)
Description
Completion of TPT with >90% adherence documented by pill count (both groups, Arms A and B)
Time Frame
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
Title
Adverse Events
Description
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.
Time Frame
from study entry at Day 0 through Month 6 (Week 24), to be reported at end of trial
Title
Early treatment discontinuation
Description
discontinuation of study medications because of side effects (both groups, Arms A and B)
Time Frame
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 Outcome Measure Information:
Title
Cost-effectiveness
Description
Incremental cost-effectiveness of 1HP and 3HP (compared to each other, ^ months of isoniazid (6H), and no treatment) using a societal perspective.
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jayajothi Moodley
Phone
+27826593766
Email
JMoodley@auruminstitute.org
First Name & Middle Initial & Last Name or Official Title & Degree
Richard Chaisson
Email
rchaiss@jhmi.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gavin Churchyard
Organizational Affiliation
Aurum Institute
Official's Role
Study Chair
Facility Information:
Facility Name
The Aurum Institute: Gavin J Churchyard Legacy Centre
City
Klerksdorp
State/Province
North West Province
ZIP/Postal Code
2571
Country
South Africa
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr James Craig Innes
Phone
+27823369626
Email
cinnes@auruminstitute.org
First Name & Middle Initial & Last Name & Degree
Jayajothi Moodley
Phone
+27826593766
Email
JMoodley@auruminstitute.org
First Name & Middle Initial & Last Name & Degree
Oteng Letlape
First Name & Middle Initial & Last Name & Degree
Mgcini Moyo
First Name & Middle Initial & Last Name & Degree
Raesibe Agnes Pearl Selepe
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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
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