Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE2/PHASE3
2927 participants
INTERVENTIONAL
2016-09-20
2019-12-31
Brief Summary
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COR+ status is not directly associated with LTBI; and may, or may not, be amenable to preventive therapy. Although effective in the short-term, preventive therapy is not recommended for treatment of LTBI in HIV uninfected adults living in high TB burden countries, due to rapid loss of protection; and treatment burden. A 3-month, 12-dose, once-weekly preventive therapy regimen of high dose Isoniazid (INH) and Rifapentine (3HP) has been recommended as equivalent to 6 months of daily INH for treatment of LTBI in low TB burden countries by the World Health Organization (WHO).
A 'screen \& treat' strategy, based on serial mass campaigns to provide targeted, short-course preventive therapy only to COR+ persons at highest risk of TB disease, may offer the solution for durable, community-wide protection in high TB burden countries. The efficacy of 3HP for prevention of incident TB disease in COR+ persons has not yet been tested in a clinical trial.
Primary Aims
1. Test whether preventive therapy (3HP) reduces the rate of incident TB disease, compared to standard of care (active surveillance), in COR+ persons.
2. Test whether COR status differentiates persons with cumulative prevalent or incident TB disease from persons without TB disease.
Secondary Aims
1. Estimate whether COR status differentiates persons at high risk for incident TB disease from persons at low risk for incident TB disease
2. Compare prognostic performance of the COR for incident TB disease with Interferon-gamma release assay (IGRA).
Detailed Description
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Conditions
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Study Design
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RANDOMIZED
SINGLE_GROUP
PREVENTION
NONE
Study Groups
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Open-label 3HP
Participants in the Treatment Arm will receive high dose INH (15mg per kg body weight, rounded up to the nearest 100 mg; maximum dose 900 mg) with Pyridoxine supplementation (25mg), and Rifapentine based on body weight (\>32kg - 50kg: 750 mg; \>50kg: 900 mg), given weekly as 12 directly observed treatment (DOT) oral doses, ideally with food, over 3 months. Dispensing of IP and Directly Observed Treatment (DOT) field visits in Treatment Arm participants will be performed by staff members not involved in TB symptom screening or investigation. Participants receiving 3HP who develop symptoms of hepatotoxicity will be evaluated by an Investigator.
Isoniazid
Participants in the Treatment Arm will receive high dose Isoniazid - 15mg per kg body weight, rounded up to the nearest 100 mg; maximum dose 900 mg with Pyridoxine supplementation (25mg).
Rifapentine
Rifapentine based on body weight (\>32kg - 50kg: 750 mg; \>50kg: 900 mg), given weekly as 12 directly observed treatment (DOT) oral doses, ideally with food, over 3 months.
Baseline Screening; Active Surveillance
Adult volunteers living in TB hyperendemic communities of South Africa will be consented and screened. Individuals with HIV infection and conditions likely to affect the performance of the COR assay, or the safety and/or efficacy of the 3HP investigational regimen, will not be enrolled. Active surveillance for TB disease (Observation Arm), including regular symptom screening and symptom-targeted TB investigation (all participants) will be conducted on this Arm.
No interventions assigned to this group
Interventions
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Isoniazid
Participants in the Treatment Arm will receive high dose Isoniazid - 15mg per kg body weight, rounded up to the nearest 100 mg; maximum dose 900 mg with Pyridoxine supplementation (25mg).
Rifapentine
Rifapentine based on body weight (\>32kg - 50kg: 750 mg; \>50kg: 900 mg), given weekly as 12 directly observed treatment (DOT) oral doses, ideally with food, over 3 months.
Eligibility Criteria
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Inclusion Criteria
2. Aged ≥18 and \<60 years
3. Known COR status (- or +)
4. Known HIV status
5. Women of child-bearing potential who are not surgically sterilized must agree to practice adequate contraception (barrier method or non-hormonal intrauterine device, alone or in addition to systemic hormonal contraceptive method) or abstain from heterosexual intercourse during the first 3 months on study.
6. Likely to remain in follow-up and adhere to protocol requirements
Exclusion Criteria
2. Pregnant or lactating
3. Diagnosed with TB disease within last 3 years
4. Household exposure to a TB patient with known multi-drug resistant (MDR-) TB disease within last 3 years
5. Body weight \<40kg
6. Known allergy to INH or Rifamycins
7. Receiving antiarrhythmic, antidepressant, antipsychotic, antihypertensive, anticonvulsant, anticoagulant, or (inhaled or oral) corticosteroid therapy
8. Any medical, surgical, or other condition, including but not limited to known diabetes mellitus (requiring oral or injectable therapy), liver disease, porphyria, peripheral neuropathy, epilepsy, psychosis, or alcoholism, that in the opinion of the Investigator is likely to interfere with COR performance; safety and efficacy of the investigational products (IP); or adherence to protocol requirements
18 Years
60 Years
ALL
Yes
Sponsors
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South African Tuberculosis Vaccine Initiative
OTHER
Aurum Institute
OTHER
Centre for the AIDS Programme of Research in South Africa
NETWORK
University of Stellenbosch
OTHER
London School of Hygiene and Tropical Medicine
OTHER
Fred Hutchinson Cancer Center
OTHER
University of Cape Town
OTHER
Responsible Party
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Mark Hatherill
National Principal Investigator
Principal Investigators
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Mark Hatherill, MD, FCP (SA)
Role: PRINCIPAL_INVESTIGATOR
South African Tuberculosis Vaccine Initiative
Locations
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Centre for the Aids Programme of Research in South Africa (CAPRISA)
Durban, KwaZulu-Natal, South Africa
Aurum Institute
Klerksdorp, North West, South Africa
Aurum Institute
Rustenburg, North West, South Africa
Stellenbosch Immunology Research Group
Cape Town, Western Cape, South Africa
South African Tuberculosis Vaccine Initiative (SATVI)
Worcester, Western Cape, South Africa
Countries
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References
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Scriba TJ, Fiore-Gartland A, Penn-Nicholson A, Mulenga H, Kimbung Mbandi S, Borate B, Mendelsohn SC, Hadley K, Hikuam C, Kaskar M, Musvosvi M, Bilek N, Self S, Sumner T, White RG, Erasmus M, Jaxa L, Raphela R, Innes C, Brumskine W, Hiemstra A, Malherbe ST, Hassan-Moosa R, Tameris M, Walzl G, Naidoo K, Churchyard G, Hatherill M; CORTIS-01 Study Team. Biomarker-guided tuberculosis preventive therapy (CORTIS): a randomised controlled trial. Lancet Infect Dis. 2021 Mar;21(3):354-365. doi: 10.1016/S1473-3099(20)30914-2. Epub 2021 Jan 25.
Other Identifiers
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CORTIS-01
Identifier Type: -
Identifier Source: org_study_id