Tuberculosis Clinical Trial
— CORTISOfficial title:
A Randomized, Partially-blinded, Clinical Trial of Isoniazid and Rifapentine (3HP) Therapy to Prevent Pulmonary Tuberculosis in High-risk Individuals Identified by a Transcriptomic Correlate of Risk
Verified date | December 2018 |
Source | University of Cape Town |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Effective tuberculosis (TB) control requires that people who progress from latent
Mycobacterium tuberculosis (MTB) infection (LTBI) to TB disease are identified and treated
before they infect others. A prognostic correlate of risk (COR), based on messenger
ribonucleic acid (mRNA) expression signatures, which prospectively discriminates between TB
cases and healthy controls, has been constructed and validated. Based on published microarray
case-control datasets, the COR has 87% diagnostic sensitivity and 97% specificity for
prevalent TB disease; and in two nested case-control studies, 70% prognostic sensitivity and
84% specificity for incident TB disease occurring within one year of sampling (HIV uninfected
persons). Diagnostic and prognostic performance of the COR has not yet been tested in a
prospective cohort.
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).
Status | Active, not recruiting |
Enrollment | 2927 |
Est. completion date | December 31, 2019 |
Est. primary completion date | December 31, 2019 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 60 Years |
Eligibility |
Inclusion Criteria: 1. Written informed consent 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: 1. HIV infection 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 |
Country | Name | City | State |
---|---|---|---|
South Africa | Stellenbosch Immunology Research Group | Cape Town | Western Cape |
South Africa | Centre for the Aids Programme of Research in South Africa (CAPRISA) | Durban | KwaZulu-Natal |
South Africa | Aurum Institute | Klerksdorp | North West Province |
South Africa | Aurum Institute | Rustenburg | North West |
South Africa | South African Tuberculosis Vaccine Initiative (SATVI) | Worcester | Western Cape |
Lead Sponsor | Collaborator |
---|---|
University of Cape Town | Aurum Institute, Centre for the AIDS Programme of Research in South Africa, Fred Hutchinson Cancer Research Center, London School of Hygiene and Tropical Medicine, South African Tuberculosis Vaccine Initiative, University of Stellenbosch |
South Africa,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Treatment Efficacy | Treatment efficacy (TE) will be evaluated by comparing the incidence of endpoint-defined TB disease over 15 months in treated COR+ versus untreated COR+ participants. | 15 months | |
Primary | Performance of COR | The performance of the COR will be evaluated by comparing the cumulative incidence of endpoint-defined TB disease over 15 months in untreated COR+ versus untreated COR- participants | 15 months |
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