The Correlate of Risk Targeted Intervention Study

Tuberculosis Clinical Trial

— CORTIS  

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02735590
• Other study ID #: CORTIS-01
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: September 20, 2016
• Est. completion date: December 31, 2019

Study information

• Verified date: December 2018
• Source: University of Cape Town
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• 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

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Drug:
• 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.

Locations

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

Sponsors (7)

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

Country where clinical trial is conducted

South Africa, 

Outcome

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