TuberculosisPhase 2/3CORTISNCT02735590
The Correlate of Risk Targeted Intervention Study
A Phase 2/3 study testing Isoniazid and Rifapentine in people with Tuberculosis, run by University of Cape Town at 5 sites in South Africa.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Isoniazid and Rifapentine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,927 participants
- Where
- 5 sitesSouth Africa
- Study dates
- 20 Sep 2016to 31 Dec 2019
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Written informed consent
- Aged ≥18 and <60 years
- Known COR status (- or +)
- Known HIV status
- 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.
- Likely to remain in follow-up and adhere to protocol requirements
Who cannot join
- HIV infection
- Pregnant or lactating
- Diagnosed with TB disease within last 3 years
- Household exposure to a TB patient with known multi-drug resistant (MDR-) TB disease within last 3 years
- Body weight <40kg
- Known allergy to INH or Rifamycins
- Receiving antiarrhythmic, antidepressant, antipsychotic, antihypertensive, anticonvulsant, anticoagulant, or (inhaled or oral) corticosteroid therapy
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
South Africa5 sites
Stellenbosch Immunology Research Group
Cape Town, Western Cape, 7505
Centre for the Aids Programme of Research in South Africa (CAPRISA)
Durban, KwaZulu-Natal, 4013
Aurum Institute
Klerksdorp, North West, 2571
Aurum Institute
Rustenburg, North West, 0300
South African Tuberculosis Vaccine Initiative (SATVI)
Worcester, Western Cape, 6850
About this study
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
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).
Read more
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
- Test whether preventive therapy (3HP) reduces the rate of incident TB disease, compared to standard of care (active surveillance), in COR+ persons.
- Test whether COR status differentiates persons with cumulative prevalent or incident TB disease from persons without TB disease.
Secondary Aims
- Estimate whether COR status differentiates persons at high risk for incident TB disease from persons at low risk for incident TB disease
- Compare prognostic performance of the COR for incident TB disease with Interferon-gamma release assay (IGRA).
- Conditions
- Tuberculosis
- Being tested
- Isoniazid, Rifapentine
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsoniazidDrug
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).
RifapentineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Open-label 3HP | Experimental | 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. Receives: Drug: Isoniazid; Drug: Rifapentine |
| Baseline Screening; Active Surveillance | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 15 months
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
Measured: 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2016 (estimated)
- Study start20 Sep 2016
- Primary completion31 Dec 2019 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2,927 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cape Town
- Sponsor type
- University, hospital or other
- Collaborators
- South African Tuberculosis Vaccine Initiative, Aurum Institute, Centre for the AIDS Programme of Research in South Africa, University of Stellenbosch, London School of Hygiene and Tropical Medicine, Fred Hutchinson Cancer Center
- Responsible party
- Principal investigator, Mark Hatherill, University of Cape Town
- Investigators
- Mark Hatherill, MD, FCP (SA), Principal investigator, South African Tuberculosis Vaccine Initiative
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02735590
- Sponsor's protocol ID
- CORTIS-01
- Acronym
- CORTIS
- Status last verified
- Dec 2018
- First submitted
- 6 Apr 2016
- Last updated
- 24 Dec 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Publications
Publications
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.
PubMed 33508224
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02735590
- Acronym / sponsor ID
- CORTIS / CORTIS-01
- Conditions
- Tuberculosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,927 participants (actual)
- Lead sponsor
- University of Cape TownUniversity, hospital or other
- Collaborators
- South African Tuberculosis Vaccine Initiative, Aurum Institute, Centre for the AIDS Programme of Research in South Africa, University of Stellenbosch, London School of Hygiene and Tropical Medicine, Fred Hutchinson Cancer Center
- Study start
- 20 Sep 2016 (actual)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 12 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Test whether preventive therapy (3HP) reduces the rate of incident TB disease, compared to standard of care (active surveillance), in COR+ persons.
- Test whether COR status differentiates persons with cumulative prevalent or incident TB disease from persons without TB disease.
Secondary Aims
- Estimate whether COR status differentiates persons at high risk for incident TB disease from persons at low risk for incident TB disease
- Compare prognostic performance of the COR for incident TB disease with Interferon-gamma release assay (IGRA).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Open-label 3HP | Experimental | Drug: Isoniazid, Drug: RifapentineParticipants 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. |
| Baseline Screening; Active Surveillance | No intervention | –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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Written informed consent
- Aged ≥18 and <60 years
- Known COR status (- or +)
- Known HIV status
- 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.
Key exclusion criteria (8 listed)
- HIV infection
- Pregnant or lactating
- Diagnosed with TB disease within last 3 years
- Household exposure to a TB patient with known multi-drug resistant (MDR-) TB disease within last 3 years
- Body weight <40kg
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IsoniazidParticipants 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). | Drug | Open-label 3HP |
| RifapentineRifapentine 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. | Drug | Open-label 3HP |
Primary outcome
Treatment Efficacy
Time frame: 15 months
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.
Performance of COR
Time frame: 15 months
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2018.
- Derived from this study: PubMed 33508224Scriba 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.
- Individual participant dataSharing planned: Yes. Publications
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Hatherill, MD, FCP (SA) principal investigator
South African Tuberculosis Vaccine Initiative
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Isoniazid and Rifapentine in people with Tuberculosis, run by University of Cape Town at 5 sites in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Efficacy (time frame: 15 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02735590, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2018.