Evidence map›Paper›PMID 33508224›Full record

Trial reportThe Lancet. Infectious diseases2021

Biomarker-guided tuberculosis preventive therapy (CORTIS): a randomised controlled trial.

Thomas J Scriba, Andrew Fiore-Gartland, Adam Penn-Nicholson, Humphrey Mulenga, Stanley Kimbung Mbandi, Bhavesh Borate, Simon C Mendelsohn, Katie Hadley, Chris Hikuam, Masooda Kaskar and 19 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Infectious diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02735590 (A Randomized, Partially-blinded, Clinical Trial of Isoniazid and Rifapentine), which is not on this map. Cited by 88 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 7 pooled it
8.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02735590 phase2 / phase3unknown statusnot on this map

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

TypeinterventionalSponsorUniversity of Cape TownRan2016 to 2019Enrolled2,927ConditionsTuberculosisArmsIsoniazid, Rifapentine
3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 7 syntheses or guidelines pooled it, 145 citations in OpenAlex.

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  19. Peripheral cytokine distinguish recent fromFrontiers in microbiology · 2026
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28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 8 institutions in 3 countries.

Thomas J ScribaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Andrew Fiore-GartlandVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Adam Penn-NicholsonSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Humphrey MulengaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Stanley Kimbung MbandiSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Bhavesh BorateVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Simon C MendelsohnSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Katie HadleySouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Chris HikuamSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Masooda KaskarSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Munyaradzi MusvosviSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Nicole BilekSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Steven SelfVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Tom SumnerTB Modelling Group, TB Centre, Centre for Mathematical Modelling of Infectious Diseases, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
Richard G WhiteTB Modelling Group, TB Centre, Centre for Mathematical Modelling of Infectious Diseases, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
Mzwandile ErasmusSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Lungisa JaxaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Rodney RaphelaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Craig InnesThe Aurum Institute, Johannesburg, South Africa.
William BrumskineThe Aurum Institute, Johannesburg, South Africa.
Andriëtte HiemstraDST/NRF Centre of Excellence for Biomedical TB Research and South African Medical Research Council Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Parow, South Africa.
Stephanus T MalherbeDST/NRF Centre of Excellence for Biomedical TB Research and South African Medical Research Council Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Parow, South Africa.
Razia Hassan-MoosaCentre for the AIDS Programme of Research in South Africa (CAPRISA), Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
Michèle TamerisSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Gerhard WalzlDST/NRF Centre of Excellence for Biomedical TB Research and South African Medical Research Council Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Parow, South Africa.
Kogieleum NaidooCentre for the AIDS Programme of Research in South Africa (CAPRISA), Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
Gavin ChurchyardThe Aurum Institute, Johannesburg, South Africa; School of Public Health, University of Witwatersrand, Johannesburg, South Africa.
Mark HatherillSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa. Electronic address: mark.hatherill@uct.ac.za.
CORTIS-01 Study Team
University of Cape Town · ZASouth African Tuberculosis Vaccine Initiative · ZAFred Hutch Cancer Center · USAurum Institute · ZACentre for the AIDS Programme of Research in South Africa · ZALondon School of Hygiene & Tropical Medicine · GBSouth African Medical Research Council · ZAStellenbosch University · ZA

Funding

Aurum Clinical Trials UnitUM1AI154463 · NIAID · AURUM INSTITUTE NPC · PI Gavin John Churchyard · 2021 to 2026
$8.1M
NIAID NIH HHS UM1 AI154463
6 · The paper itself

Abstract

backgroundTargeted preventive therapy for individuals at highest risk of incident tuberculosis might impact the epidemic by interrupting transmission. We tested performance of a transcriptomic signature of tuberculosis (RISK11) and efficacy of signature-guided preventive therapy in parallel, using a hybrid three-group study design.

methodsAdult volunteers aged 18-59 years were recruited at five geographically distinct communities in South Africa. Whole blood was sampled for RISK11 by quantitative RT-PCR assay from eligible volunteers without HIV, recent previous tuberculosis (ie, <3 years before screening), or comorbidities at screening. RISK11-positive participants were block randomised (1:2; block size 15) to once-weekly, directly-observed, open-label isoniazid and rifapentine for 12 weeks (ie, RISK11 positive and 3HP positive), or no treatment (ie, RISK11 positive and 3HP negative). A subset of eligible RISK11-negative volunteers were randomly assigned to no treatment (ie, RISK11 negative and 3HP negative). Diagnostic discrimination of prevalent tuberculosis was tested in all participants at baseline. Thereafter, prognostic discrimination of incident tuberculosis was tested in the untreated RISK11-positive versus RISK11-negative groups, and treatment efficacy in the 3HP-treated versus untreated RISK11-positive groups, during active surveillance through 15 months. The primary endpoint was microbiologically confirmed pulmonary tuberculosis. The primary outcome measures were risk ratio [RR] for tuberculosis of RISK11-positive to RISK11-negative participants, and treatment efficacy. This trial is registered with ClinicalTrials.gov, NCT02735590.

findings20 207 volunteers were screened, and 2923 participants were enrolled, including RISK11-positive participants randomly assigned to 3HP (n=375) or no 3HP (n=764), and 1784 RISK11-negative participants. Cumulative probability of prevalent or incident tuberculosis disease was 0·066 (95% CI 0·049 to 0·084) in RISK11-positive (3HP negative) participants and 0·018 (0·011 to 0·025) in RISK11-negative participants (RR 3·69, 95% CI 2·25-6·05) over 15 months. Tuberculosis prevalence was 47 (4·1%) of 1139 versus 14 (0·78%) of 1984 in RISK11-positive compared with RISK11-negative participants, respectively (diagnostic RR 5·13, 95% CI 2·93 to 9·43). Tuberculosis incidence over 15 months was 2·09 (95% CI 0·97 to 3·19) vs 0·80 (0·30 to 1·30) per 100 person years in RISK11-positive (3HP-negative) participants compared with RISK11-negative participants (cumulative incidence ratio 2·6, 95% CI 1·2 to 5·9). Serious adverse events related to 3HP included one hospitalisation for seizures (unintentional isoniazid overdose) and one death of unknown cause (possibly temporally related). Tuberculosis incidence over 15 months was 1·94 (95% CI 0·35 to 3·50) versus 2·09 (95% CI 0·97 to 3·19) per 100 person-years in 3HP-treated RISK11-positive participants compared with untreated RISK11-positive participants (efficacy 7·0%, 95% CI -145 to 65).

interpretationThe RISK11 signature discriminated between individuals with prevalent tuberculosis, or progression to incident tuberculosis, and individuals who remained healthy, but provision of 3HP to signature-positive individuals after exclusion of baseline disease did not reduce progression to tuberculosis over 15 months.

fundingBill and Melinda Gates Foundation, South African Medical Research Council.

Indexed as

AdultAntitubercular AgentsBiomarkersDrug Administration ScheduleFemaleHIV SeronegativityHumansIncidenceIsoniazidMaleMycobacterium tuberculosisReverse Transcriptase Polymerase Chain ReactionRifampinRNA, BacterialSouth AfricaTreatment OutcomeAntitubercular AgentsBiomarkersIsoniazidRifampinrifapentineRNA, Bacterial

Identifiers

PMID33508224
PMCPMC7907670
OpenAlexW3121136345

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.