Randomised controlled trial to evaluate the effectiveness of using the RD-1-based C-Tb skin test as a replacement for blood-based interferon-γ release assay for detection of, and initiation of preventive treatment for, tuberculosis infection: RID-TB:Dx study protocol

Introduction The predictive utility for incident tuberculosis (TB) of the purified protein derivative tuberculin skin test and region of difference 1 (RD1)-based interferon-gamma release assays (IGRA) is comparable; and either is recommended to test for latent TB infection (LTBI). Despite associated...

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Main Authors: Marc Lipman, Ibrahim Abubakar, Chris Griffiths, Penny Whiting, Robert Horne, Alex Ghanouni, Heinke Kunst, Mike Mandelbaum, Molebogeng X Rangaka, Karen Sanders, Peter J White, Angela Crook, Dominik Zenner, Trinh Duong, Vanessa Hack, Julian Surey, Yohhei Hamada, Henry Bern, Joanna Calvert, Marie Francis, Amy Louise Clarke, Ellen Owen-Powell, Helen L Booth
Format: Article
Language:English
Published: BMJ Publishing Group 2021-12-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/11/12/e050595.full
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author Marc Lipman
Ibrahim Abubakar
Chris Griffiths
Penny Whiting
Robert Horne
Alex Ghanouni
Heinke Kunst
Mike Mandelbaum
Molebogeng X Rangaka
Karen Sanders
Peter J White
Angela Crook
Dominik Zenner
Trinh Duong
Vanessa Hack
Julian Surey
Yohhei Hamada
Henry Bern
Joanna Calvert
Marie Francis
Amy Louise Clarke
Ellen Owen-Powell
Helen L Booth
author_facet Marc Lipman
Ibrahim Abubakar
Chris Griffiths
Penny Whiting
Robert Horne
Alex Ghanouni
Heinke Kunst
Mike Mandelbaum
Molebogeng X Rangaka
Karen Sanders
Peter J White
Angela Crook
Dominik Zenner
Trinh Duong
Vanessa Hack
Julian Surey
Yohhei Hamada
Henry Bern
Joanna Calvert
Marie Francis
Amy Louise Clarke
Ellen Owen-Powell
Helen L Booth
author_sort Marc Lipman
collection DOAJ
description Introduction The predictive utility for incident tuberculosis (TB) of the purified protein derivative tuberculin skin test and region of difference 1 (RD1)-based interferon-gamma release assays (IGRA) is comparable; and either is recommended to test for latent TB infection (LTBI). Despite associated high costs of IGRA, sites participating in LTBI screening in many high-income settings pragmatically favour IGRA due to its higher specificity and simpler logistics. A new RD1-based skin test, C-Tb, could offer an acceptable and as accurate, cheaper alternative to IGRA. Evaluating the impact of C-Tb on process and patient-related outcomes would provide important information to help guide its use in LTBI testing strategies.Methods and analysis This is a pragmatic multicentre, open-label, non-inferiority, randomised controlled trial. The trial will assess the initiation of LTBI treatment following a positive result of the randomised test as the primary outcome. Participants will be randomised to receive the C-Tb test (intervention) or IGRA (usual care, control) for initiation of treatment. We will enrol 1530 participants in England aged≥16 years who are eligible for LTBI testing and treatment according to UK guidance. In the C-Tb arm, skin induration will be assessed 2–3 days after intradermal injection and measured in millimetres of induration. Results of IGRA will be obtained in line with standard practice. Behavioural studies will explore people’s experiences, perspectives and preferences of LTBI testing and treatment. Economic analysis will estimate cost-effectiveness of changes to the diagnostic algorithm for LTBI. The protocol was developed with Patient and Public Involvement (PPI), which will continue throughout the trial.Ethics and dissemination Ethics approval has been obtained from The NHS Health Research Authority (269485). We will share results of the trial in peer-reviewed journals and conferences.Trial registration number EudraCT 2019-002592-34; ISRCTN17936038.
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spelling doaj-art-feec39c7a93341439aecf67ddde581fd2025-08-20T01:55:46ZengBMJ Publishing GroupBMJ Open2044-60552021-12-01111210.1136/bmjopen-2021-050595Randomised controlled trial to evaluate the effectiveness of using the RD-1-based C-Tb skin test as a replacement for blood-based interferon-γ release assay for detection of, and initiation of preventive treatment for, tuberculosis infection: RID-TB:Dx study protocolMarc Lipman0Ibrahim Abubakar1Chris Griffiths2Penny Whiting3Robert Horne4Alex Ghanouni5Heinke Kunst6Mike Mandelbaum7Molebogeng X Rangaka8Karen Sanders9Peter J White10Angela Crook11Dominik Zenner12Trinh Duong13Vanessa Hack14Julian Surey15Yohhei Hamada16Henry Bern17Joanna Calvert18Marie Francis19Amy Louise Clarke20Ellen Owen-Powell21Helen L Booth22Royal Free London Hospital NHS Foundation Trust, London, UKInstitute of Global Health, University College London, London, UKCentre for Primary Care and Public Health, Queen Mary University of London, London, UKassociate professor of clinical epidemiology7 UCL School of Pharmacy, University College London, London, UKCentre for Behavioural Medicine, UCL School of Pharmacy, London, UKBlizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UKTB Alert, London, UKInstitute for Global Health, University College London, London, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UKModelling and Economics Unit, Public Health England, London, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK13 Queen Mary University of London, London, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UKInstitute for Global Health, University College London, London, UKInstitute for Global Health, University College London, London, UKInstitute for Global Health, University College London, London, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UKInstitute for Global Health, University College London, London, UKCentre for Behavioural Medicine, UCL School of Pharmacy, London, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UKhonorary consultant thoracic physicianIntroduction The predictive utility for incident tuberculosis (TB) of the purified protein derivative tuberculin skin test and region of difference 1 (RD1)-based interferon-gamma release assays (IGRA) is comparable; and either is recommended to test for latent TB infection (LTBI). Despite associated high costs of IGRA, sites participating in LTBI screening in many high-income settings pragmatically favour IGRA due to its higher specificity and simpler logistics. A new RD1-based skin test, C-Tb, could offer an acceptable and as accurate, cheaper alternative to IGRA. Evaluating the impact of C-Tb on process and patient-related outcomes would provide important information to help guide its use in LTBI testing strategies.Methods and analysis This is a pragmatic multicentre, open-label, non-inferiority, randomised controlled trial. The trial will assess the initiation of LTBI treatment following a positive result of the randomised test as the primary outcome. Participants will be randomised to receive the C-Tb test (intervention) or IGRA (usual care, control) for initiation of treatment. We will enrol 1530 participants in England aged≥16 years who are eligible for LTBI testing and treatment according to UK guidance. In the C-Tb arm, skin induration will be assessed 2–3 days after intradermal injection and measured in millimetres of induration. Results of IGRA will be obtained in line with standard practice. Behavioural studies will explore people’s experiences, perspectives and preferences of LTBI testing and treatment. Economic analysis will estimate cost-effectiveness of changes to the diagnostic algorithm for LTBI. The protocol was developed with Patient and Public Involvement (PPI), which will continue throughout the trial.Ethics and dissemination Ethics approval has been obtained from The NHS Health Research Authority (269485). We will share results of the trial in peer-reviewed journals and conferences.Trial registration number EudraCT 2019-002592-34; ISRCTN17936038.https://bmjopen.bmj.com/content/11/12/e050595.full
spellingShingle Marc Lipman
Ibrahim Abubakar
Chris Griffiths
Penny Whiting
Robert Horne
Alex Ghanouni
Heinke Kunst
Mike Mandelbaum
Molebogeng X Rangaka
Karen Sanders
Peter J White
Angela Crook
Dominik Zenner
Trinh Duong
Vanessa Hack
Julian Surey
Yohhei Hamada
Henry Bern
Joanna Calvert
Marie Francis
Amy Louise Clarke
Ellen Owen-Powell
Helen L Booth
Randomised controlled trial to evaluate the effectiveness of using the RD-1-based C-Tb skin test as a replacement for blood-based interferon-γ release assay for detection of, and initiation of preventive treatment for, tuberculosis infection: RID-TB:Dx study protocol
BMJ Open
title Randomised controlled trial to evaluate the effectiveness of using the RD-1-based C-Tb skin test as a replacement for blood-based interferon-γ release assay for detection of, and initiation of preventive treatment for, tuberculosis infection: RID-TB:Dx study protocol
title_full Randomised controlled trial to evaluate the effectiveness of using the RD-1-based C-Tb skin test as a replacement for blood-based interferon-γ release assay for detection of, and initiation of preventive treatment for, tuberculosis infection: RID-TB:Dx study protocol
title_fullStr Randomised controlled trial to evaluate the effectiveness of using the RD-1-based C-Tb skin test as a replacement for blood-based interferon-γ release assay for detection of, and initiation of preventive treatment for, tuberculosis infection: RID-TB:Dx study protocol
title_full_unstemmed Randomised controlled trial to evaluate the effectiveness of using the RD-1-based C-Tb skin test as a replacement for blood-based interferon-γ release assay for detection of, and initiation of preventive treatment for, tuberculosis infection: RID-TB:Dx study protocol
title_short Randomised controlled trial to evaluate the effectiveness of using the RD-1-based C-Tb skin test as a replacement for blood-based interferon-γ release assay for detection of, and initiation of preventive treatment for, tuberculosis infection: RID-TB:Dx study protocol
title_sort randomised controlled trial to evaluate the effectiveness of using the rd 1 based c tb skin test as a replacement for blood based interferon γ release assay for detection of and initiation of preventive treatment for tuberculosis infection rid tb dx study protocol
url https://bmjopen.bmj.com/content/11/12/e050595.full
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