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

Molebogeng X. Rangaka*, Yohhei Hamada, Trinh Duong, Henry Bern, Joanna Calvert, Marie Francis, Amy Louise Clarke, Alex Ghanouni, Vanessa Hack, Ellen Owen-Powell, Julian Surey, Karen Sanders, Helen L. Booth, Angela Crook, Chris Griffiths, Robert Horne, Heinke Kunst, Marc Lipman, Mike Mandelbaum, Peter J. WhitePenny Whiting, Dominik Zenner, Ibrahim Abubakar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

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.

Original languageEnglish
Article numbere050595
JournalBMJ Open
Volume11
Issue number12
DOIs
Publication statusPublished - 30 Dec 2021
Externally publishedYes

Bibliographical note

Funding Information: The protocol reported in this publication was supported by the National Institute for Health Research (NIHR) (RP-PG-0217-20009) and will receive support from the NIHR Clinical Research Network. Additional funding for patient and public involvement was provided by the UCLH/UCL Biomedical Research Centre Patient & Public Involvement bursary fund.

Open Access: This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

Publisher Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Citation: Rangaka MX, Hamada Y, Duong T, et al. 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 2021;11:e050595.

DOI: 10.1136/bmjopen-2021-050595

Keywords

  • clinical trials
  • diagnostic microbiology
  • preventive medicine
  • tuberculosis

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