Journal Article Randomized Controlled Trial Ppublish 3 citations
PubMed: 40414233 DOI: 10.1016/S1473-3099(25)00151-3
Efficacy and safety of 8-week regimens for the treatment of rifampicin-susceptible pulmonary tuberculosis (TRUNCATE-TB): a prespecified exploratory analysis of a multi-arm, multi-stage, open-label, randomised controlled trial.
Lancet Infect Dis 25(10):1084-1096
Authors: Nicholas I Paton, Christopher Cousins, Intan P Sari, Erlina Burhan, Nan-Kai Ng, Victoria B Dalay, Celina Suresh, Tutik Kusmiati, Ka Lip Chew, Vincent M Balanag, Qingshu Lu, Rovina Ruslami, Irawaty Djaharuddin, Jani J R Sugiri, Rholine S Veto, Christine Sekaggya-Wiltshire, Anchalee Avihingsanon, Jitendra Kumar Saini, Padmasayee Papineni, Andrew J Nunn, Angela M Crook
Affiliations
- Infectious Diseases Translational Research Programme and Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.
- Infectious Diseases Translational Research Programme and Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
- National University Hospital, Singapore.
- Persahabatan Hospital, Jakarta, Indonesia.
- De La Salle Medical and Health Sciences Institute, Cavite, Philippines.
- Dr. Soetomo Hospital, Surabaya, Indonesia.
- Lung Centre of the Philippines, Quezon City, Philippines.
- Singapore Clinical Research Institute, Singapore; Fortrea Singapore, Singapore.
- Universitas Padjadjaran, Bandung, Indonesia.
- Dr Wahidin Sudirohusodo Hospital, Makassar, Indonesia.
- Saiful Anwar Hospital, Malang, Indonesia.
- Tropical Disease Foundation, Makati, Philippines.
- Infectious Diseases Institute, Makerere University, Kampala, Uganda.
- HIV-NAT, Thai Red Cross AIDS Research Centre and Centre of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
- National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India.
- Medical Research Council Clinical Trials Unit, University College London, London, UK.
Abstract
BACKGROUND
WHO recommends a 2-month optimal duration for new drug regimens for rifampicin-susceptible tuberculosis. We aimed to investigate the efficacy and safety of the 8-week regimens that were assessed as part of the TRUNCATE management strategy of the TRUNCATE-TB trial.
METHODS
TRUNCATE-TB was a multi-arm, multi-stage, open-label, randomised controlled trial in which participants aged 18-65 years with rifampicin-susceptible pulmonary tuberculosis were randomly assigned via a web-based system, using permuted blocks, to 24-week standard treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol) or the TRUNCATE management strategy comprising initial 8-week treatment, then post-treatment monitoring and re-treatment where needed. The four 8-week regimens comprised five drugs, modified from standard treatment: high-dose rifampicin and linezolid, or high-dose rifampicin and clofazimine, or bedaquiline and linezolid, all given with isoniazid, pyrazinamide, and ethambutol; and rifapentine, linezolid, and levofloxacin, given with isoniazid and pyrazinamide. Here, we report the efficacy (proportion with unfavourable outcome; and difference from standard treatment, assessed via Bayesian methods) and safety of the 8-week regimens, assessed in the intention-to-treat population. This prespecified exploratory analysis is distinct from the previously reported 96-week outcome of the strategy in which the regimens were deployed. This trial is registered with ClinicalTrials.gov (NCT03474198).
FINDINGS
Between March 21, 2018, and March 26, 2020, 675 participants (674 in the intention-to-treat population) were enrolled and randomly assigned to the standard treatment group or one of the four 8-week regimen groups. Two 8-week regimens progressed to full enrolment. An unfavourable outcome (mainly relapse) occurred in seven (4%) of 181 participants on standard treatment; 46 (25%) of 184 on the high-dose rifampicin and linezolid-containing regimen (adjusted difference 21·0%, 95% Bayesian credible interval [BCI] 14·3-28·1); and 26 (14%) of 189 on the bedaquiline and linezolid-containing regimen (adjusted difference 9·3% [4·3-14·9]). Grade 3-4 adverse events occurred in 24 (14%) of 181 participants on standard treatment, 20 (11%) of 184 on the rifampicin-linezolid regimen, and 22 (12%) of 189 on the bedaquiline-linezolid regimen.
INTERPRETATION
Efficacy was worse with 8-week regimens, although the difference from standard treatment varied between regimens. Even the best 8-week regimen (bedaquiline-linezolid) should only be used as part of a management strategy involving post-treatment monitoring and re-treatment if necessary.
FUNDING
Singapore National Medical Research Council; UK Department of Health and Social Care; UK Foreign, Commonwealth, and Development Office; UK Medical Research Council; Wellcome Trust; and UK Research and Innovation Medical Research Council.
MeSH
Ethambutol, Tuberculosis, Pulmonary, Safety, Pharmaceutical Preparations, Multiple Chronic Conditions, Linezolid, Tuberculosis, Therapeutics, Isoniazid, Communicable Diseases, Rifampin, Pyrazinamide