Journal Article

Multicentre controlled open randomised clinical trial to assess efficacy and safety of an anti-tuberculosis drug combination based on optimised-dose rifampicin, optimised-dose moxifloxacin and optimised-dose linezolid for TB: the RML-TB trial protocol

Talavan Zanón, Tamar, Troya García, Jesús, Rabuñal Rey, Ramón, Diab Casares, Laura, Alonso García, Pilar, Martínez Campreciós, Joan, Espinosa Pereiro, Juan, Tórtola Fernández, María Teresa, Díaz de Santiago, Alberto, Montero Alonso, Marta, Aznar, María Luisa, Saborit, Núria, Portero, Maria Francisca, Saez López, Ana M, Sanz Herrero, Francisco, Anibarro García, Luis, Luque Márquez, Rafael, Tato Díez, Marta, Guna Serrano, Remedio, Casas García, Xavier, Navas Elorza, Enrique, González Galán, Verónica, Garrigó Fullola, Montserrat, Medina Gallardo, Juan Francisco, Sánchez Montalvá, Adrián, Millet, Joan Pau, Gil Brusola, Ana, Pomar Solchaga, Virginia

2025

Overview

International organisations, scientists and the tuberculosis (TB) community have been advocating for a shorter, safer treatment for drug-susceptible (DS)-TB with equal or better efficacy than current regimens. A promising approach to achieve this is the combination of dose-optimised repurposed drugs. The RML-TB trial is a phase IIb, randomised, non-inferiority, controlled, open-label, multicentre clinical trial. It compares an experimental regimen (optimised-dose rifampicin (R) at 30mg/kg/day, moxifloxacin 600mg/day and linezolid (L) 600 mg/day) with the standard fixed-dose combination regimen of R, isoniazid, pyrazinamide and ethambutol. In the experimental arm, L is administered at 600 mg two times per day for 2 weeks, then once daily for 6 weeks. The primary efficacy outcome is the proportion of patients with negative culture at 8 weeks. Sputum samples will be collected at screening visit, randomisation visit and 1 week, 2 weeks, 4 weeks, 6 weeks and 8 weeks post randomisation. The primary safety outcome is the incidence of grade 3-4 adverse events or a change in treatment regimen within 8 weeks. Safety assessment will be done using the Common Terminology Criteria for Adverse Events classification version 5. Participants must be at least 18 years old, with smear-positive, DS pulmonary TB. Exclusion criteria include corrected QT interval (QTc) prolongation, HIV positive status, severely impaired blood counts or the use of QTc-prolonging drugs. The study will enrol 120 patients (60 per arm) over a 2.5-year period across 13 TB units in Spain. The study was approved by the ethics committee from Vall d'Hebron University Hospital on the meeting held on 18 March 2022 and The Spanish Drug Agency. Patients will provide informed consent and can withdraw from the trial at any time without giving any reason. This decision will not affect their medical care. Data collection is minimal, and analysis will be blinded. Personal data will be restricted to principal investigators or authorised personnel. Results will be shared via the European Union Drug Regulating Authorities Clinical Trials Database (EUDRACT) website and published in an open-source medical journal, guiding future TB clinical trials and treatment development. EUDRACT number: 2021-001626-22. CTIS: 2023-509075-17-00.

• Publisher: BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adult / Antitubercular Agents - administration & dosage / Antitubercular Agents - adverse effects / Clinical significance / Clinical trials / Clinical Trials, Phase II as Topic / Drug dosages / Drug resistance / Drug Therapy, Combination - methods / Equivalence Trials as Topic / Ethambutol - administration & dosage / Humans / Isoniazid - administration & dosage / Linezolid - administration & dosage / Linezolid - adverse effects / Moxifloxacin - administration & dosage / Moxifloxacin - adverse effects / Multicenter Studies as Topic / Patients / Pharmacokinetics / Pyrazinamide - administration & dosage / Quality of life / Questionnaires / Randomized Controlled Trials as Topic / Respiratory Research / Rifampin - administration & dosage / Rifampin - adverse effects / Standard of care / Toxicity / Treatment Outcome / Tuberculosis / Tuberculosis, Pulmonary - drug therapy