{
  "abstract": "Introduction 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.Methods and analysis 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.Ethics and dissemination 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.Trial registration number EUDRACT number: 2021-001626-22. CTIS: 2023-509075-17-00.",
  "authors": [
    {
      "affiliations": [
        "Clinical Microbiology Department, Consorcio Hospital General Universitario de Valencia, Valencia, Comunidad Valenciana, Spain",
        "Mycobacteria Study Group, Spanish Society of Infectious Diseases and Clinical Microbiology (GEIM-SEIMC), Spain, Spain"
      ],
      "name": "Laura Diab Casares"
    },
    {
      "affiliations": [
        "Mycobacteria Study Group, Spanish Society of Infectious Diseases and Clinical Microbiology (GEIM-SEIMC), Spain, Spain",
        "Infectious Diseases Department, Hospital Universitario Vall d'Hebron, Barcelona, Cataluña, Spain",
        "Networked Biomedical Research Center for Infectious Diseases (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain"
      ],
      "name": "Juan Espinosa Pereiro"
    },
    {
      "affiliations": [
        "Mycobacteria Study Group, Spanish Society of Infectious Diseases and Clinical Microbiology (GEIM-SEIMC), Spain, Spain",
        "Networked Biomedical Research Center for Infectious Diseases (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain",
        "Microbiology Department, Autonomous University of Barcelona, Medicine Department, Campus Hospital Universitario Vall d'Hebron, Barcelona, Cataluña, Spain"
      ],
      "name": "María Teresa Tórtola Fernández"
    },
    {
      "affiliations": [
        "Respiratory Department, Serveis Clinics SAU, Barcelona, Cataluña, Spain",
        "Respiratory Infections Working Group of the Catalan Society of Respiratory Medicine (SOCAP), Cataluña, Cataluña"
      ],
      "name": "Xavier Casas García"
    },
    {
      "affiliations": [
        "Epidemiology, Public Health Agency of Catalonia, Barcelona, Cataluña, Spain",
        "CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain"
      ],
      "name": "Joan Pau Millet"
    },
    {
      "affiliations": [
        "Infectious Diseases Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Cataluña, Spain"
      ],
      "name": "Virginia Pomar Solchaga"
    },
    {
      "affiliations": [
        "Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain"
      ],
      "name": "Enrique Navas Elorza"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Hospital Universitario Infanta Leonor, Madrid, Spain"
      ],
      "name": "Jesús Troya García"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain"
      ],
      "name": "Alberto Díaz de Santiago"
    },
    {
      "affiliations": [
        "Infectious Diseases Department, Hospital Universitario Virgen del Rocío, Sevilla, Andalucía, Spain"
      ],
      "name": "Rafael Luque Márquez"
    },
    {
      "affiliations": [
        "Medical–Surgical Unit for Respiratory Diseases (UMQER), Hospital Universitario Virgen del Rocío, Sevilla, Andalucía, Spain",
        "Integrated Research Program on Tuberculosis and Nontuberculous Mycobacteria (PII-TB&MNT), Spanish Society of Respiratory Medicine and Thoracic Surgery (SEPAR), Spain"
      ],
      "name": "Juan Francisco Medina Gallardo"
    },
    {
      "affiliations": [
        "Mycobacteria Study Group, Spanish Society of Infectious Diseases and Clinical Microbiology (GEIM-SEIMC), Spain, Spain",
        "Clinical Unit of Infectious Diseases, Microbiology and Clinical Parasitology (UCEIMP), Hospital Universitario Virgen del Rocío, Sevilla, Spain",
        "Seville Institute of Biomedicine, Sevilla, Andalucía, Spain"
      ],
      "name": "Verónica González Galán"
    },
    {
      "affiliations": [
        "Infectious Diseases Department, Hospital Universitario y Politecnico La Fe, Valencia, Spain"
      ],
      "name": "Marta Montero Alonso"
    },
    {
      "affiliations": [
        "Microbiology Department, Hospital Universitario y Politecnico La Fe, Valencia, Spain"
      ],
      "name": "Ana Gil Brusola"
    },
    {
      "affiliations": [
        "Mycobacteria Study Group, Spanish Society of Infectious Diseases and Clinical Microbiology (GEIM-SEIMC), Spain, Spain",
        "Department of Internal Medicine, Hospital Universitario Lucus Augusti, Lugo, Spain"
      ],
      "name": "Ramón Rabuñal Rey"
    },
    {
      "affiliations": [
        "Tuberculosis Unit, Infectious Diseases, Internal Medicine Department, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Galicia, Spain",
        "Immunology Research Group, Research Institute, Sanitaria Galicia Sur, Santiago de Compostela, Spain"
      ],
      "name": "Luis Anibarro García"
    },
    {
      "affiliations": [
        "Respiratory Department, Consorcio Hospital General Universitario de Valencia, Valencia, Comunidad Valenciana, Spain"
      ],
      "name": "Francisco Sanz Herrero"
    },
    {
      "affiliations": [
        "Clinical Microbiology Department, Consorcio Hospital General Universitario de Valencia, Valencia, Comunidad Valenciana, Spain",
        "Mycobacteria Study Group, Spanish Society of Infectious Diseases and Clinical Microbiology (GEIM-SEIMC), Spain, Spain",
        "Clinical Microbiology Department, Faculty of Medicine, University of Valencia, Valencia, Spain"
      ],
      "name": "Remedio Guna Serrano"
    },
    {
      "affiliations": [
        "Clinical Microbiology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain",
        "Sant Pau Biomedical Research Institute, Barcelona, Cataluña, Spain",
        "Department of Genetics and Microbiology, Autonomous University of Barcelona, Barcelona, Cataluña, Spain"
      ],
      "name": "Montserrat Garrigó Fullola"
    },
    {
      "affiliations": [
        "Clinical Microbiology Department, Hospital Universitario Ramon y Cajal, Madrid, Madrid, Spain"
      ],
      "name": "Marta Tato Díez"
    },
    {
      "affiliations": [
        "Clinical Microbiology Department, Hospital Universitario Infanta Leonor, Madrid, Spain"
      ],
      "name": "Tamar Talavan Zanón"
    },
    {
      "affiliations": [
        "Clinical Microbiology Department, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain"
      ],
      "name": "Maria Francisca Portero"
    },
    {
      "affiliations": [
        "Clinical Microbiology Department, Hospital Universitario Lucus Augusti, Lugo, Galicia, Spain"
      ],
      "name": "Pilar Alonso García"
    },
    {
      "affiliations": [
        "Clinical Microbiology Department, Hospital Provincial de Pontevedra, Pontevedra, Galicia, Spain"
      ],
      "name": "Ana M Saez López"
    },
    {
      "affiliations": [
        "Mycobacteria Study Group, Spanish Society of Infectious Diseases and Clinical Microbiology (GEIM-SEIMC), Spain, Spain",
        "Infectious Diseases Department, Hospital Universitario Vall d'Hebron, Barcelona, Cataluña, Spain",
        "Networked Biomedical Research Center for Infectious Diseases (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain"
      ],
      "name": "María Luisa Aznar"
    },
    {
      "affiliations": [
        "Infectious Diseases Department, Hospital Universitario Vall d'Hebron, Barcelona, Cataluña, Spain",
        "Networked Biomedical Research Center for Infectious Diseases (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain"
      ],
      "name": "Joan Martínez Campreciós"
    },
    {
      "affiliations": [
        "Infectious Diseases Department, Hospital Universitario Vall d'Hebron, Barcelona, Cataluña, Spain"
      ],
      "name": "Núria Saborit"
    },
    {
      "affiliations": [
        "Mycobacteria Study Group, Spanish Society of Infectious Diseases and Clinical Microbiology (GEIM-SEIMC), Spain, Spain",
        "Infectious Diseases Department, Hospital Universitario Vall d'Hebron, Barcelona, Cataluña, Spain",
        "Networked Biomedical Research Center for Infectious Diseases (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain"
      ],
      "name": "Adrián Sánchez Montalvá"
    }
  ],
  "title": "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",
  "uid": "aa5ed880-90a1-568e-bb46-5e97d28e749f"
}