A pragmatic trial with an optimized dose of rifampicin and moxifloxacin for the treatment of drug-susceptible pulmonary tuberculosis: a study protocol for open-label, randomized phase III trial (OptiRiMoxTB)

Abstract

BACKGROUND: Current combination antibiotic treatment for drug-susceptible tuberculosis (DS-TB) usually takes 6 months to complete. This long duration can compromise clinical outcomes. Although a 4-month regimen including an optimized dose of rifapentine plus moxifloxacin is non-inferior to standard therapy, rifapentine is hard to source globally and adoption of this regimen has been slow. This trial investigates the efficacy and safety of a 4-month DS-TB treatment including the more readily available rifamycin, rifampicin 35 mg/kg, with or without moxifloxacin 400 mg. METHODS: This multi-centre phase III randomized open-label clinical trial will be conducted across four African countries (Gabon, Malawi, Mozambique and Tanzania). A total of 414 newly diagnosed consenting adult participants will be block randomized, after stratification by chest radiograph cavitation, to two experimental and one control arm at a ratio of 1:1:1. The first experimental group will receive optimized dose rifampicin (35 mg/kg) with routine weight-banded doses of isoniazid, pyrazinamide, and ethambutol once daily for 4 months. The second experimental group will receive optimized dose rifampicin (35 mg/kg) and moxifloxacin 400 mg once daily alongside routine doses of isoniazid and pyrazinamide. The control group will receive 6-month standard of care therapy: rifampicin (10 mg/kg) plus weight-banded dose of isoniazid, pyrazinamide, and ethambutol for 2 months, followed by the same doses of rifampicin and isoniazid for 4 months. Participants will be followed until the allocation of efficacy (TB-free survival) and safety (proportion of severe adverse events) outcomes. Secondary outcomes will also include the evaluation of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) for microbiological treatment monitoring. DISCUSSION: This study will evaluate whether 4-month duration multi-drug treatment including an optimized dose of rifampicin with or without moxifloxacin has non-inferior efficacy and safety outcomes compared to standard of care DS-TB therapy in Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT05575518. Registered on 10th October 2022.