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)

Background Current combination antibiotic treatment for drug-susceptible tuberculosis (DS-TB) usually takes six months to complete. This long duration can compromise clinical outcomes. Although a four-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 four-month DS-TB treatment including the more readily available rifamycin, rifampicin 35mg/kg, with or without moxifloxacin 400mg. 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 (35mg/kg) with routine weight-banded doses of isoniazid, pyrazinamide, and ethambutol once daily for four-months. The second experimental group will receive optimized dose rifampicin (35mg/kg) and moxifloxacin 400mg once daily alongside routine doses of isoniazid and pyrazinamide. The control group will receive six-month standard of care therapy: rifampicin (10mg/kg) plus weight banded dose of isoniazid, pyrazinamide, and ethambutol for two months, followed by the same doses of rifampicin and isoniazid for four 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 four-month duration multi-drug treatment including an optimized dose of rifampicin with or without moxifloxacin have non-inferior efficacy and safety outcomes compared to standard of care DS-TB therapy in Africa. Trial registration: ClinicalTrials.gov, ID: NCT05575518 registered on 10th October 2022.