NCT02581527.

Trial name or title	An international multi‐centre controlled clinical trial to evaluate 1200 mg and 1800 mg rifampicin daily in the reduction of treatment duration for pulmonary tuberculosis from 6 months to 4 months (RIFASHORT)
Methods	Study type: interventional, phase 3; study design: open‐label 3‐arm trial
Participants	Inclusion criteria: Patients with: Newly diagnosed, smear microscopy positive, pulmonary tuberculosis, rifampicin‐susceptible MTBC confirmed by Xpert MTB/RIF OR Smear microscopy negative, suspected pulmonary tuberculosis, confirmed by Xpert MTB/RIF as sputum MTBC positive and rifampicin susceptible No more than 1 week of previous treatment for tuberculosis, for active TB or confirmed or presumed latent TB infection ≥ 18 years old Consent to participation in the trial and to HIV testing Provide informed consent Stable home address within easy reach of the treatment facility and likely to remain there for the entire treatment and follow‐up period Women who are pre‐menopausal or of childbearing age must be using a barrier form of contraception (condoms, diaphragms, cervical caps, or contraceptive sponges), or must be surgically sterilized or have an intrauterine coil device (IUCD) in place for the duration of the treatment phase; alternatively they should agree to abstain from sexual activity during the treatment phase. Exclusion criteria: Rifampicin resistance identified by Xpert MTB/RIF or by direct susceptibility testing (late exclusions) Moribund phase TB meningitis or extrapulmonary TB Female and known to be pregnant or breastfeeding Condition likely to lead to uncooperative behaviour such as psychiatric illness or alcoholism History of seizures Contraindications to any medications in the study regimens HIV positive according to local testing algorithm Blood disorder (including grade 4 or above thrombocytopenia) Haemoglobin < 7 g/dL Peripheral neuritis Pre‐existing liver disease ALT > 5 times upper limit of normal (ULN) for that laboratory Raised bilirubin (grade 4 or above) Kidney disease Estimated creatinine clearance < 30 mL/min Previously diagnosed diabetes mellitus (non‐insulin‐dependent or insulin‐dependent) HbA1c > 48 mmol/mol Weight < 35 kg Taking any of the excluded medications listed in the Summary of Product Characteristics (SmPC) for any trial drugs Pre‐existing non‐tuberculous disease likely to prejudice response to, or assessment of, treatment as judged by the Principal Investigator Anticipated sample size: 654
Interventions	Interventions: 4‐month regimens Rifampicin 1200 mg combination ATT regimen 2 months of daily ethambutol, isoniazid, rifampicin, and pyrazinamide, followed by 2 months of daily isoniazid and rifampicin Supplement of 450 mg (weight bands 35 to 39 kg and 40 to 54 kg) or 600 mg (weight band 55 to 69 kg and 70 and more kg) of rifampicin will be given throughout the 4 months (2EHR 1200Z/2HR1200) Rifampicin 1800 mg combination ATT regimen 2 months of daily ethambutol, isoniazid, rifampicin, and pyrazinamide, followed by 2 months of daily isoniazid and rifampicin Supplement of 450 mg (weight bands 35 to 39 kg and 40 to 54 kg) or 600 mg (weight band 55 to 69 kg and 70 and more kg) of rifampicin will be given throughout the 4 months (2EHR1800Z/2HR1800) Control: Standard 6‐month ATT regimen 2 months of the standard regimen of isoniazid, pyrazinamide, and ethambutol plus 10 mg/kg rifampicin for the initial 8 weeks, followed by 4 months of isoniazid and rifampicin (at the same dose size) for an additional 4 months (2HRZE/4HR).
Outcomes	Primary outcomes: Efficacy: proportion with a combined unfavourable endpoint measured 18 months from randomization; this endpoint includes failure at end of treatment, recurrence, and death. This will be measured in the modified intent‐to‐treat microscopy positive population Safety: occurrence of grade 3 or 4 adverse events at any time during chemotherapy and 1 month post therapy in the intent‐to‐treat population with an MTBC positive test result Xpert MTB/RIF positive population Secondary outcomes Per‐protocol analysis of the primary efficacy outcome Combined unfavourable endpoint measured 18 months from randomization in the Xpert MTB/RIF positive (i) modified intent‐to‐treat and (ii) per‐protocol populations Sputum cultures positive for M tuberculosis at 8 and 12 weeks from randomization Any adverse event, up to 1 month after end of treatment, graded according to DAIDS criteria Time to unfavourable outcome in the modified to intent‐to‐treat and per‐protocol microscopy positive population
Starting date	March 2017; estimated study completion date: December 2020; status: recruiting
Contact information	Eduardo Rómulo Chávez Ticona. Calle Rio Huaura Nro. 319, Pueblo Libre, Lima, Peru Pueblo Libre Lima LIMA Perú. Ph: 993560268; Email: eticonacrg@gmail.com
Notes	Study locations: Bolivia, Botswana, Peru, Uganda Registration number:NCT02581527 Primary sponsor: St Georges University of London