Four-month clofazimine regimen for susceptible pulmonary TB: a randomized clinical trial.

BACKGROUND: Clofazimine, an antimycobacterial agent, has demonstrated efficacy in reducing the treatment duration for MDR TB.

OBJECTIVES: To determine whether a 16 week clofazimine-based regimen is non-inferior to the standard 24 week regimen for drug-susceptible pulmonary TB.

METHODS: CORTAIL was a multicentric, investigator-initiated, randomized controlled trial designed to assess the non-inferiority of a 16 week clofazimine-based regimen compared with the standard 24 week regimen for drug-susceptible pulmonary TB (Clinical Trials Registry of India no. CTRI/2019/03/018102). In the intervention arm, clofazimine replaced ethambutol during both the intensive and continuation phases of treatment. The primary outcome was relapse at the end of 3 month follow-up after treatment completion.

RESULTS: Across 11 centres, a total of 161 patients were randomized to the standard regimen and 161 patients received the shorter regimen. Relapse was observed in 1.9% patients in the standard group and 3.2% in the shorter regimen, the difference lying within the predefined non-inferiority margin [relative risk (RR) 1.65; 95% CI 0.444-6.19; P = 0.723; adjusted risk (AR) 1.2%; 95% CI -3.3% to 6.1%]. Key secondary outcome of relapse at 1 year was also not significantly different between the two groups (RR 1.31; 95% CI 0.58-2.95; P = 0.652; AR 1.8%; 95% CI -4.5% to 8.2%). The proportion of patients achieving sputum smear negativity (RR 1.59; 95% CI 0.69-3; P = 0.36; AR 3.1%; 95% CI -3.2% to 9.5%) and bacteriological cure (RR 1.03; 95% CI 0.57-1.88; P = 0.99; AR 0.4%; 95% CI -7.4% to 8.2%) by the end of treatment was similar between the two treatment arms.

CONCLUSIONS: A clofazimine-based 16 week regimen was found to be safe and non-inferior to the currently available 24 week regimen.