4‐month moxifloxacin containing regimens in the treatment of patients with sputum‐positive pulmonary tuberculosis in South India – a randomised clinical trial

Abstract Background Shortening tuberculosis (TB) treatment duration is a research priority. We tested the efficacy and safety of 3‐ and 4‐month regimens containing moxifloxacin in a randomised clinical trial in pulmonary TB (PTB) patients in South India. Methods New, sputum‐positive, adult, HIV‐negative, non‐diabetic PTB patients were randomised to 3‐ or 4‐month moxifloxacin regimens [moxifloxacin (M), isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E)] or to a control regimen (2H 3 R 3 Z 3 E 3 /4R 3 H 3 ) [C]. The 4 test regimens were 3R 7 H 7 Z 7 E 7 M 7 [M3], 2R 7 H 7 Z 7 E 7 M 7 /2R 7 H 7 M 7 [M4], 2R 7 H 7 Z 7 E 7 M 7 /2R 3 H 3 M 3 [M4‐I] or 2R 7 H 7 Z 7 E 7 M 7 /2R 3 H 3 E 3 M 3 [M4‐IE]. Treatment was directly observed. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post‐treatment. The primary end point was TB recurrence post‐treatment. Results Of 1371 patients, randomised, modified intention‐to‐treat (ITT) analysis was done in 1329 and per‐protocol (PP) analysis in 1223 patients. Regimen M3 was terminated due to high TB recurrence rates. ‘Favourable’ response at end of treatment was 96–100% in the moxifloxacin regimens and 93% in the control regimen. Among these, the TB recurrence occurred in 4.1% in the M4 regimen and in 4.5% in the control regimen and demonstrated equivalence within a 5% margin (95% CI −3.68, 4.55). Similar findings were observed in modified ITT analysis. The TB recurrence rates in the M4‐I and M4‐IE regimens did not show equivalence with the control regimen. Sixteen (1.4%) of 1087 patients in the moxifloxacin regimens required treatment modification. Conclusion The 4‐month daily moxifloxacin regimen [M4] was found to be equivalent and as safe as the 6‐month thrice‐weekly control regimen.