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

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 (2H3R3Z3E3/4R3H3) [C]. The 4 test regimens were 3R7H7Z7E7M7 [M3], 2R7H7Z7E7M7/2R7H7M7 [M4], 2R7H7Z7E7M7/2R3H3M3 [M4‐I] or 2R7H7Z7E7M7/2R3H3E3M3 [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. Contexte La réduction de la durée du traitement de la tuberculose (TB) est une priorité de recherche. Nous avons testé l'efficacité et la sécurité de schémas thérapeutiques contenant de la moxifloxacine pendant 3 et 4 mois dans un essai clinique randomisé chez des patients atteints de TB pulmonaire (PTB) dans le sud de l’Inde. Méthodes De nouveaux patients PTB, adultes, non diabétiques, positifs pour les expectorations, VIH négatifs ont été randomisés pour des schémas thérapeutiques contenant de la moxifloxacine pendant 3 mois ou 4 mois [moxifloxacine (M), isoniazide (H), rifampicine (R), pyrazinamide (Z), l'éthambutol (E)] ou pour un régime témoin (2H3R3Z3E3/4R3H3) [C]. Les 4 régimes de l’essai étaient 3R7H7Z7E7M7 [M3], 2R7H7Z7E7M7/2R7H7M7 [M4], 2R7H7Z7E7M7/