OBJECTIVE: To compare the efficacy, safety and acceptability of two short-course regimens of isoniazid, rifampicin, pyrazinamide and ethambutol (HRZE) given either as fixed-dose combination (4-FDC) tablets or as single tablets (ST) in patients with newly diagnosed pulmonary tuberculosis (PTB). DESIGN: This randomised, open, multicentre, multinational study was conducted in 26 centres and included 1159 patients with smear-positive PTB. 4-FDC daily for 2 months then H+R for 4 months, or single preparations of H, R, Z and E for 2 months followed by H and R for 4 months were administered daily. Sputum smear conversion rates at 2, 4 and 6 months (end of treatment [EOT], primary endpoint) and at 9 and 12 months (follow-up) were measured, together with adverse events and the acceptability of the formulations. RESULTS:Smear conversion rates for 4-FDC and ST at EOT were 80.4% (468/582 patients) vs. 82.7% (477/577) in the intent-to-treat (ITT) population, and 98.1% (404/412) vs. 98.6% (416/422) in the per-protocol (PP) subgroup. Non-inferiority of 4-FDC was demonstrated at month 2, EOT and follow-up in both the ITT and the PP populations. Overall numbers of adverse events were not significantly different between the groups. CONCLUSION: The efficacy of the 4-FDC regimen was non-inferior to that of the ST regimens, but patient acceptability significantly improved with 4-FDC.
RCT Entities:
OBJECTIVE: To compare the efficacy, safety and acceptability of two short-course regimens of isoniazid, rifampicin, pyrazinamide and ethambutol (HRZE) given either as fixed-dose combination (4-FDC) tablets or as single tablets (ST) in patients with newly diagnosed pulmonary tuberculosis (PTB). DESIGN: This randomised, open, multicentre, multinational study was conducted in 26 centres and included 1159 patients with smear-positive PTB. 4-FDC daily for 2 months then H+R for 4 months, or single preparations of H, R, Z and E for 2 months followed by H and R for 4 months were administered daily. Sputum smear conversion rates at 2, 4 and 6 months (end of treatment [EOT], primary endpoint) and at 9 and 12 months (follow-up) were measured, together with adverse events and the acceptability of the formulations. RESULTS: Smear conversion rates for 4-FDC and ST at EOT were 80.4% (468/582 patients) vs. 82.7% (477/577) in the intent-to-treat (ITT) population, and 98.1% (404/412) vs. 98.6% (416/422) in the per-protocol (PP) subgroup. Non-inferiority of 4-FDC was demonstrated at month 2, EOT and follow-up in both the ITT and the PP populations. Overall numbers of adverse events were not significantly different between the groups. CONCLUSION: The efficacy of the 4-FDC regimen was non-inferior to that of the ST regimens, but patient acceptability significantly improved with 4-FDC.
Authors: Jennifer D Hosford; Michael E von Fricken; Michael Lauzardo; Myron Chang; Yunfeng Dai; Jennifer A Lyon; John Shuster; Kevin P Fennelly Journal: Tuberculosis (Edinb) Date: 2014-12-18 Impact factor: 3.131
Authors: Carmen R Gallardo; David Rigau Comas; Angélica Valderrama Rodríguez; Marta Roqué i Figuls; Lucy Anne Parker; Joan Caylà; Xavier Bonfill Cosp Journal: Cochrane Database Syst Rev Date: 2016-05-17
Authors: Abraham Aseffa; Joseph N Chukwu; Mahnaz Vahedi; Emmanuel N Aguwa; Ahmed Bedru; Tesfamariam Mebrahtu; Oliver C Ezechi; Getnet Yimer; Lawrence K Yamuah; Girmay Medhin; Cathy Connolly; Wasima Rida; Getachew Aderaye; Alimuddin I Zumla; Philip C Onyebujoh Journal: PLoS One Date: 2016-06-20 Impact factor: 3.240