SETTING: Tertiary care hospital in Kanpur, India. BACKGROUND: The need for a standardised treatment protocol for multidrug-resistant tuberculosis (MDR-TB) in resource-limited countries is being increasingly recognised. OBJECTIVE: To assess the effectiveness of high-dose isoniazid (INH) (16-18 mg/kg) adjuvant to second-line therapy in documented cases of MDR-TB. DESIGN: The present study is a double blind, randomised controlled trial with three treatment arms, high-dose INH, normal-dose INH and placebo, in addition to second-line drugs. Primary outcomes of the study were time to sputum culture conversion and proportion with sputum culture negative 6 months after treatment initiation. Secondary outcomes were radiological improvement at 1 year post treatment and development of toxicity. RESULTS: After adjustment for potential confounders, subjects who received high-dose INH became sputum-negative 2.38 times (95%CI 1.45-3.91, P = 0.001) more rapidly than those who did not receive it, and had a 2.37 times (95%CI 1.46-3.84, P < 0.001) higher likelihood of being sputum-negative at 6 months. These subjects showed significantly better radiological improvement without an increased risk of INH toxicity. CONCLUSION: In low-resource scenarios where a standardised therapeutic protocol is used for MDR-TB, the protocol can be significantly improved by including high-dose INH as an adjuvant.
RCT Entities:
SETTING: Tertiary care hospital in Kanpur, India. BACKGROUND: The need for a standardised treatment protocol for multidrug-resistant tuberculosis (MDR-TB) in resource-limited countries is being increasingly recognised. OBJECTIVE: To assess the effectiveness of high-dose isoniazid (INH) (16-18 mg/kg) adjuvant to second-line therapy in documented cases of MDR-TB. DESIGN: The present study is a double blind, randomised controlled trial with three treatment arms, high-dose INH, normal-dose INH and placebo, in addition to second-line drugs. Primary outcomes of the study were time to sputum culture conversion and proportion with sputum culture negative 6 months after treatment initiation. Secondary outcomes were radiological improvement at 1 year post treatment and development of toxicity. RESULTS: After adjustment for potential confounders, subjects who received high-dose INH became sputum-negative 2.38 times (95%CI 1.45-3.91, P = 0.001) more rapidly than those who did not receive it, and had a 2.37 times (95%CI 1.46-3.84, P < 0.001) higher likelihood of being sputum-negative at 6 months. These subjects showed significantly better radiological improvement without an increased risk of INH toxicity. CONCLUSION: In low-resource scenarios where a standardised therapeutic protocol is used for MDR-TB, the protocol can be significantly improved by including high-dose INH as an adjuvant.
Authors: V R Bollela; E I Namburete; C S Feliciano; D Macheque; L H Harrison; J A Caminero Journal: Int J Tuberc Lung Dis Date: 2016-08 Impact factor: 2.373
Authors: F Qazi; U Khan; S Khowaja; M Javaid; A Ahmed; N Salahuddin; H Hussain; M C Becerra; J E Golub; A J Khan Journal: Int J Tuberc Lung Dis Date: 2011-11 Impact factor: 2.373
Authors: Kelly E Dooley; Carole D Mitnick; Mary Ann DeGroote; Ekwaro Obuku; Vera Belitsky; Carol D Hamilton; Mamodikoe Makhene; Sarita Shah; James C M Brust; Nadza Durakovic; Eric Nuermberger Journal: Clin Infect Dis Date: 2012-05-21 Impact factor: 9.079
Authors: L Lalande; L Bourguignon; S Bihari; P Maire; M Neely; R Jelliffe; S Goutelle Journal: Antimicrob Agents Chemother Date: 2015-06-15 Impact factor: 5.191