title: A randomised controlled trial of high-dose isoniazid adjuvant therapy for multidrug-resistant tuberculosis.
abstract: METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Tuberculosis & Respiratory Diseases, Ganesh Shankar Vidyarthi Memorial Medical College, Kanpur, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Katiyar
authors.forename: S
authors.initials: S
authors.lastname: Bihari
authors.forename: S
authors.initials: S
authors.lastname: Prakash
authors.forename: M
authors.initials: M
authors.lastname: Mamtani
authors.forename: H
authors.initials: H
authors.lastname: Kulkarni
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid