Randomized clinical trial of thrice-weekly 4-month moxifloxacin or gatifloxacin containing regimens in the treatment of new sputum positive pulmonary tuberculosis patients

PLoS One. 2013 Jul 3;8(7):e67030. doi: 10.1371/journal.pone.0067030. Print 2013.

Abstract

Background: Shortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India.

Methods: Newly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C). All regimens were administered thrice-weekly. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens.

Results: Of 416 patients in intent-to-treat analysis, 6 (5%) of 124, 2 (2%) of 110 and 2 (2%) of 137 patients with drug-susceptible TB in the G, M and C arms respectively had unfavorable response at the end of treatment; during the next 24 months, 17 (15%) of 115, 11 (11%) of 104 and 8 (6%) of 132 patients respectively, had TB recurrence. Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment; and TB recurrence occurred in 2 of 7 and 2 of 23 patients, respectively. The differences in TB recurrence rates between the G and C arms was statistically significant (p = 0.02). Gastro-intestinal symptoms occurred in 23%, 22% and 9% of patients in the G, M and C arms respectively, but most reactions were mild and manageable with symptomatic measures; 1% required regimen modification.

Conclusions: 4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid, rifampicin and pyrazinamide, were inferior to standard 6-month treatment, in patients with newly diagnosed sputum positive pulmonary TB.

Trial registration: Clinical Trials Registry of India CTRI/2012/10/003060.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / adverse effects
  • Antitubercular Agents / therapeutic use*
  • Aza Compounds / administration & dosage
  • Aza Compounds / therapeutic use*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fluoroquinolones / administration & dosage
  • Fluoroquinolones / adverse effects
  • Fluoroquinolones / therapeutic use*
  • Gatifloxacin
  • Humans
  • Male
  • Middle Aged
  • Moxifloxacin
  • Quinolines / administration & dosage
  • Quinolines / therapeutic use*
  • Recurrence
  • Sputum / microbiology
  • Treatment Outcome
  • Tuberculosis, Pulmonary / diagnosis
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / mortality
  • Young Adult

Substances

  • Antitubercular Agents
  • Aza Compounds
  • Fluoroquinolones
  • Quinolines
  • Gatifloxacin
  • Moxifloxacin

Grant support

The study was carried out utilising institutional funds of the Tuberculosis Research Centre of the Indian Council of Medical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.