PLoS ONE (Jan 2013)

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

  • Mohideen S Jawahar,
  • Vaithilingam V Banurekha,
  • Chinnampedu N Paramasivan,
  • Fathima Rahman,
  • Rajeswari Ramachandran,
  • Perumal Venkatesan,
  • Rani Balasubramanian,
  • Nagamiah Selvakumar,
  • Chinnaiyan Ponnuraja,
  • Allaudeen S Iliayas,
  • Navaneethapandian P Gangadevi,
  • Balambal Raman,
  • Dhanaraj Baskaran,
  • Santhanakrishnan R Kumar,
  • Marimuthu M Kumar,
  • Victor Mohan,
  • Sudha Ganapathy,
  • Vanaja Kumar,
  • Geetha Shanmugam,
  • Niruparani Charles,
  • Murugesan R Sakthivel,
  • Kannivelu Jagannath,
  • Chockalingam Chandrasekar,
  • Ramavaram T Parthasarathy,
  • Paranji R Narayanan

DOI
https://doi.org/10.1371/journal.pone.0067030
Journal volume & issue
Vol. 8, no. 7
p. e67030

Abstract

Read online

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.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.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.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.Clinical Trials Registry of India CTRI/2012/10/003060.