• 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, and Paranji R Narayanan.
• National Institute for Research in Tuberculosis formerly Tuberculosis Research Centre, Chennai, India.
• Plos One. 2013 Jan 1;8(7):e67030.

BackgroundShortening 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.MethodsNewly 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.ResultsOf 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.Conclusions4-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 RegistrationClinical Trials Registry of India CTRI/2012/10/003060.

32 keywords...

hide…