title: Randomized clinical trial of thrice-weekly 4-month moxifloxacin or gatifloxacin containing regimens in the treatment of new sputum positive pulmonary tuberculosis patients.
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.
  
  
  BACKGROUND
  Clinical Trials Registry of India CTRI/2012/10/003060.
authors.affiliation: National Institute for Research in Tuberculosis formerly Tuberculosis Research Centre, Chennai, India.
authors.forename: Mohideen S
authors.initials: MS
authors.lastname: Jawahar
authors.forename: Vaithilingam V
authors.initials: VV
authors.lastname: Banurekha
authors.forename: Chinnampedu N
authors.initials: CN
authors.lastname: Paramasivan
authors.forename: Fathima
authors.initials: F
authors.lastname: Rahman
authors.forename: Rajeswari
authors.initials: R
authors.lastname: Ramachandran
authors.forename: Perumal
authors.initials: P
authors.lastname: Venkatesan
authors.forename: Rani
authors.initials: R
authors.lastname: Balasubramanian
authors.forename: Nagamiah
authors.initials: N
authors.lastname: Selvakumar
authors.forename: Chinnaiyan
authors.initials: C
authors.lastname: Ponnuraja
authors.forename: Allaudeen S
authors.initials: AS
authors.lastname: Iliayas
authors.forename: Navaneethapandian P
authors.initials: NP
authors.lastname: Gangadevi
authors.forename: Balambal
authors.initials: B
authors.lastname: Raman
authors.forename: Dhanaraj
authors.initials: D
authors.lastname: Baskaran
authors.forename: Santhanakrishnan R
authors.initials: SR
authors.lastname: Kumar
authors.forename: Marimuthu M
authors.initials: MM
authors.lastname: Kumar
authors.forename: Victor
authors.initials: V
authors.lastname: Mohan
authors.forename: Sudha
authors.initials: S
authors.lastname: Ganapathy
authors.forename: Vanaja
authors.initials: V
authors.lastname: Kumar
authors.forename: Geetha
authors.initials: G
authors.lastname: Shanmugam
authors.forename: Niruparani
authors.initials: N
authors.lastname: Charles
authors.forename: Murugesan R
authors.initials: MR
authors.lastname: Sakthivel
authors.forename: Kannivelu
authors.initials: K
authors.lastname: Jagannath
authors.forename: Chockalingam
authors.initials: C
authors.lastname: Chandrasekar
authors.forename: Ramavaram T
authors.initials: RT
authors.lastname: Parthasarathy
authors.forename: Paranji R
authors.initials: PR
authors.lastname: Narayanan
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001372:Aza Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077734:Gatifloxacin; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D012008:Recurrence; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077734:Gatifloxacin; D000077266:Moxifloxacin