title: A four-month gatifloxacin-containing regimen for treating tuberculosis.
abstract: BACKGROUND
  Shortening the course of treatment for tuberculosis would be a major improvement for case management and disease control. This phase 3 trial assessed the efficacy and safety of a 4-month gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis.
  
  
  METHODS
  We conducted a noninferiority, randomized, open-label, controlled trial involving patients 18 to 65 years of age with smear-positive, rifampin-sensitive, newly diagnosed pulmonary tuberculosis in five sub-Saharan African countries. A standard 6-month regimen that included ethambutol during the 2-month intensive phase was compared with a 4-month regimen in which gatifloxacin (400 mg per day) was substituted for ethambutol during the intensive phase and was continued, along with rifampin and isoniazid, during the continuation phase. The primary efficacy end point was an unfavorable outcome (treatment failure, recurrence, or death or study dropout during treatment) measured 24 months after the end of treatment, with a noninferiority margin of 6 percentage points, adjusted for country.
  
  
  RESULTS
  A total of 1836 patients were assigned to the 4-month regimen (experimental group) or the standard regimen (control group). Baseline characteristics were well balanced between the groups. At 24 months after the end of treatment, the adjusted difference in the risk of an unfavorable outcome (experimental group [21.0%] minus control group [17.2%]) in the modified intention-to-treat population (1356 patients) was 3.5 percentage points (95% confidence interval, -0.7 to 7.7). There was heterogeneity across countries (P=0.02 for interaction, with differences in the rate of an unfavorable outcome ranging from -5.4 percentage points in Guinea to 12.3 percentage points in Senegal) and in baseline cavitary status (P=0.04 for interaction) and body-mass index (P=0.10 for interaction). The standard regimen, as compared with the 4-month regimen, was associated with a higher dropout rate during treatment (5.0% vs. 2.7%) and more treatment failures (2.4% vs. 1.7%) but fewer recurrences (7.1% vs. 14.6%). There was no evidence of increased risks of prolongation of the QT interval or dysglycemia with the 4-month regimen.
  
  
  CONCLUSIONS
  Noninferiority of the 4-month regimen to the standard regimen with respect to the primary efficacy end point was not shown. (Funded by the Special Program for Research and Training in Tropical Diseases and others; ClinicalTrials.gov number, NCT00216385.).
authors.affiliation: From the London School of Hygiene and Tropical Medicine, London (C.S.M., K.F., C.S.), and Tropical Projects, Hitchin (J.H.) - both in the United Kingdom; Service de Pneumo-phtisiologie, Hôpital Ignace Deen, Conakry, Guinea (O.B.S., B.B.); Centre National Hospitalier de Pneumo-phtisiologie, Cotonou, Benin (M.G., F.K.); Programme National de Lutte contre la Tuberculose, Dakar, Senegal (M.B.L., A.N.); Medical Research Council, Durban, South Africa (T.M., R.R.); Kenya Medical Research Institute, Nairobi (J.O., E.A.); Institute of Tropical Medicine, Antwerp, Belgium (B.C.J.); Hôpitaux Universitaires Paris Ile-de-France Ouest, Assistance Publique-Hôpitaux de Paris, Paris (C.P.), and Institut de Recherche pour le Développement, Marseille (O.L., C.L.) - both in France; and Special Program for Research and Training in Tropical Diseases, World Health Organization, Geneva (P.L.O.).
authors.forename: Corinne S
authors.initials: CS
authors.lastname: Merle
authors.forename: Katherine
authors.initials: K
authors.lastname: Fielding
authors.forename: Omou Bah
authors.initials: OB
authors.lastname: Sow
authors.forename: Martin
authors.initials: M
authors.lastname: Gninafon
authors.forename: Mame B
authors.initials: MB
authors.lastname: Lo
authors.forename: Thuli
authors.initials: T
authors.lastname: Mthiyane
authors.forename: Joseph
authors.initials: J
authors.lastname: Odhiambo
authors.forename: Evans
authors.initials: E
authors.lastname: Amukoye
authors.forename: Boubacar
authors.initials: B
authors.lastname: Bah
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Kassa
authors.forename: Alimatou
authors.initials: A
authors.lastname: N'Diaye
authors.forename: Roxana
authors.initials: R
authors.lastname: Rustomjee
authors.forename: Bouke C
authors.initials: BC
authors.lastname: de Jong
authors.forename: John
authors.initials: J
authors.lastname: Horton
authors.forename: Christian
authors.initials: C
authors.lastname: Perronne
authors.forename: Charalambos
authors.initials: C
authors.lastname: Sismanidis
authors.forename: Olivier
authors.initials: O
authors.lastname: Lapujade
authors.forename: Piero L
authors.initials: PL
authors.lastname: Olliaro
authors.forename: Christian
authors.initials: C
authors.lastname: Lienhardt
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000627:therapeutic use; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects / Q000627:therapeutic use*; D000077734:Gatifloxacin; D006801:Humans; D057194:Intention to Treat Analysis; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D001786:Blood Glucose; D024841:Fluoroquinolones; D011718:Pyrazinamide; D004977:Ethambutol; D000077734:Gatifloxacin; D007538:Isoniazid; D012293:Rifampin