title: Results at 30 months of a randomised trial of two 8-month regimens for the treatment of tuberculosis.
abstract: METHODS
  An 8-month isoniazid (INH, H) and ethambutol (EMB, E) based regimen recommended by the World Health Organization (WHO) had never been evaluated in a randomised controlled multicentre trial.
  
  
  OBJECTIVE
  To compare, in a non-inferiority study design, two 8-month INH+EMB-based regimens with a standard INH and rifampicin (RMP, R) based regimen.
  
  
  METHODS
  A total of 1355 patients with newly diagnosed smear-positive pulmonary tuberculosis were randomly allocated to receive 1) daily EMB, INH, RMP and pyrazinamide (PZA, Z) for 2 months, followed by EMB+INH for 6 months (2EHRZ/6HE); 2) the same drugs in the intensive phase but given three times weekly, followed by the same continuation phase of daily EMB+INH (2(EHRZ)(3)/6HE); or 3) a control regimen with the same intensive phase as in regimen 1, followed by 4 months of daily RMP+INH (2EHRZ/4HR). All patients were to be seen and sputum examinations for microscopy and culture carried out at regular intervals up to 30 months after randomisation.
  
  
  RESULTS
  At 30 months, failure/relapse rates were 11.7% of 281 2EHRZ/6HE, 15.3% of 301 2(EHRZ)(3)/6HE and 6.0% of 282 2EHRZ/4HR patients (χ(2), 2 degrees of freedom = 12.8, P = 0.002).
  
  
  CONCLUSIONS
  These results confirm earlier findings demonstrating the inferiority of the INH+EMB-based regimens to the standard 6-month regimen. The WHO has withdrawn its recommendation of these regimens.
authors.affiliation: Medical Research Council Clinical Trials Unit, London, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Nunn
authors.forename: A
authors.initials: A
authors.lastname: Jindani
authors.forename: D A
authors.initials: DA
authors.lastname: Enarson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D007538:Isoniazid / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011718:Pyrazinamide / Q000627:therapeutic use*; D012293:Rifampin / Q000627:therapeutic use*; D013183:Sputum / Q000382:microbiology; D017211:Treatment Failure; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*; D014944:World Health Organization; D055815:Young Adult
chemical_list: D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D004338:Drug Combinations; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin