Results at 30 months of a randomised trial of two 8-month regimens for the treatment of tuberculosis

Int J Tuberc Lung Dis. 2011 Jun;15(6):741-5. doi: 10.5588/ijtld.10.0392.


Setting: 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.

Design: 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).

Conclusion: 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 The WHO has withdrawn its recommendation of these regimens.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibiotics, Antitubercular / therapeutic use
  • Antitubercular Agents / therapeutic use*
  • Drug Combinations
  • Drug Therapy, Combination
  • Ethambutol / therapeutic use*
  • Female
  • Humans
  • Intention to Treat Analysis
  • Isoniazid / therapeutic use*
  • Male
  • Middle Aged
  • Pyrazinamide / therapeutic use*
  • Rifampin / therapeutic use*
  • Sputum / microbiology
  • Treatment Failure
  • Tuberculosis, Pulmonary / drug therapy*
  • World Health Organization
  • Young Adult


  • Antibiotics, Antitubercular
  • Antitubercular Agents
  • Drug Combinations
  • Pyrazinamide
  • Ethambutol
  • Isoniazid
  • Rifampin