Setting: Patients with newly-diagnosed drug-sensitive, radiographically active and bacteriologically confirmed pulmonary tuberculosis recruited at 6 centres in Argentina, Brazil and Thailand.
Objective: To assess the efficacy, tolerability and toxicity of two regimens containing different daily dosages of rifabutin in comparison with rifampicin.
Design: Multicentred, randomised, comparative study. In each group, study medications were administered daily for 6 months combined with isoniazid (6 months), and with pyrazinamide and ethambutol (both stopped after 2 months). Treatment success patients were followed-up for up to 2 years.
Results: A total of 520 patients were enrolled and randomly assigned to receive either rifampicin (n = 175), or rifabutin 150 mg (n = 174) or rifabutin 300 mg (n = 171). Considering all patients with positive baseline culture, the success rates at the last valid observation for each patient were 89%, 94% and 92% in the rifampicin, rifabutin 150 mg, and rifabutin 300 mg groups, respectively. The median time to culture conversion was comparable in the 3 groups and was 34 days for rifampicin and 37 days for each of the rifabutin groups. During the drug-free follow-up period, one relapse occurred in the rifampicin group, and two in each of the rifabutin groups. The 3 treatment schedules appeared well tolerated. No patients had to discontinue therapy because of an adverse event in the rifabutin 150 mg group, compared to one in the rifampicin and 5 in the rifabutin 300 mg group.
Conclusion: All 3 regimens proved effective and well tolerated. Rifabutin at 150 mg/d showed the best risk-to-benefit ratio, in that this group had the highest proportion of patients completing treatment, the highest bacteriological conversion rates and the lowest incidence of adverse events.