Assessment of a combined preparation of isoniazid, rifampicin and pyrazinamide (Rifater) in the initial phase of chemotherapy in three 6-month regimens for smear-positive pulmonary tuberculosis: a five-year follow-up report.

Setting: Singapore Tuberculosis Service.
Objective: To assess the acceptability, efficacy and relapse rate of a combined formulation of three drugs--isoniazid, rifampicin and pyrazinamide (Rifater)--given in the initial phase of chemotherapy in three 6-month regimens (2SHRZ/4H3R3, 1SHRZ/5H3R3 and 2HRZ/4H3R3) under direct observation for all patients.
Design: A randomised, controlled, unblinded study comparing a group of patients treated with Rifater and another given the three component drugs as separate formulations.
Results: The 310 patients admitted to the study were divided into two groups of 155 patients. The frequency of side effects was similar in both groups. Of 271 patients with drug-sensitive strains who had completed treatment without interruption, sputum cultures converted in all patients. At the end of 5 years, there were 15 relapses: three (2.2%) in the separate drugs group and 12 (9.3%) in the Rifater group. Exclusion of two cases in the Rifater group, one with silicotuberculosis and another with no bacteriological confirmation of diagnosis, gave a relapse rate of 7.9% (P = 0.03 for the comparison of relapse rates in the two groups).
Conclusion: A combined formulation of three drugs given daily in the initial phase of 6-month short-course therapy, followed by intermittent treatment with isoniazid and rifampicin given three times a week under direct observation for all patients, appears to be less effective than treatment with the component drugs given as separate formulations.