Assessment of a combined preparation of isoniazid, rifampicin and pyrazinamide (Rifater (R)) 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 comb ined formulation of three drugs-isoniazid, rifampicin and pyrazinamide (Rif ate(R))-given in the initial phase of chemotherapy in three 4-month regimen s (2SHRZ-4H(3)R(3), 1SHRZ/5H(3)R(3) and 2HRZ/4H(3)R(3)) under direct observ ation for all patients. DESIGN: A randomised, controlled, unblinded study comparing a group of pati ents treated with Rifater(R) and another given the three component drugs as separate formulations. RESULTS: The 310 patients admitted to the study were divided into two group s of 155 patients. The frequency of side effects was similar in both groups . Of 271 patients with drug-sensitive strains who had completed treatment w ithout interruption, sputum cultures converted in all patients. At the end of 5 years, there were 15 relapses: three (2.2%) in the separate drugs grou p and 12 (9.3%) in the Rifate(R) group. Exclusion of two cases in the Rifat er(R) group, one with silicotuberculosis and another with no bacteriologica l 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 initia l phase of 6-month shore-course therapy, followed by intermittent treatment with isoniazid and rifampicin given three times a week under direct observ ation for all patients, appears to be less effective than treatment with th e component drugs given as separate formulations.