Controlled clinical trial of 4 short-course regimens of chemotherapy (three 6-month and one 8-month) for pulmonary tuberculosis: final report. East and Central African/British Medical Research Council Fifth Collaborative Study

Abstract

The bacteriological relapse rates up to 30 months after the start of chemotherapy have been compared for 4 daily short-course regimens for pulmonary tuberculosis. All 4 had the same initial 2-month intensive phase of streptomycin, isoniazid, rifampicin and pyrazinamide (SHRZ) followed by isoniazid plus rifampicin for 4 months (4HR), or isoniazid plus pyrazinamide for 4 months (4HZ), or isoniazid alone for 4 months (4H), or isoniazid alone for 6 months (6H). In patients with fully sensitive strains pretreatment, the 6-month regimen with rifampicin throughout (4HR) was highly effective, only 2% of 166 patients relapsing bacteriologically in 24 months of follow-up after stopping chemotherapy. This regimen was significantly better than the 4H regimen which had a relapse rate of 10% in 156 patients (P less than 0.02) and the 4HZ regimen which had a relapse rate of 8% in 164 patients (P = 0.05). The 6H regimen was also highly effective, only 3% of the 123 patients relapsing, compared with 10% of the 156 on the 4H regimen (P = 0.06). The relapse rate of the regimen with pyrazinamide throughout (4HZ), was not significantly different from that of either of the regimens with isoniazid alone in the continuation phase. All except 3 (1 4HR, 1 4HZ, 1 4H) of the 36 relapses were with fully drug-sensitive strains. In patients with strains resistant to isoniazid alone pretreatment none of the 23 on the 4HR or 4HZ regimens had an unfavourable bacteriological status at the end of chemotherapy compared with 8 of the 17 patients (P less than 0.005) on 4H or 6H regimens. Of the patients assessed, 3 of 20 receiving rifampicin or pyrazinamide throughout relapsed compared with 2 of 8 who did not.