"UNITED-STATES-PUBLIC-HEALTH-SERVICE COOPERATIVE TRIAL OF 3 RIFAMPIN-ISONIAZID REGIMENS IN TREATMENT OF PULMONARY TUBERCULOSIS

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Abstract
A total of 822 patients with newly diagnosed pulmonary tuberculosis were assigned randomly to one of 3 daily rifampin-isoniazid (RIF-INH) regimens: 450, 600 or 750 mg of RIF in combination with 300 mg of INH. After an initial 20 wk of therapy with RIF-INH, patients received 300 mg of INH and 15 mg of ethambutol (EMB)/kg of body weight for 12 or 18 mo. after their sputum cultures became negative. The rate of bacteriologic conversion of sputum among the 3 RIF-INH regimens was compared for 552 patients who completed the 20 wk of RIF-INH therapy. Approximately 60% of these patients also completed their assigned INH-EMB therapy and were examined for relapse for at least 1 yr after therapy was stopped. There was no significant difference in the rate of sputum conversion or rate of relapse between the group of patients who received 600 mg of RIF and those who received 750 mg of RIF. The 450-mg RIF regimen was significantly less effective than the other 2 regimens, as manifested by a lower rate of sputum conversion and a higher rate of treatment failures. Further analysis showed that RIF dosages of less than 9 mg/kg of body weight per day may be inadequate for treatment of pulmonary tuberculosis. The acceptability of these regimens was high, and the incidence of adverse reactions requiring discontinuation of RIF-INH therapy was quite low (3.3%). A large proportion of patients (44%) developed increased concentration of transaminase during therapy with RIF-INH. These abnormalities were usually transient and, in most cases, of no clinical significance. In the relapse analysis, 12 mo. of chemotherapy after sputum conversion were shown to be as effective as 18 mo. of therapy after conversion of these RIF-containing regimens.