A controlled trial of a 4-weekly supplement of rifampicin, pyrazinamide and streptomycin in the continuation phase of a 7-month daily chemotherapy regimen for pulmonary tuberculosis. Tanzania/British Medical Research Council Collaborative Investigation.
OBJECTIVE
To evaluate a monthly 'pulse' of rifampicin plus pyrazinamide plus streptomycin in the continuation phase of a short-course antituberculosis regimen.


METHODS
Randomised controlled trial of two 7-month chemotherapy regimens.


METHODS
Inpatient chemotherapy and outpatient follow-up in Tanzania.


METHODS
Smear-positive pulmonary tuberculosis.


METHODS
All patients received streptomycin plus rifampicin plus isoniazid plus pyrazinamide daily for 6 weeks followed by isoniazid daily for 24 weeks; 50%, at random, received additional doses of rifampicin, pyrazinamide and streptomycin every 4 weeks in the continuation phase. Follow-up continued for 23 months after cessation of chemotherapy.


METHODS
Bacteriological failure rate at the end of chemotherapy and relapse rate after stopping.


RESULTS
Of the 266 patients with fully sensitive strains before treatment there was one failure in each series during chemotherapy; after stopping, 5% of the 114 who received the supplement relapsed bacteriologically compared with 10% of the 113 who did not (95% CI for the difference -0.02% to + 11.3%). The results in the 37 patients with strains resistant to isoniazid pretreatment were not as good, but similar for the two regimens.


CONCLUSIONS
This study was not large enough to demonstrate a significant reduction in the relapse rate from 10% to 5%. If such a reduction were confirmed in a larger study it would represent an important improvement in efficacy. further, in an outpatient setting, the additional monthly doses might improve attendance.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D044383:Black People; D001835:Body Weight; D004334:Drug Administration Schedule; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage* / Q000009:adverse effects; D007539:Isonicotinic Acids / Q000652:urine; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D011718:Pyrazinamide / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D012293:Rifampin / Q000008:administration & dosage* / Q000009:adverse effects; D013183:Sputum / Q000382:microbiology; D013307:Streptomycin / Q000008:administration & dosage* / Q000009:adverse effects; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology / Q000652:urine
D000995:Antitubercular Agents; D007539:Isonicotinic Acids; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin