USPHS Tuberculosis Short-Course Chemotherapy Trial 21: effectiveness, toxicity, and acceptability. The report of final results.

STUDY OBJECTIVE

To determine the effectiveness, toxicity, and acceptability of a 6-month antituberculous regimen compared with a 9-month regimen.

DESIGN

A nonblinded, unbalanced, randomized, multicenter clinical trial.

SETTING

Twenty-two tuberculosis clinics in public health departments and hospitals in the United States.

PATIENTS

Patients were eligible if Mycobacterium tuberculosis, isolated from sputum cultures, was susceptible to study drugs. Of 1451 patients enrolled, 75% (617 of 823) assigned to the 6-month regimen and 71% (445 of 628) assigned to the 9-month regimen were eligible.

INTERVENTIONS

Patients took self-administered isoniazid and rifampin daily for 24 weeks (6-month regimen) or 36 weeks (9-month regimen). In addition, patients assigned to the 6-month regimen took self-administered pyrazinamide daily during the first 8 weeks.

RESULTS

Patients on the 6-month regimen converted more rapidly than patients on the 9-month regimen (94.6% compared with 89.9% after 16 weeks of therapy, with a difference of 4.7% [95% CI, 0.7% to 8.7%]); had similar rates of adverse drug reactions (7.7% compared with 6.4%, with a difference of 1.3% [95% CI, 0.0% to 4.6%]); had lower noncompliance rates (16.8% compared with 29.2%, with a difference of 12.4% [95% CI, 6.8% to 18.0%]); and had similar relapse rates 96 weeks after completing therapy (3.5% compared with 2.8%, with a difference of 0.7% [95% CI, 0.0% to 3.9%]). A significantly greater proportion of patients assigned to the 6-month regimen successfully completed therapy (61.4% compared with 50.6%; chi 2 = 11.976).

CONCLUSIONS

Our results suggest that this 6-month regimen is similar in effectiveness, toxicity, and acceptability to the 9-month regimen for treating pulmonary tuberculosis.