Results of a randomized, controlled trial to assess the toxicity and patient adherence with two short-course regimens for the prevention of tuberculosis, a two-month regimen of rifampin and pyrazinamide or a four-month regimen of rifampin only, in comparison with a control regimen of six-months-isoniazid.

摘要

Preventive therapy with isoniazid for tuberculin skin test positive individuals has been an important part of tuberculosis control programs in North America. However, effectiveness is limited by poor adherence associated with long duration regimes and the risks of adverse reactions associated with isoniazid. Shorter course preventive therapy regimens containing rifampin offer the potential of increasing adherence and improving the effectiveness of the intervention. The objective of this trial was to evaluate the toxicity and patient adherence associated with two new regimens of preventive therapy for tuberculosis: (1) an eight-week regimen of daily rifampin and pyrazinamide and (2) a 16-week regimen of daily rifampin, compared with a control regimen of 24 weeks of isoniazid daily. The study was designed as a multi-center, randomized, controlled trial with no masking of the treatment or control regimens. Treatment allocations were stratified by treatment center. A total of 402 eligible patients were enrolled. Completion rates were 65% for the rifampin-pyrazinamide regimen, a 57% for the isoniazid regimen, and 42% rifampin regimen. For the rifampin-pyrazinamide regimen 5.8% stopped therapy due to an adverse reaction, compared with 0.8% for the isoniazid regimen and none for the rifampin-only regimen. Based on these results, rifampin-pyrazinamide regimens are unlikely to be practical for preventive therapy due to high rates of hepatotoxicity and relatively high rates of non-adherence. On-going efficacy studies may lead to a different conclusion if toxicity is lower and there is evidence of superior efficacy. A regimen of rifampin alone could prove attractive and short-course preventive therapy regimens with rifapentine spaced as widely as once a week should be considered for study.