Published ahead of print on February 10, 2006, doi:10.1164/rccm.200512-1953OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200512-1953OC
Weekly Rifapentine/Isoniazid or Daily Rifampin/Pyrazinamide for Latent Tuberculosis in Household ContactsInfectious Diseases Service, Hospital Universitário Clementino Fraga Filho; Projeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Center for Tuberculosis Research and Departments of Medicine, Epidemiology, and International Health, Johns Hopkins University, Baltimore, Maryland Correspondence and requests for reprints should be addressed to Richard E. Chaisson, M.D., 1503 East Jefferson Street, Baltimore, MD 21231. E-mail: rchaiss{at}jhmi.edu Rationale: Treatment of latent tuberculosis (TB) infection with weekly rifapentine and isoniazid is a potentially effective alternative to current therapies. Objectives: To compare the efficacy of weekly rifapentine/isoniazid to daily rifampin/pyrazinamide in preventing TB in household contacts of patients with pulmonary TB in Brazil. Methods: Contacts of patients with TB were randomized to rifapentine 900 mg/isoniazid 900 mg once weekly for 12 wk or rifampin 450–600 mg/pyrazinamide 750–1,500 mg daily for 8 wk and followed for at least 2 yr. Measurements: TB rates, adverse events, and adherence to therapy. Main Results: A total of 399 household contacts were enrolled, 206 in the rifapentine/isoniazid arm and 193 in the rifampin/pyrazinamide arm. The median age was 34 yr, median weight was 63 kg, 60% of participants were female, and only one patient was HIV infected. Rifapentine/isoniazid was well tolerated, but the trial was halted by the investigators before completion because of unanticipated hepatotoxicity in the rifampin/pyrazinamide arm. Twenty of 193 participants (10%) receiving rifampin/pyrazinamide experienced grade 3 or 4 hepatotoxicity, compared with 2 of 206 participants (1%) on rifapentine/isoniazid (p < 0.001). There were no hospitalizations or deaths due to hepatotoxicity, and all participants' liver enzyme levels returned to normal during follow-up. During follow-up, four cases of active TB developed, three in the rifapentine/isoniazid group and one in the rifampin/pyrazinamide group (1.46 vs. 0.52%; difference, 0.94%; 95% confidence interval, –1.6 to 3.7%). Conclusions: Rifapentine/isoniazid was better tolerated than rifampin/pyrazinamide and was associated with good protection against TB. Rifapentine/isoniazid weekly for 12 wk is likely a promising therapy for latent TB infection.
Key Words: controlled clinical trial • latent tuberculosis • pyrazinamide • rifampin • rifapentine This article has been cited by other articles:
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