Published ahead of print on February 10, 2006, doi:10.1164/rccm.200512-1953OC Am. J. Respir. Crit. Care Med., Volume 173, Number 8, April 2006, 922-926 A more recent version of this article appeared on April 15, 2006
Submitted on December 22, 2005 A Trial of Weekly Rifapentine or Daily Rifampin, with Isoniazid, for Latent Tuberculosis in ContactsMauro Schechter1,1 Infectious Diseases Service, Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, Brazil; Projeto Praca Onze, Hospital Escola Sao Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 2 Johns Hopkins University, Center for Tuberculosis Research, Baltimore, MD, USA; Department of International Health, John Hopkins University, Baltimore, MD, USA, 3 Department of International Health, John Hopkins University, Baltimore, MD, USA, 4 Johns Hopkins University, Center for Tuberculosis Research, Baltimore, MD, USA; Department of Medicine, John Hopkins University, Baltimore, MD, USA; Department of Epidemiology, John Hopkins University, Baltimore, MD, USA * To whom correspondence should be addressed. E-mail: rchaiss{at}jhmi.edu.
Rationale: Treatment of latent tuberculosis 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 tuberculosis in household contacts of pulmonary tuberculosis patients in Brazil. Methods: Contacts of tuberculosis patients were randomized to rifapentine 900 mg/isoniazid 900 mg once weekly for 12 weeks or rifampin 450-600 mg/pyrazinamide 750-1500 mg daily for 8 weeks and followed for at least two years. Measurements: Tuberculosis rates, adverse events and adherence to therapy. Main Results: 399 household contacts were enrolled, 206 in the rifapentine/isoniazid arm and 193 in the rifampin/pyrazinamide arm. The median age was 34 years, 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 prior to completion because of unanticipated hepatotoxicity in the rifampin/pyrazinamide arm. 20/193 participants (10%) receiving rifampin/pyrazinamide experienced Grade 3 or 4 hepatotoxicity, compared to 2/206 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 tuberculosis developed, three in the rifapentine/isoniazid group and one in the rifampin/pyrazinamide group (1.46% vs. 0.52%, difference 0.94%, 95% CI -1.6% - 3.7%). Conclusions: Rifapentine/isoniazid was better tolerated than rifampin/pyrazinamide and was associated with good protection against tuberculosis. Rifapentine/isoniazid weekly for 12 weeks is a likely promising therapy for latent TB infection. Key words: Tuberculosis, chemoprophylaxis, rifapentine, clinical trial
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