Pneumology, Pneumologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences biologiques fondamentales et appliquees. Psychologie, Fundamental and applied biological sciences. Psychology, Biologie moleculaire et cellulaire, Molecular and cellular biology, Coagulation sanguine. Cellules sanguines, Blood coagulation. Blood cells, Thrombocyte, Platelet, Sciences medicales, Medical sciences, Pharmacologie. Traitements medicamenteux, Pharmacology. Drug treatments, Hormones. Glandes endocrines, Hormones. Endocrine system, Anesthesie. Reanimation. Transfusion. Therapie cellulaire et therapie genique, Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy, Réanimation. Soins intensifs, Intensive care medicine, Bactériose, Bacteriosis, Infection, Infección, Mycobactériose, Mycobacterial infection, Micobacteriosis, Antibactérien, Antibacterial agent, Antibacteriano, Antibiotique, Antibiotic, Antibiótico, Antituberculeux, Antituberculous agent, Antituberculoso, Contact, Contacto, Latent, Latente, Pyrazinamide, Pirazinamida, Rifampicine, Rifampicin, Rifampicina, Rifapentine, Rifapentina, Réanimation, Resuscitation, Reanimación, Soin intensif, Intensive care, Cuidado intensivo, Tuberculose, Tuberculosis, Inhibiteur synthèse protéique, controlled clinical trial, latent tuberculosis, pyrazinamide, rifampin, and rifapentine
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.