TY - JOUR
T1 - Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients
T2 - A randomised clinical trial
AU - Benator, Debra
AU - Bhattacharya, Mondira
AU - Bozeman, Lorna
AU - Burman, William
AU - Catanzaro, Antonino
AU - Chaisson, Richard
AU - Gordin, Fred
AU - Horsburgh, C. Robert
AU - Horton, James
AU - Khan, Awal
AU - Lahart, Christopher
AU - Metchock, Beverly
AU - Pachucki, Constance
AU - Stanton, Llewellyn
AU - Vernon, Andrew
AU - Villarino, M. Elsa
AU - Yong, Cheng Wang
AU - Weiner, Marc
AU - Weis, Stephen
AU - Horsburgh, C. Robert
AU - Burman, William
N1 - Funding Information:
We thank the patients who contributed to this trial; the trial's data and safety monitoring board; Lawrence Geiter, who helped to create the clinical consortium that did this trial; Kenneth Castro for support and leadership within CDC; and local tuberculosis programme staff, who assisted in clinical management of participants. This study was funded by the Centers for Disease Control and Prevention, US Public Health Service. Rifapentine was kindly provided by Hoechst Marion Roussel, Kansas City, MO, USA, who also helped to defray the cost of three investigator meetings. The UCSD site acknowledges the services of the General Clinical Research Centre, supported by NIH grant M01-RR00827. This study was presented in part at the 2000 International Conference of the American Thoracic Society, Toronto, Canada.
PY - 2002/8/17
Y1 - 2002/8/17
N2 - Background: Rifapentine has a long half-life in serum, which suggests a possible treatment once a week for tuberculosis. We aimed to compare rifapentine and isoniazid once a week with rifampicin and isoniazid twice a week. Methods: We did a randomised, multicentre, open-label trial in the USA and Canada of HIV-negative people with drug-susceptible pulmonary tuberculosis who had completed 2 months of a 6-month treatment regimen. We randomly allocated patients directly observed treatment with either 600 mg rifapentine plus 900 mg isoniazid once a week or 600 mg rifampicin plus 900 mg isoniazid twice a week. Primary outcome was failure/relapse. Analysis was by intention to treat. Findings: 1004 patients were enrolled (502 per treatment group). 928 successfully completed treatment, and 803 completed the 2-year 4-month study. Crude rates of failure/relapse were 46/502 (9.2%) in those on rifapentine once a week, and 28/502 (5.6%) in those given rifampicin twice a week (relative risk 1.64, 95% CI 1.04-2.58, p=0.04). By proportional hazards regression, five characteristics were independently associated with increased risk of failure/relapse: sputum culture positive at 2 months (hazard ratio 2.8, 95% CI 1.7-4.6); cavitation on chest radiography (3.0, 1.6-5.9); being underweight (3.0, 1.8-4.9); bilateral pulmonary involvement (1.8, 1.0-3.1); and being a non-Hispanic white person (1.8, 1.1-3.0). Adjustment for imbalances in 2-month culture and cavitation diminished the association of treatment group with outcome (1.34; 0.83-2.18; p=0.23). Of participants without cavitation, rates of failure/relapse were 6/210 (2.9%) in the once a week group and 6/241 (2.5%) in the twice a week group (relative risk 1.15; 95% CI 0.38-3.50; p=0.81). Rates of adverse events and death were similar in the two treatment groups. Interpretation: Rifapentine once a week is safe and effective for treatment of pulmonary tuberculosis in HIV-negative people without cavitation on chest radiography. Clinical, radiographic, and microbiological data help to identify patients with tuberculosis who are at increased risk of failure or relapse when treated with either regimen.
AB - Background: Rifapentine has a long half-life in serum, which suggests a possible treatment once a week for tuberculosis. We aimed to compare rifapentine and isoniazid once a week with rifampicin and isoniazid twice a week. Methods: We did a randomised, multicentre, open-label trial in the USA and Canada of HIV-negative people with drug-susceptible pulmonary tuberculosis who had completed 2 months of a 6-month treatment regimen. We randomly allocated patients directly observed treatment with either 600 mg rifapentine plus 900 mg isoniazid once a week or 600 mg rifampicin plus 900 mg isoniazid twice a week. Primary outcome was failure/relapse. Analysis was by intention to treat. Findings: 1004 patients were enrolled (502 per treatment group). 928 successfully completed treatment, and 803 completed the 2-year 4-month study. Crude rates of failure/relapse were 46/502 (9.2%) in those on rifapentine once a week, and 28/502 (5.6%) in those given rifampicin twice a week (relative risk 1.64, 95% CI 1.04-2.58, p=0.04). By proportional hazards regression, five characteristics were independently associated with increased risk of failure/relapse: sputum culture positive at 2 months (hazard ratio 2.8, 95% CI 1.7-4.6); cavitation on chest radiography (3.0, 1.6-5.9); being underweight (3.0, 1.8-4.9); bilateral pulmonary involvement (1.8, 1.0-3.1); and being a non-Hispanic white person (1.8, 1.1-3.0). Adjustment for imbalances in 2-month culture and cavitation diminished the association of treatment group with outcome (1.34; 0.83-2.18; p=0.23). Of participants without cavitation, rates of failure/relapse were 6/210 (2.9%) in the once a week group and 6/241 (2.5%) in the twice a week group (relative risk 1.15; 95% CI 0.38-3.50; p=0.81). Rates of adverse events and death were similar in the two treatment groups. Interpretation: Rifapentine once a week is safe and effective for treatment of pulmonary tuberculosis in HIV-negative people without cavitation on chest radiography. Clinical, radiographic, and microbiological data help to identify patients with tuberculosis who are at increased risk of failure or relapse when treated with either regimen.
UR - http://www.scopus.com/inward/record.url?scp=0037125569&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(02)09742-8
DO - 10.1016/S0140-6736(02)09742-8
M3 - Article
C2 - 12241657
AN - SCOPUS:0037125569
SN - 0140-6736
VL - 360
SP - 528
EP - 534
JO - The Lancet
JF - The Lancet
IS - 9332
ER -