Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients: A randomised clinical trial

Debra Benator, Mondira Bhattacharya, Lorna Bozeman, William Burman, Antonino Catanzaro, Richard Chaisson, Fred Gordin, C. Robert Horsburgh, James Horton, Awal Khan, Christopher Lahart, Beverly Metchock, Constance Pachucki, Llewellyn Stanton, Andrew Vernon, M. Elsa Villarino, Cheng Wang Yong, Marc Weiner, Stephen Weis, C. Robert HorsburghWilliam Burman

Research output: Contribution to journalArticle

334 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)528-534
Number of pages7
JournalLancet
Volume360
Issue number9332
DOIs
StatePublished - 17 Aug 2002

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rifapentine
Isoniazid
Rifampin
Pulmonary Tuberculosis
Randomized Controlled Trials
HIV
Pharmaceutical Preparations
Recurrence
Therapeutics
Radiography
Tuberculosis
Thorax
Intention to Treat Analysis
Thinness
Sputum

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Benator, Debra ; Bhattacharya, Mondira ; Bozeman, Lorna ; Burman, William ; Catanzaro, Antonino ; Chaisson, Richard ; Gordin, Fred ; Horsburgh, C. Robert ; Horton, James ; Khan, Awal ; Lahart, Christopher ; Metchock, Beverly ; Pachucki, Constance ; Stanton, Llewellyn ; Vernon, Andrew ; Villarino, M. Elsa ; Yong, Cheng Wang ; Weiner, Marc ; Weis, Stephen ; Horsburgh, C. Robert ; Burman, William. / Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients : A randomised clinical trial. In: Lancet. 2002 ; Vol. 360, No. 9332. pp. 528-534.
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abstract = "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.",
author = "Debra Benator and Mondira Bhattacharya and Lorna Bozeman and William Burman and Antonino Catanzaro and Richard Chaisson and Fred Gordin and Horsburgh, {C. Robert} and James Horton and Awal Khan and Christopher Lahart and Beverly Metchock and Constance Pachucki and Llewellyn Stanton and Andrew Vernon and Villarino, {M. Elsa} and Yong, {Cheng Wang} and Marc Weiner and Stephen Weis and Horsburgh, {C. Robert} and William Burman",
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Benator, D, Bhattacharya, M, Bozeman, L, Burman, W, Catanzaro, A, Chaisson, R, Gordin, F, Horsburgh, CR, Horton, J, Khan, A, Lahart, C, Metchock, B, Pachucki, C, Stanton, L, Vernon, A, Villarino, ME, Yong, CW, Weiner, M, Weis, S, Horsburgh, CR & Burman, W 2002, 'Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients: A randomised clinical trial', Lancet, vol. 360, no. 9332, pp. 528-534. https://doi.org/10.1016/S0140-6736(02)09742-8

Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients : A randomised clinical trial. / Benator, Debra; Bhattacharya, Mondira; Bozeman, Lorna; Burman, William; Catanzaro, Antonino; Chaisson, Richard; Gordin, Fred; Horsburgh, C. Robert; Horton, James; Khan, Awal; Lahart, Christopher; Metchock, Beverly; Pachucki, Constance; Stanton, Llewellyn; Vernon, Andrew; Villarino, M. Elsa; Yong, Cheng Wang; Weiner, Marc; Weis, Stephen; Horsburgh, C. Robert; Burman, William.

In: Lancet, Vol. 360, No. 9332, 17.08.2002, p. 528-534.

Research output: Contribution to journalArticle

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

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.

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DO - 10.1016/S0140-6736(02)09742-8

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AN - SCOPUS:0037125569

VL - 360

SP - 528

EP - 534

JO - The Lancet

JF - The Lancet

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