Three months of rifapentine and isoniazid for latent tuberculosis infection

Timothy R. Sterling, M. Elsa Villarino, Andrey S. Borisov, Nong Shang, Fred Gordin, Erin Bliven-Sizemore, Judith Hackman, Carol Dukes Hamilton, Dick Menzies, Amy Kerrigan, Stephen Weis, Marc Weiner, Diane Wing, Marcus B. Conde, Lorna Bozeman, C. Robert Horsburgh, Richard E. Chaisson

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Abstract

BACKGROUND: Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion. METHODS: We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain and followed for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75%. RESULTS: In the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1% in the combination- therapy group and 69.0% in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination- therapy group and 3.7% in the isoniazid-only group (P = 0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001). CONCLUSIONS: The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.)

Original languageEnglish
Pages (from-to)2155-2166
Number of pages12
JournalNew England Journal of Medicine
Volume365
Issue number23
DOIs
StatePublished - 8 Dec 2011

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rifapentine
Latent Tuberculosis
Isoniazid
Group Psychotherapy
Tuberculosis
Mycobacterium Infections
Intention to Treat Analysis

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Sterling, T. R., Villarino, M. E., Borisov, A. S., Shang, N., Gordin, F., Bliven-Sizemore, E., ... Chaisson, R. E. (2011). Three months of rifapentine and isoniazid for latent tuberculosis infection. New England Journal of Medicine, 365(23), 2155-2166. https://doi.org/10.1056/NEJMoa1104875
Sterling, Timothy R. ; Villarino, M. Elsa ; Borisov, Andrey S. ; Shang, Nong ; Gordin, Fred ; Bliven-Sizemore, Erin ; Hackman, Judith ; Hamilton, Carol Dukes ; Menzies, Dick ; Kerrigan, Amy ; Weis, Stephen ; Weiner, Marc ; Wing, Diane ; Conde, Marcus B. ; Bozeman, Lorna ; Horsburgh, C. Robert ; Chaisson, Richard E. / Three months of rifapentine and isoniazid for latent tuberculosis infection. In: New England Journal of Medicine. 2011 ; Vol. 365, No. 23. pp. 2155-2166.
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title = "Three months of rifapentine and isoniazid for latent tuberculosis infection",
abstract = "BACKGROUND: Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion. METHODS: We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain and followed for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75{\%}. RESULTS: In the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19{\%}) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43{\%}), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1{\%} in the combination- therapy group and 69.0{\%} in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9{\%} in the combination- therapy group and 3.7{\%} in the isoniazid-only group (P = 0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4{\%} and 2.7{\%}, respectively (P<0.001). CONCLUSIONS: The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.)",
author = "Sterling, {Timothy R.} and Villarino, {M. Elsa} and Borisov, {Andrey S.} and Nong Shang and Fred Gordin and Erin Bliven-Sizemore and Judith Hackman and Hamilton, {Carol Dukes} and Dick Menzies and Amy Kerrigan and Stephen Weis and Marc Weiner and Diane Wing and Conde, {Marcus B.} and Lorna Bozeman and Horsburgh, {C. Robert} and Chaisson, {Richard E.}",
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Sterling, TR, Villarino, ME, Borisov, AS, Shang, N, Gordin, F, Bliven-Sizemore, E, Hackman, J, Hamilton, CD, Menzies, D, Kerrigan, A, Weis, S, Weiner, M, Wing, D, Conde, MB, Bozeman, L, Horsburgh, CR & Chaisson, RE 2011, 'Three months of rifapentine and isoniazid for latent tuberculosis infection', New England Journal of Medicine, vol. 365, no. 23, pp. 2155-2166. https://doi.org/10.1056/NEJMoa1104875

Three months of rifapentine and isoniazid for latent tuberculosis infection. / Sterling, Timothy R.; Villarino, M. Elsa; Borisov, Andrey S.; Shang, Nong; Gordin, Fred; Bliven-Sizemore, Erin; Hackman, Judith; Hamilton, Carol Dukes; Menzies, Dick; Kerrigan, Amy; Weis, Stephen; Weiner, Marc; Wing, Diane; Conde, Marcus B.; Bozeman, Lorna; Horsburgh, C. Robert; Chaisson, Richard E.

In: New England Journal of Medicine, Vol. 365, No. 23, 08.12.2011, p. 2155-2166.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Three months of rifapentine and isoniazid for latent tuberculosis infection

AU - Sterling, Timothy R.

AU - Villarino, M. Elsa

AU - Borisov, Andrey S.

AU - Shang, Nong

AU - Gordin, Fred

AU - Bliven-Sizemore, Erin

AU - Hackman, Judith

AU - Hamilton, Carol Dukes

AU - Menzies, Dick

AU - Kerrigan, Amy

AU - Weis, Stephen

AU - Weiner, Marc

AU - Wing, Diane

AU - Conde, Marcus B.

AU - Bozeman, Lorna

AU - Horsburgh, C. Robert

AU - Chaisson, Richard E.

PY - 2011/12/8

Y1 - 2011/12/8

N2 - BACKGROUND: Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion. METHODS: We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain and followed for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75%. RESULTS: In the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1% in the combination- therapy group and 69.0% in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination- therapy group and 3.7% in the isoniazid-only group (P = 0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001). CONCLUSIONS: The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.)

AB - BACKGROUND: Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion. METHODS: We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain and followed for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75%. RESULTS: In the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1% in the combination- therapy group and 69.0% in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination- therapy group and 3.7% in the isoniazid-only group (P = 0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001). CONCLUSIONS: The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.)

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DO - 10.1056/NEJMoa1104875

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Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. New England Journal of Medicine. 2011 Dec 8;365(23):2155-2166. https://doi.org/10.1056/NEJMoa1104875