Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis

Study 29 of the tuberculosis trials consortium

Susan E. Dorman, Stefan Goldberg, Jason E. Stout, Grace Muzanyi, John L. Johnson, Marc H Weiner, Lorna Bozeman, Charles M. Heilig, Pei Jean Feng, Ruth Moro, Masahiro Narita, Payam Nahid, Susan Ray, Edward Bates, Betial Haile, Eric L. Nuermberger, Andrew Vernon, Neil W. Schluger

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Background.Rifapentine administered 5 days per week has potent activity in mouse models of antituberculosis chemotherapy, but efficacy and safety data are limited in humans. We compared the antimicrobial activity and safety of rifapentine vs rifampin during the first 8 weeks of pulmonary tuberculosis treatment.Methods.In total, 531 adults with sputum smear-positive pulmonary tuberculosis were randomized to rifapentine 10 mg/kg/dose or rifampin 10 mg/kg/dose, administered 5 days per week for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. Coprimary outcomes were negative sputum culture on liquid and on solid media at completion of intensive phase.Results.Negative cultures on solid media occurred in 145 of 174 participants (83.3) in the rifampin group and 171 of 198 participants (86.4) in the rifapentine group (difference, 3.0; 95 confidence interval [CI]: - 4.3, 10.5); negative cultures in liquid media occurred in 110 of 169 (65.1) in the rifampin group and 133 of 196 (67.9) in the rifapentine group (difference, 2.8; 95 CI: -6.9, 12.4). Among 529 participants who received study therapy, 40 of 254 participants (15.7) in the rifampin group and 40 of 275 participants (14.5) in the rifapentine group prematurely discontinued treatment (P =. 79).Conclusions.The rifapentine regimen was safe but not significantly more active than a standard rifampin regimen, by the surrogate endpoint of culture status at completion of intensive phase. Assessment of higher exposures to rifapentine for tuberculosis treatment is warranted.

Original languageEnglish (US)
Pages (from-to)1030-1040
Number of pages11
JournalJournal of Infectious Diseases
Volume206
Issue number7
DOIs
StatePublished - Oct 1 2012

Fingerprint

rifapentine
Rifampin
Pulmonary Tuberculosis
Tuberculosis
Therapeutics
Sputum
Confidence Intervals
Pyrazinamide
Safety
Ethambutol
Isoniazid

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis : Study 29 of the tuberculosis trials consortium. / Dorman, Susan E.; Goldberg, Stefan; Stout, Jason E.; Muzanyi, Grace; Johnson, John L.; Weiner, Marc H; Bozeman, Lorna; Heilig, Charles M.; Feng, Pei Jean; Moro, Ruth; Narita, Masahiro; Nahid, Payam; Ray, Susan; Bates, Edward; Haile, Betial; Nuermberger, Eric L.; Vernon, Andrew; Schluger, Neil W.

In: Journal of Infectious Diseases, Vol. 206, No. 7, 01.10.2012, p. 1030-1040.

Research output: Contribution to journalArticle

Dorman, SE, Goldberg, S, Stout, JE, Muzanyi, G, Johnson, JL, Weiner, MH, Bozeman, L, Heilig, CM, Feng, PJ, Moro, R, Narita, M, Nahid, P, Ray, S, Bates, E, Haile, B, Nuermberger, EL, Vernon, A & Schluger, NW 2012, 'Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis: Study 29 of the tuberculosis trials consortium', Journal of Infectious Diseases, vol. 206, no. 7, pp. 1030-1040. https://doi.org/10.1093/infdis/jis461
Dorman, Susan E. ; Goldberg, Stefan ; Stout, Jason E. ; Muzanyi, Grace ; Johnson, John L. ; Weiner, Marc H ; Bozeman, Lorna ; Heilig, Charles M. ; Feng, Pei Jean ; Moro, Ruth ; Narita, Masahiro ; Nahid, Payam ; Ray, Susan ; Bates, Edward ; Haile, Betial ; Nuermberger, Eric L. ; Vernon, Andrew ; Schluger, Neil W. / Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis : Study 29 of the tuberculosis trials consortium. In: Journal of Infectious Diseases. 2012 ; Vol. 206, No. 7. pp. 1030-1040.
@article{6236ed580ccf4143ad51fbac5f6fd8d0,
title = "Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis: Study 29 of the tuberculosis trials consortium",
abstract = "Background.Rifapentine administered 5 days per week has potent activity in mouse models of antituberculosis chemotherapy, but efficacy and safety data are limited in humans. We compared the antimicrobial activity and safety of rifapentine vs rifampin during the first 8 weeks of pulmonary tuberculosis treatment.Methods.In total, 531 adults with sputum smear-positive pulmonary tuberculosis were randomized to rifapentine 10 mg/kg/dose or rifampin 10 mg/kg/dose, administered 5 days per week for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. Coprimary outcomes were negative sputum culture on liquid and on solid media at completion of intensive phase.Results.Negative cultures on solid media occurred in 145 of 174 participants (83.3) in the rifampin group and 171 of 198 participants (86.4) in the rifapentine group (difference, 3.0; 95 confidence interval [CI]: - 4.3, 10.5); negative cultures in liquid media occurred in 110 of 169 (65.1) in the rifampin group and 133 of 196 (67.9) in the rifapentine group (difference, 2.8; 95 CI: -6.9, 12.4). Among 529 participants who received study therapy, 40 of 254 participants (15.7) in the rifampin group and 40 of 275 participants (14.5) in the rifapentine group prematurely discontinued treatment (P =. 79).Conclusions.The rifapentine regimen was safe but not significantly more active than a standard rifampin regimen, by the surrogate endpoint of culture status at completion of intensive phase. Assessment of higher exposures to rifapentine for tuberculosis treatment is warranted.",
author = "Dorman, {Susan E.} and Stefan Goldberg and Stout, {Jason E.} and Grace Muzanyi and Johnson, {John L.} and Weiner, {Marc H} and Lorna Bozeman and Heilig, {Charles M.} and Feng, {Pei Jean} and Ruth Moro and Masahiro Narita and Payam Nahid and Susan Ray and Edward Bates and Betial Haile and Nuermberger, {Eric L.} and Andrew Vernon and Schluger, {Neil W.}",
year = "2012",
month = "10",
day = "1",
doi = "10.1093/infdis/jis461",
language = "English (US)",
volume = "206",
pages = "1030--1040",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "7",

}

TY - JOUR

T1 - Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis

T2 - Study 29 of the tuberculosis trials consortium

AU - Dorman, Susan E.

AU - Goldberg, Stefan

AU - Stout, Jason E.

AU - Muzanyi, Grace

AU - Johnson, John L.

AU - Weiner, Marc H

AU - Bozeman, Lorna

AU - Heilig, Charles M.

AU - Feng, Pei Jean

AU - Moro, Ruth

AU - Narita, Masahiro

AU - Nahid, Payam

AU - Ray, Susan

AU - Bates, Edward

AU - Haile, Betial

AU - Nuermberger, Eric L.

AU - Vernon, Andrew

AU - Schluger, Neil W.

PY - 2012/10/1

Y1 - 2012/10/1

N2 - Background.Rifapentine administered 5 days per week has potent activity in mouse models of antituberculosis chemotherapy, but efficacy and safety data are limited in humans. We compared the antimicrobial activity and safety of rifapentine vs rifampin during the first 8 weeks of pulmonary tuberculosis treatment.Methods.In total, 531 adults with sputum smear-positive pulmonary tuberculosis were randomized to rifapentine 10 mg/kg/dose or rifampin 10 mg/kg/dose, administered 5 days per week for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. Coprimary outcomes were negative sputum culture on liquid and on solid media at completion of intensive phase.Results.Negative cultures on solid media occurred in 145 of 174 participants (83.3) in the rifampin group and 171 of 198 participants (86.4) in the rifapentine group (difference, 3.0; 95 confidence interval [CI]: - 4.3, 10.5); negative cultures in liquid media occurred in 110 of 169 (65.1) in the rifampin group and 133 of 196 (67.9) in the rifapentine group (difference, 2.8; 95 CI: -6.9, 12.4). Among 529 participants who received study therapy, 40 of 254 participants (15.7) in the rifampin group and 40 of 275 participants (14.5) in the rifapentine group prematurely discontinued treatment (P =. 79).Conclusions.The rifapentine regimen was safe but not significantly more active than a standard rifampin regimen, by the surrogate endpoint of culture status at completion of intensive phase. Assessment of higher exposures to rifapentine for tuberculosis treatment is warranted.

AB - Background.Rifapentine administered 5 days per week has potent activity in mouse models of antituberculosis chemotherapy, but efficacy and safety data are limited in humans. We compared the antimicrobial activity and safety of rifapentine vs rifampin during the first 8 weeks of pulmonary tuberculosis treatment.Methods.In total, 531 adults with sputum smear-positive pulmonary tuberculosis were randomized to rifapentine 10 mg/kg/dose or rifampin 10 mg/kg/dose, administered 5 days per week for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. Coprimary outcomes were negative sputum culture on liquid and on solid media at completion of intensive phase.Results.Negative cultures on solid media occurred in 145 of 174 participants (83.3) in the rifampin group and 171 of 198 participants (86.4) in the rifapentine group (difference, 3.0; 95 confidence interval [CI]: - 4.3, 10.5); negative cultures in liquid media occurred in 110 of 169 (65.1) in the rifampin group and 133 of 196 (67.9) in the rifapentine group (difference, 2.8; 95 CI: -6.9, 12.4). Among 529 participants who received study therapy, 40 of 254 participants (15.7) in the rifampin group and 40 of 275 participants (14.5) in the rifapentine group prematurely discontinued treatment (P =. 79).Conclusions.The rifapentine regimen was safe but not significantly more active than a standard rifampin regimen, by the surrogate endpoint of culture status at completion of intensive phase. Assessment of higher exposures to rifapentine for tuberculosis treatment is warranted.

UR - http://www.scopus.com/inward/record.url?scp=84866135512&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866135512&partnerID=8YFLogxK

U2 - 10.1093/infdis/jis461

DO - 10.1093/infdis/jis461

M3 - Article

VL - 206

SP - 1030

EP - 1040

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 7

ER -