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 language | English (US) |
|---|---|
| Pages (from-to) | 1030-1040 |
| Number of pages | 11 |
| Journal | Journal of Infectious Diseases |
| Volume | 206 |
| Issue number | 7 |
| DOIs | |
| State | Published - Oct 1 2012 |
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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 journal › Article
}
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
C2 - 22850121
AN - SCOPUS:84866135512
VL - 206
SP - 1030
EP - 1040
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 7
ER -