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Volume 31, Number 3—March 2025
CME ACTIVITY - Research

Efficacy and Safety of 4-Month Rifapentine-Based Tuberculosis Treatments in Persons with Diabetes

Ekaterina V. KurbatovaComments to Author , William C. Whitworth, Lakshmi Praveena Peddareddy, Patrick P.J. Phillips, Nigel A. Scott, Kia E. Bryant, Rodney Dawson, Sandra Wagner Cardoso, Wadzanai Samaneka, Melissa Engle, Ziyaad Waja, Erin Sizemore, Wendy Carr, Kelly E. Dooley, Radojka Savic, Susan Swindells, Richard E. Chaisson, Susan E. Dorman, Payam Nahid, Nhung V. Nguyen, and AIDS Clinical Trials Group A5349,1 and Tuberculosis Trials Consortium Study 312
Author affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (E.V. Kurbatova, W.C. Whitworth, L.P. Peddareddy, N.A. Scott, K.E. Bryant, E. Sizemore, W. Carr); University of California– San Francisco Center for Tuberculosis, San Francisco, California, USA (P.P.J. Phillips, R. Savic, P. Nahid); University of Cape Town Lung Institute, Cape Town, South Africa (R. Dawson); Fundação Oswaldo Cruz Insituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil (S. Wagner Cardoso); Milton Park Clinical Research Site, Harare, Zimbabwe (W. Samaneka); Audie L. Murphy Veterans Administration Medical Center, San Antonio, Texas, USA (M. Engle); Wits Health Consortium Perinatal HIV Research Unit, Johannesburg, South Africa (Z. Waja); Vanderbilt University Medical Center, Nashville, Tennessee, USA (K.E. Dooley); University of Nebraska Medical Center, Omaha, Nebraska, USA (S. Swindells); Johns Hopkins University School of Medicine, Baltimore, Maryland, USA (R.E. Chaisson); Medical University of South Carolina, Charleston, South Carolina, USA (S.E. Dorman); Vietnam National Tuberculosis Program/University of California–San Francisco Research Collaboration Unit, Hanoi, Vietnam (N.V. Nguyen)

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Table 2

Safety and tolerability among 178 participants with diabetes (safety analysis population*), by tuberculosis drug regimen, in a study assessing efficacy and safety of 4-month rifapentine-based tuberculosis treatments in persons with diabetes at sites in 12 countries,† January 2016–October 2018‡

Characteristic Control, n = 57 Rifapentine/moxifloxacin, n = 65 Rifapentine, n = 56 Total, N = 178
Primary safety outcome
Participants with grade >3 adverse event, no. (%) 18 (31.6) 15 (23.1) 11 (19.6) 44 (24.7)
Unadjusted risk difference compared with control (95% CI)
–8.7% (–24.5 to 7.1)
 –11.0% (–26.7 to 4.8)
Secondary safety outcome
Participants with treatment-related grade >3 adverse event, no. (%) 4 (7.0) 7 (10.8) 4 (7.1) 15 (8.4)
Unadjusted risk difference compared with control (95% CI)
3.3% (–6.7 to13.2)
 0.5% (–9.2 to 10.1)
Other safety outcomes, no. (%)
Participants with any serious adverse event during treatment 10 (17.5) 7 (10.8) 8 (14.3) 25 (14.0)
Participants who died§ 2 (3.5) 0 0 2 (1.1)
Participants with any adverse event resulting in discontinuation of study treatment¶ 0 4 (6.2) 2 (3.6) 6 (3.4)
Participants with any grade >3 adverse event during 28 weeks after randomization
 18 (31.6)
 19 (29.2)
 13 (23.2)
 50 (28.1)
Liver function test values, no. (%)
ALT or AST >5-fold upper limit of normal# 2 (3.5) 4 (6.2) 2 (3.6) 8 (4.5)
ALT or AST >10-fold upper limit of normal 0 2 (3.1) 2 (3.6) 4 (2.2)
Serum total bilirubin ≥3-fold upper limit of normal** 1 (1.8) 5 (7.7) 3 (5.4) 9 (5.1)
ALT or AST >3-fold upper limit of normal plus serum total bilirubin >2-fold upper limit of normal (Hy’s Law)
 1 (1.8)
 3 (4.6)
 2 (3.6)
 6 (3.4)
Tolerability among microbiologically eligible analysis population, n = 166
Discontinuation of assigned treatment for any reason, no. (%)
 11/57 (19.3)
 8/58 (13.8)
 7/51 (13.7)
 26/166 (15.7)
Unadjusted risk difference compared with control (95% CI) –4.9 (–18.0 to 8.2) –4.7 (–18.4 to 9.0)

*The safety analysis population included all participants who underwent randomization and received >1 dose of the assigned treatment. Safety was assessed during the on-treatment period (the time during which the participants were receiving the study treatment and up to 14 days after the last dose), unless otherwise specified. Adverse events were graded by the site investigators on the basis of the Common Terminology Criteria for Adverse Events criteria, version 4.03 (19). †Brazil, Haiti, India, Kenya, Malawi, Peru, South Africa, Thailand, Uganda, United States, Vietnam, and Zimbabwe. ‡ALT, alanine aminotransferase; AST, aspartate aminotransferase. §In the control regimen group, 2 participants died from pulmonary tuberculosis. ¶In the rifapentine/moxifloxacin regimen group, 4 participants had hepatitis. In the rifapentine regimen group, 2 participants had hepatitis. #ALT or AST >5-fold upper limit of normal corresponds to grade >3. **Total bilirubin >3-fold upper limit of normal corresponds to grade >3.

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1Members of group listed at the end of this article.

2Members of group listed at the end of this article.

Page created: January 15, 2025
Page updated: February 24, 2025
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