TBTC Study 31: Rifapentine-containing Tuberculosis Treatment Shortening Regimens

Summary

The purpose of this study is to determine whether one or two four-month regimens of tuberculosis treatment are as effective as a standard six-month regimen for treatment of pulmonary tuberculosis (TB). All three regimens are administered daily, seven days each week, with direct observation of each dose by a health-care worker at least five of the seven days of each week. The standard six-month regimen is two months of isoniazid, rifampin, ethambutol, and pyrazinamide followed by four months of isoniazid and rifampin. The first short regimen is a single substitution of rifapentine for rifampin: two months of isoniazid, rifapentine, ethambutol, and pyrazinamide, followed by two months of isoniazid and rifapentine. The second short regimen is a double substitution of rifapentine for rifampin and moxifloxacin for ethambutol: two months of isoniazid, rifapentine, moxifloxacin, and pyrazinamide, followed by two months of isoniazid, rifapentine, and moxifloxacin. Target enrollment is 2500 participants. Each study participant will remain in the study for 18 months in order to include at least 12 months of evaluation of whether the participant's TB recurs.

Timeline

Start

2016-01-25

Primary completion

2020-07

Completion

2021-05

Publications

• Chang VK, Imperial MZ, Phillips PPJ, Velasquez GE, Nahid P, Vernon A, Kurbatova EV, Swindells S, Chaisson RE, Dorman SE, Johnson JL, Weiner M, Jindani A, Harrison T, Sizemore EE, Whitworth W, Carr W, Bryant KE, Burton D, Dooley KE, Engle M, Nsubuga P, Diacon AH, Nhung NV, Dawson R, Savic RM; AIDS Clinical Trial Group; Tuberculosis Trials Consortium. Risk-stratified treatment for drug-susceptible pulmonary tuberculosis. Nat Commun. 2024 Oct 30;15(1):9400. doi: 10.1038/s41467-024-53273-7.
• Xu AY, Velasquez GE, Zhang N, Chang VK, Phillips PPJ, Nahid P, Dorman SE, Kurbatova EV, Whitworth WC, Sizemore E, Bryant K, Carr W, Brown NE, Engle ML, Nhung NV, Nsubuga P, Diacon A, Dooley KE, Chaisson RE, Swindells S, Savic RM. Pyrazinamide Safety, Efficacy, and Dosing for Treating Drug-Susceptible Pulmonary Tuberculosis: A Phase 3, Randomized Controlled Clinical Trial. Am J Respir Crit Care Med. 2024 Dec 1;210(11):1358-1369. doi: 10.1164/rccm.202401-0165OC.
• Ngo HX, Xu AY, Velasquez GE, Zhang N, Chang VK, Kurbatova EV, Whitworth WC, Sizemore E, Bryant K, Carr W, Weiner M, Dooley KE, Engle M, Dorman SE, Nahid P, Swindells S, Chaisson RE, Nsubuga P, Lourens M, Dawson R, Savic RM. Pharmacokinetic-Pharmacodynamic Evidence From a Phase 3 Trial to Support Flat-Dosing of Rifampicin for Tuberculosis. Clin Infect Dis. 2024 Jun 14;78(6):1680-1689. doi: 10.1093/cid/ciae119.
• Kurbatova EV, Phillips PPJ, Dorman SE, Sizemore EE, Bryant KE, Purfield AE, Ricaldi J, Brown NE, Johnson JL, Wallis CL, Akol JP, Ocheretina O, Van Hung N, Mayanja-Kizza H, Lourens M, Dawson R, Nhung NV, Pierre S, Musodza Y, Shenje J, Badal-Faesen S, Vilbrun SC, Waja Z, Peddareddy L, Scott NA, Yuan Y, Goldberg SV, Swindells S, Chaisson RE, Nahid P. A Standardized Approach for Collection of Objective Data to Support Outcome Determination for Late-Phase Tuberculosis Clinical Trials. Am J Respir Crit Care Med. 2023 May 15;207(10):1376-1382. doi: 10.1164/rccm.202206-1118OC.
• Pettit AC, Phillips PPJ, Kurbatova E, Vernon A, Nahid P, Dawson R, Dooley KE, Sanne I, Waja Z, Mohapi L, Podany AT, Samaneka W, Savic RM, Johnson JL, Muzanyi G, Lalloo UG, Bryant K, Sizemore E, Scott N, Dorman SE, Chaisson RE, Swindells S; Tuberculosis Trials Consortium (TBTC) Study 31/AIDS Clinical Trials Group (ACTG) A5349 study team. Rifapentine With and Without Moxifloxacin for Pulmonary Tuberculosis in People With Human Immunodeficiency Virus (S31/A5349). Clin Infect Dis. 2023 Feb 8;76(3):e580-e589. doi: 10.1093/cid/ciac707.
• Podany AT, Pham M, Sizemore E, Martinson N, Samaneka W, Mohapi L, Badal-Faesen S, Dawson R, Johnson JL, Mayanja H, Lalloo U, Whitworth WC, Pettit A, Campbell K, Phillips PPJ, Bryant K, Scott N, Vernon A, Kurbatova EV, Chaisson RE, Dorman SE, Nahid P, Swindells S, Dooley KE, Fletcher CV. Efavirenz Pharmacokinetics and Human Immunodeficiency Virus Type 1 (HIV-1) Viral Suppression Among Patients Receiving Tuberculosis Treatment Containing Daily High-Dose Rifapentine. Clin Infect Dis. 2022 Sep 10;75(4):560-566. doi: 10.1093/cid/ciab1037.
• Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, Engle M, Goldberg SV, Phan HTT, Hakim J, Johnson JL, Lourens M, Martinson NA, Muzanyi G, Narunsky K, Nerette S, Nguyen NV, Pham TH, Pierre S, Purfield AE, Samaneka W, Savic RM, Sanne I, Scott NA, Shenje J, Sizemore E, Vernon A, Waja Z, Weiner M, Swindells S, Chaisson RE; AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis. N Engl J Med. 2021 May 6;384(18):1705-1718. doi: 10.1056/NEJMoa2033400.
• Scott NA, Lee KK, Sadowski C, Kurbatova EV, Goldberg SV, Nsubuga P, Kitshoff R, Whitelaw C, Thuy HN, Batra K, Allen-Blige C, Davis H, Kim J, Phan M, Fedrick P, Chiu KW, Heilig CM, Sizemore E; AIDS Clinical Trials Group and The Tuberculosis Trials Consortium. Optimizing drug inventory management with a web-based information system: The TBTC Study 31/ACTG A5349 experience. Contemp Clin Trials. 2021 Jun;105:106377. doi: 10.1016/j.cct.2021.106377. Epub 2021 Mar 29.
• Bryant KE, Yuan Y, Engle M, Kurbatova EV, Allen-Blige C, Batra K, Brown NE, Chiu KW, Davis H, Elskamp M, Fagley M, Fedrick P, Hedges KNC, Narunsky K, Nassali J, Phan M, Phan H, Purfield AE, Ricaldi JN, Robergeau-Hunt K, Whitworth WC, Sizemore EE; AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Central monitoring in a randomized, open-label, controlled phase 3 clinical trial for a treatment-shortening regimen for pulmonary tuberculosis. Contemp Clin Trials. 2021 May;104:106355. doi: 10.1016/j.cct.2021.106355. Epub 2021 Mar 10.
• Dorman SE, Nahid P, Kurbatova EV, Goldberg SV, Bozeman L, Burman WJ, Chang KC, Chen M, Cotton M, Dooley KE, Engle M, Feng PJ, Fletcher CV, Ha P, Heilig CM, Johnson JL, Lessem E, Metchock B, Miro JM, Nhung NV, Pettit AC, Phillips PPJ, Podany AT, Purfield AE, Robergeau K, Samaneka W, Scott NA, Sizemore E, Vernon A, Weiner M, Swindells S, Chaisson RE; AIDS Clinical Trials Group and the Tuberculosis Trials Consortium. High-dose rifapentine with or without moxifloxacin for shortening treatment of pulmonary tuberculosis: Study protocol for TBTC study 31/ACTG A5349 phase 3 clinical trial. Contemp Clin Trials. 2020 Mar;90:105938. doi: 10.1016/j.cct.2020.105938. Epub 2020 Jan 22.

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Indications