1. 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
- Author
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Dorman, Susan E, Nahid, Payam, Kurbatova, Ekaterina V, Goldberg, Stefan V, Bozeman, Lorna, Burman, William J, Chang, Kwok-Chiu, Chen, Michael, Cotton, Mark, Dooley, Kelly E, Engle, Melissa, Feng, Pei-Jean, Fletcher, Courtney V, Ha, Phan, Heilig, Charles M, Johnson, John L, Lessem, Erica, Metchock, Beverly, Miro, Jose M, Nhung, Nguyen Viet, Pettit, April C, Phillips, Patrick PJ, Podany, Anthony T, Purfield, Anne E, Robergeau, Kathleen, Samaneka, Wadzanai, Scott, Nigel A, Sizemore, Erin, Vernon, Andrew, Weiner, Marc, Swindells, Susan, Chaisson, Richard E, and Consortium, The AIDS Clinical Trials Group and the Tuberculosis Trials
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Lung ,Tuberculosis ,HIV/AIDS ,Infectious Diseases ,Orphan Drug ,Sexually Transmitted Infections ,Rare Diseases ,Clinical Research ,Clinical Trials and Supportive Activities ,Emerging Infectious Diseases ,6.1 Pharmaceuticals ,5.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adolescent ,Adult ,Female ,Humans ,Male ,Middle Aged ,Young Adult ,Antitubercular Agents ,Directly Observed Therapy ,Drug Administration Schedule ,Drug Therapy ,Combination ,Equivalence Trials as Topic ,Ethambutol ,HIV Infections ,Moxifloxacin ,Rifampin ,Tuberculosis ,Pulmonary ,Multicenter Studies as Topic ,Clinical Trials ,Phase III as Topic ,TB ,Multicenter randomized trial ,Non-inferiority ,Rifapentine ,AIDS Clinical Trials Group and the Tuberculosis Trials Consortium ,Medical and Health Sciences ,General Clinical Medicine ,Public Health ,Biomedical and clinical sciences ,Health sciences - Abstract
IntroductionPhase 2 clinical trials of tuberculosis treatment have shown that once-daily regimens in which rifampin is replaced by high dose rifapentine have potent antimicrobial activity that may be sufficient to shorten overall treatment duration. Herein we describe the design of an ongoing phase 3 clinical trial testing the hypothesis that once-daily regimens containing high dose rifapentine in combination with other anti-tuberculosis drugs administered for four months can achieve cure rates not worse than the conventional six-month treatment regimen.Methods/designS31/A5349 is a multicenter randomized controlled phase 3 non-inferiority trial that compares two four-month regimens with the standard six-month regimen for treating drug-susceptible pulmonary tuberculosis in HIV-negative and HIV-positive patients. Both of the four-month regimens contain high-dose rifapentine instead of rifampin, with ethambutol replaced by moxifloxacin in one regimen. All drugs are administered seven days per week, and under direct observation at least five days per week. The primary outcome is tuberculosis disease-free survival at twelve months after study treatment assignment. A total of 2500 participants will be randomized; this gives 90% power to show non-inferiority with a 6.6% margin of non-inferiority.DiscussionThis phase 3 trial formally tests the hypothesis that augmentation of rifamycin exposures can shorten tuberculosis treatment to four months. Trial design and standardized implementation optimize the likelihood of obtaining valid results. Results of this trial may have important implications for clinical management of tuberculosis at both individual and programmatic levels.Trial registrationNCT02410772. Registered 8 April 2015,https://www.clinicaltrials.gov/ct2/show/NCT02410772?term=02410772&rank=1.
- Published
- 2020