@article{ef4af59a8c3f49fdba42a4737d8ce813,
title = "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",
abstract = "Introduction: Phase 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/Design: S31/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. Discussion: This 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 registration:NCT02410772. Registered 8 April 2015,https://www.clinicaltrials.gov/ct2/show/NCT02410772?term=02410772&rank=1",
keywords = "Moxifloxacin, Multicenter randomized trial, Non-inferiority, Rifapentine, TB, Tuberculosis",
author = "{The AIDS Clinical Trials Group and the Tuberculosis Trials Consortium} and Dorman, {Susan E.} and Payam Nahid and Kurbatova, {Ekaterina V.} and Goldberg, {Stefan V.} and Lorna Bozeman and Burman, {William J.} and Chang, {Kwok Chiu} and Michael Chen and Mark Cotton and Dooley, {Kelly E.} and Melissa Engle and Feng, {Pei Jean} and Fletcher, {Courtney V.} and Phan Ha and Heilig, {Charles M.} and Johnson, {John L.} and Erica Lessem and Beverly Metchock and Miro, {Jose M.} and Nhung, {Nguyen Viet} and Pettit, {April C.} and Phillips, {Patrick P.J.} and Podany, {Anthony T.} and Purfield, {Anne E.} and Kathleen Robergeau and Wadzanai Samaneka and Scott, {Nigel A.} and Erin Sizemore and Andrew Vernon and Marc Weiner and Susan Swindells and Chaisson, {Richard E.}",
note = "Funding Information: Supported by the United States Centers for Disease Control and Prevention (CDC), the Tuberculosis Trials Consortium (TBTC) collaborates on this trial with the AIDS Clinical Trials Group (ACTG) network, supported by the United States National Institutes of Health . Existing sites from these two networks completed standard startup requirements. Sites submitted detailed descriptions of procedures for direct observation of treatment (DOT) and mycobacteriology laboratory testing. Recruitment occurred in Brazil, Haiti, Hong Kong, India, Kenya, Malawi, Peru, South Africa, Thailand, Uganda, the United States, Vietnam and Zimbabwe ( Fig. 2 ); the socio-demographic characteristics of study participants are expected generally to represent those populations most affected by tuberculosis worldwide. Funding Information: Funding support for this trial was provided by the U.S. Centers for Disease Control and Prevention , National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention , Division of Tuberculosis Elimination; and by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Numbers UM1 AI068634 , UM1 AI068636 and UM1 AI106701 . Funding Information: Supported by the United States Centers for Disease Control and Prevention (CDC), the Tuberculosis Trials Consortium (TBTC) collaborates on this trial with the AIDS Clinical Trials Group (ACTG) network, supported by the United States National Institutes of Health. Existing sites from these two networks completed standard startup requirements. Sites submitted detailed descriptions of procedures for direct observation of treatment (DOT) and mycobacteriology laboratory testing. Recruitment occurred in Brazil, Haiti, Hong Kong, India, Kenya, Malawi, Peru, South Africa, Thailand, Uganda, the United States, Vietnam and Zimbabwe (Fig. 2); the socio-demographic characteristics of study participants are expected generally to represent those populations most affected by tuberculosis worldwide.Funding support for this trial was provided by the U.S. Centers for Disease Control and Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Division of Tuberculosis Elimination; and by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Numbers UM1 AI068634, UM1 AI068636 and UM1 AI106701. Publisher Copyright: {\textcopyright} 2020",
year = "2020",
month = mar,
doi = "10.1016/j.cct.2020.105938",
language = "English (US)",
volume = "90",
journal = "Contemporary Clinical Trials",
issn = "1551-7144",
publisher = "Elsevier Inc.",
}