Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis
Susan E Dorman, Payam Nahid, Ekaterina V Kurbatova, Patrick P J Phillips, Kia Bryant, Kelly E Dooley, Melissa Engle, Stefan V Goldberg, Ha T T Phan, James Hakim, John L Johnson, Madeleine Lourens, Neil A Martinson, Grace Muzanyi, Kim Narunsky, Sandy Nerette, Nhung V Nguyen, Thuong H Pham, Samuel Pierre, Anne E Purfield, Wadzanai Samaneka, Radojka M Savic, Ian Sanne, Nigel A Scott, Justin Shenje, Erin Sizemore, Andrew Vernon, Ziyaad Waja, Marc Weiner, Susan Swindells, Richard E Chaisson, AIDS Clinical Trials Group, Tuberculosis Trials Consortium, Harriet Mayanja Kizza, Pheona Nsubuga, Elias Ssaku, Isaac Sekitoleko, Joseph P Akol, Andreas Diacon, Carmen Kleinhans, Julia Sims, Rodney Dawson, Erika Mitchell, Bronwyn Hendricks, Lien T Luu, Hanh T T Nguyen, Hung V Nguyen, Hue T M Nguyen, Cyndy Merrifield, Yvetot Joseph, Marie Jude Jean Louis, Cadette Mercy, Alexandra Apollon, Gertrude Royal, Pamela Mukwekwerere, Yeukai Musodza, Wilfred Gurupira, Michele Tameris, Angelique Kany Kany Luabeya, Mark Hatherill, Mohammed Rassool, Noluthando Mwelase, Jaclyn Bennet, Mario Camblart, Circée Phara Jean, Matebogo Xaba, Maya Jaffer, Keitumetse Majoro, Lerato Mohapi, Ntebo Mogashoa, Debra Peters, Sanjay Gaikwad, Neetal Neverkar, Rahul Lokhande, Cornelius Munyanga, Mina Hosseinipour, Charity Potani, Elisha Okeyo, Samuel Gurrion Ouma, Prisca Rabuogi, Rodrigo Escada, Lidiane Tuler, Johnstone Kumwenda, Kelvin Mponda, Lynne Cornelissen, Andriette Hiemstra, Umesh G Lalloo, Sandy Pillay, Abraham Siika, Kwok-Chiu Chang, Chi Chiu Leung, Alberto Mendoza, Pedro Gonzales, Mey Leon, Javier R Lama, Polo Pavon, Rogelio Duque Jr, Alvaro Schwalb, Eduardo Gotuzzo, George Samuel, Fredrick Sawe, Isaac Tsikhutsu, Sivaporn Gatechompol, Anchalee Avihingsanon, Natthapol Kosashunhanan, Patcharaphan Sugandhavesa, Joseph Burzynski, Mascha Elskamp, Marineide Gonçalves de Melo, Rita de Cassia Alves Lira, Jill Campbell, Marlon Quintero, Elizabeth Guy, Anne Luetkemeyer, Carina Marquez, Kristine Coughlin, Kelly E Dooley, Jacques H Grosset, Eric L Nuermberger, Lara Hosey, Anthony T Podany, Andrey Borisov, Nicole Brown, Deron Burton, Scott Burns, Wendy Carr, Crystal Carter, Lauren Cowan, Melinda Dunn, Barbara DeCausey, Melissa Fagley, Kimberly Hedges, Constance Henderson, Amanda Hott, Carla Jeffries, Katherine Klein, Joan Mangan, Gerald Mazurek, Ruth Moro, Lakshmi Peddareddy, James Posey, Mary Reichler, Jessica Ricaldi, Claire Sadowski, William Whitworth, Melisa Willby, Yan Yuan, April C Pettit, Susan E Dorman, Payam Nahid, Ekaterina V Kurbatova, Patrick P J Phillips, Kia Bryant, Kelly E Dooley, Melissa Engle, Stefan V Goldberg, Ha T T Phan, James Hakim, John L Johnson, Madeleine Lourens, Neil A Martinson, Grace Muzanyi, Kim Narunsky, Sandy Nerette, Nhung V Nguyen, Thuong H Pham, Samuel Pierre, Anne E Purfield, Wadzanai Samaneka, Radojka M Savic, Ian Sanne, Nigel A Scott, Justin Shenje, Erin Sizemore, Andrew Vernon, Ziyaad Waja, Marc Weiner, Susan Swindells, Richard E Chaisson, AIDS Clinical Trials Group, Tuberculosis Trials Consortium, Harriet Mayanja Kizza, Pheona Nsubuga, Elias Ssaku, Isaac Sekitoleko, Joseph P Akol, Andreas Diacon, Carmen Kleinhans, Julia Sims, Rodney Dawson, Erika Mitchell, Bronwyn Hendricks, Lien T Luu, Hanh T T Nguyen, Hung V Nguyen, Hue T M Nguyen, Cyndy Merrifield, Yvetot Joseph, Marie Jude Jean Louis, Cadette Mercy, Alexandra Apollon, Gertrude Royal, Pamela Mukwekwerere, Yeukai Musodza, Wilfred Gurupira, Michele Tameris, Angelique Kany Kany Luabeya, Mark Hatherill, Mohammed Rassool, Noluthando Mwelase, Jaclyn Bennet, Mario Camblart, Circée Phara Jean, Matebogo Xaba, Maya Jaffer, Keitumetse Majoro, Lerato Mohapi, Ntebo Mogashoa, Debra Peters, Sanjay Gaikwad, Neetal Neverkar, Rahul Lokhande, Cornelius Munyanga, Mina Hosseinipour, Charity Potani, Elisha Okeyo, Samuel Gurrion Ouma, Prisca Rabuogi, Rodrigo Escada, Lidiane Tuler, Johnstone Kumwenda, Kelvin Mponda, Lynne Cornelissen, Andriette Hiemstra, Umesh G Lalloo, Sandy Pillay, Abraham Siika, Kwok-Chiu Chang, Chi Chiu Leung, Alberto Mendoza, Pedro Gonzales, Mey Leon, Javier R Lama, Polo Pavon, Rogelio Duque Jr, Alvaro Schwalb, Eduardo Gotuzzo, George Samuel, Fredrick Sawe, Isaac Tsikhutsu, Sivaporn Gatechompol, Anchalee Avihingsanon, Natthapol Kosashunhanan, Patcharaphan Sugandhavesa, Joseph Burzynski, Mascha Elskamp, Marineide Gonçalves de Melo, Rita de Cassia Alves Lira, Jill Campbell, Marlon Quintero, Elizabeth Guy, Anne Luetkemeyer, Carina Marquez, Kristine Coughlin, Kelly E Dooley, Jacques H Grosset, Eric L Nuermberger, Lara Hosey, Anthony T Podany, Andrey Borisov, Nicole Brown, Deron Burton, Scott Burns, Wendy Carr, Crystal Carter, Lauren Cowan, Melinda Dunn, Barbara DeCausey, Melissa Fagley, Kimberly Hedges, Constance Henderson, Amanda Hott, Carla Jeffries, Katherine Klein, Joan Mangan, Gerald Mazurek, Ruth Moro, Lakshmi Peddareddy, James Posey, Mary Reichler, Jessica Ricaldi, Claire Sadowski, William Whitworth, Melisa Willby, Yan Yuan, April C Pettit
Abstract
Background: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis.
Methods: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months.
Results: Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], -2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, -1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, -0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group.
Conclusions: The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.).
Copyright © 2021 Massachusetts Medical Society.
Figures
Source: PubMed