Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia

作者：Sean P. Collins, Matthew S. Shotwell, Jeffrey R. Strich, Kevin W. Gibbs, Marjolein de Wit, D. Clark Files, Michelle Harkins, Kristin Hudock, Lisa H. Merck, Ari Moskowitz, Krystle D. Apodaca, Aaron Barksdale, Basmah Safdar, Ali Javaheri, Jeffrey M. Sturek, Harry Schrager, Nicole M. Iovine, Brian Tiffany, Ivor S. Douglas, Joseph E. Levitt, Adit A. Ginde, David N. Hager, Nathan I. Shapiro, Abhijit Duggal, Akram Khan, Michael J. Lanspa, Peter Chen, Nina Gentile, Estelle S. Harris, Michelle N. Gong, Subhashini A. Sellers, Andrew Goodwin, Mark Tidswell, Michael R. Filbin, Neeraj Desai, Félix Gutiérrez, Vicente Estrada, Joaquín Burgos, Tom Boyles, José Ramón Paño‐Pardo, Nazreen Hussen, Yves Rosenberg, James Troendle, Gordon R. Bernard, Amanda J. Bistran-Hall, Kelly Walsh, Jonathan D. Casey, Josh DeClercq, Meghan M. Joly, Jill M. Pulley, Todd W. Rice, Jonathan S. Schildcrout, Li Wang, Matthew W. Semler, Wesley H. Self, ACTIV-4 Host Tissue Investigators, Richard C. Becker, Gregory del Zoppo, Peter K. Henke, Richard Holubkov, Maryl R. Johnson, Kim M. Kerr, Hannah I. Lipman, Fedor Lurie, Bertram Pitt, Sara K. Vesely, Jerome L. Fleg, Dave Aamodt, Debra Clark, Jessica Collins, Sheri Dixon, Maya Cook, Carly Gatewood, John Graves, Debbie Hunter, Courtney Jordan, Seungbeom Ko, Ugo Lekqauwa, Itzel Lopez, David McKeel, Dirk Orozco, Nelson Prato, Ally Qi, Kalley Stagner, Krista Vermillion, Stephanie Winchell, Taylor Young, Esteban Masuda, Asif Siddiqui, Caroline Brooks, Carl Fletcher, Annie Duffy, Paul Walsh, Jack Moody, T Sobande, Amina Ali, Y. Henry, Frances Ogueri, Alba Sierto, Maria Sanchez Grande, Chiara Spinello, O. W. Anthony, Michael E. Sieracki, Michaella Tomlin, Anton Pozniak, Tim Leaver, P.C. Parks, Jakea Johnson, Ryan Walsh, Brian Bales, Karen Miller, Donna Torr, Clark Files, Kevin W. Gibbs, Darija Ward, Leigha Landreth, Lisa Parks, Lori Flores, J. Pedro Teixeira, Sandra Cárdenas, Juan A. Ceniceros, Amy G. Cunningham, Susan Kunkel, Debbie M. Lovato, Brooklin Zimmerman, Thanh N. Nguyen, Wesley Zeger, Noah Wiedel, Stephanie Stilinovic, Caroline Foster, Jeanne Flannigan, Carolyn Brokowski, Jing Lü, Muriel J. Solberg, Dana Lee, Brian Tiffany, Charlotte Tanner, Annette K. Taylor, Jennine Zumbahl, Aamer Syed, Jessica Mason, Patrick Jackson, Rachael Coleman, Heather M. Haughey, Kartikeya Cherabuddi, Rebecca Wakeman, Kathryn Fairbank-Haynes, Angela J. Rogers, Jennifer G. Wilson, Rosemary Vojnik, Cynthia Pérez, David Wyles, Terra Hiller, Judy Oakes, Ana Z. Garcia, Flora Martinez, Jennifer Fickes-Siler, David J. Douin, Amiran Baduashvili, Henry Kramer, Lakshmi Chauhan, Amanda Martinez, Jennifer Peers, Kristine Schauer, Lani Finck, Jill Bastman, Ashley Licursi, Sharon Hayes, Nicholas Kurtzman, Elinita Rosseto, Douglas Scaffidi, Nathan I. Shapiro, Jonathan Pak, Gopal Allada, Genesis Briceño, José D. Torres‐Peña, Minn Oh, Michelle Gong, Amira Mohamed, Luke Andrea, Rahul Nair, William Nkemdirim, Sabah Boujid, Martha Torres, Ofelia Garcı́a, Harith Ali, Sasha Beselman, Yolanda Eby, V. N. Klimov, R. Duncan Hite, Hammad Tanzeem, Chris Droege, Jessica O. Winter, Simon Mucha, Nirosshan Thiruchelvam, Matthew Siuba, Omar Mehkri, Susan Jackman, Antonina Caudill, Emad Bayoumi, Ethan Pascual, Po-En Chen, Sam Torbati, Tanyalak Parimon, Bradley T. Rosen, Yuri Matusov, Michael J. Lanspa, Ithan D. Peltan, Samuel M. Brown, Jason Carr, Daniel Knox, Lindsay Leither, Brenda López, Benjamin Galen, Nina Gentile, Derek Isenberg, Hannah Reimer, Paul Cincola, Estelle S. Harris, Sean J. Callahan, Misty B. Yamane, Macy A G Barrios, Neeraj Desai, Amit Bharara, Michael Keller, Prat Majumder, Carrie Dohe, Kathryn A. Hibbert, Justin Margolin, Blair A. Parry, Mark Tidswell, Jay S. Steingrub, Lesley De Souza, Cynthia Kardos, Denise Gallant, Rae Lynn DeFoe, S Romain, Scott Ouellette, Serena Estrada, Ryan Kindle, Bogdan Tiru, Howard Smithline, Carolyn García, Charles Terry, Melissa Blender, Abbey Grady, Andrew Powell, Peter C. Hou, Mohammad Adrian Hasdianda, Seven E. Miyawaki, Mikita Umale, Valeria D Cantos, Colleen F. Kelley, Paulina A. Rebolledo, Sheetal Kandiah, Renee Cook, Betsy Hall, Christin Root, Juliet Brown, Christopher Foster, Philip Powers, Pamela Lankford-Turner, Bela Patel, Rodeo Abrencillo, Robier Anguillon-Prada, Ryan Huebinger, Gabriel Patarroyo‐Aponte, Syed Ghazi Rizvi, Elizabeth Vidales, Idorenyin Udoh-Bradford, Mar Masiá, Sergio Padilla, Guillermo Telenti, Paula Mascarell, Javier García‐Abellán, Ángela Botella, Catalina Robledano, Vicente Estrada, Reynaldo Homen, Javier Rodríguez-Añover, Joaquin Burgos, Tom Boyles, Zanele Mkhabela, Galadriel Pellejero, Elena Morte-Romea, Santiago Letona-Carbajo, María José Esquillor, Carla Toyas, Silvia Loscos, Nazreen Hussen, Carlos Guijarro, María Velasco, Esaú Custódio João Filho, Ênio Pereira de Souza, Christoph Boesecke, Jürgen K. Rockstroh, Marco Ripa, Silvia Nozza · 发表于：JAMA Network Open · 年份：2024 · DOI：10.1001/jamanetworkopen.2024.48215 · 被引用次数：9 · 研究领域：COVID-19 Clinical Research Studies、Heparin-Induced Thrombocytopenia and Thrombosis、Long-Term Effects of COVID-19

Importance: Fostamatinib, a spleen tyrosine kinase inhibitor, has been reported to improve outcomes of COVID-19. Objective: To evaluate the efficacy and safety of fostamatinib in adults hospitalized with COVID-19 and hypoxemia. Design, Setting, and Participants: This multicenter, phase 3, placebo-controlled, double-blinded randomized clinical trial was conducted at 41 US sites and 21 international sites between November 17, 2021, and September 27, 2023; the last follow-up visit was December 31, 2023. Participants were adults aged 18 years or older hospitalized with acute SARS-CoV-2 infection and hypoxemia. Data were analyzed between January 10 and March 8, 2024. Interventions: Fostamatinib, 150 mg orally twice daily for 14 days, or placebo. Main Outcomes and Measures: The primary outcome was oxygen-free days, an ordinal outcome classifying a participant's status at day 28 based on mortality and duration of supplemental oxygen use. An adjusted odds ratio (AOR) greater than 1.0 was considered to indicate superiority of fostamatinib over placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included elevated transaminase values, neutropenia, and hypertension. Results: Of the 400 participants randomized (median age, 67 years [IQR, 58-76 years]; 210 [52.5%] men), 199 received fostamatinib and 201 received placebo. The mean (SD) number of oxygen-free days was 13.4 (12.4) in the fostamatinib group and 14.2 (12.1) in the placebo group (unadjusted mean diffe...