Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia
Authors: Sean P. Collins, Matthew S. Shotwell, Jeffrey R. Strich, Kevin W. Gibbs, Marjolein de Wit, D. Clark Files, Michelle Harkins, Kris 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 Douglas, Joseph Levitt, Adit A. Ginde, David N. Hager, Nathan Shapiro, Abhijit Duggal, Akram Khan, Michael Lanspa, Peter Chen, Nina Gentile, Estelle Harris, Michelle Gong, Subhashini Sellers, Andrew J. Goodwin, Mark A. Tidswell, Michael Filbin, Neeraj Desai, Felix Gutiérrez, Vicente Estrada, Joaquin Burgos, Tom Boyles, Jose R. Paño-Pardo, Nazreen Hussen, Yves Rosenberg, James Troendle, Gordon R. Bernard, Amanda J. Bistran-Hall, Kelly Walsh, Jonathan D. Casey, Josh DeClercq, Meghan Morrison Joly, Jill Pulley, Todd W. Rice, Jonathan S. Schildcrout, Li Wang, Matthew W. Semler, Wesley H. Self, Richard C. Becker, Gregory del Zoppo, Peter Henke, Richard Holubkov, Maryl Johnson, Kim Kerr, Hannah I. Lipman, Fedor Lurie, Bertram Pitt, Sara K. Vesely, Jerome L. Fleg, Dave Aamodt, Debra Clark, Jessica B. Collins, Sheri Dixon, Maya Cook, Carly Gatewood, John Graves, Debbie Hunter, Courtney Jordan, Sahar Ko, Ugo (Ben) 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, Toni Sobande, Amina Ali, Yomi Henry, Frances Ogueri, Alba Sierto, Maria Sanchez Grande, Chiara Spinello, Olufunke Anthony, Michal Sieracki, Michaella Tomlin, Anton Pozniak, Tim Leaver, Polly Parks, Jakea Johnson, Ryan Walsh, Brian Bales, Karen Miller, Donna Torr, Clark Files, Kevin Gibbs, Darija Ward, Leigha Landreth, Lisa Parks, Lori Flores, J. Pedro Teixeira, Sandra Cardenas, Juan A. Ceniceros, Amy G. Cunningham, Susan Kunkel, Debbie M. Lovato, Brooklin Zimmerman, Thanh Nguyen, Wesley Zeger, Noah Wiedel, Stephanie Stilinovic, Caroline Foster, Jeanne Flannigan, Carolyn Brokowski, Jing Lu, Muriel Solberg, Dana Lee, Brian Tiffany, Charlotte Tanner, Annette Taylor, Jennine Zumbahl, Aamer Syed, Jessica Mason, Patrick E. H. Jackson, Rachael W. Coleman, Heather M. Haughey, Kartik Cherabuddi, Rebecca Wakeman, Kathryn Fairbank-Haynes, Angela J. Rogers, Jennifer G. Wilson, Rosemary Vojnik, Cynthia Perez, David Wyles, Terra D. Hiller, Judy L. 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 Shapiro, Jonathan Pak, Gopal Allada, Genesis Briceno, Jose Peña, Minn Oh, Michelle Gong, Amira Mohamed, Luke Andrea, Rahul Nair, William Nkemdirim, Sabah Boujid, Martha Torres, Ofelia Garcia, Harith Ali, Sasha Beselman, Yolanda Eby, Vitaliy Klimov, R. Duncan Hite, Hammad Tanzeem, Chris Droege, Jessica Winter, Simon Mucha, Nirosshan Thiruchelvam, Matthew Siuba, Omar Mehkri, Susan Jackman, Antonina Caudill, Emad Bayoumi, Ethan Pascual, Po-En Chen, Sam S. Torbati, Tanyalak Parimon, Bradley Rosen, Yuri Matusov, Michael J. Lanspa, Ithan D. Peltan, Samuel M. Brown, Jason R. Carr, Daniel B. Knox, Lindsay M. Leither, Brenda Lopez, Benjamin Galen, Nina Gentile, Derek Isenberg, Hannah Reimer, Paul Cincola, Estelle S. Harris, Sean J. Callahan, Misty B. Yamane, Macy AG Barrios, Neeraj Desai, Amit Bharara, Michael Keller, Prat Majumder, Carrie Dohe, Kathryn Hibbert, Justin Margolin, Blair Parry, Mark A. Tidswell, Jay S. Steingrub, Lesley De Souza, Cynthia Kardos, Denise Gallant, Rae Lynn DeFoe, Sara Romain, Scott Ouellette, Serena Estrada, Ryan Kindle, Bogdan Tiru, Howard Smithline, Carolyn Garcia, Charles Terry, Melissa Blender, Abbey Grady, Andrew Powell, Peter C. Hou, Mohammad A. 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, Vincente Estrada, Reynaldo Homen, Javier Rodriguez-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, Maria Velasco-Arribas, Esaú Custódio João Filho, Elaine C. de Oliveira Souza, Christoph Boesecke, Jurgen Rockstroh, Marco Ripa, Silvia Nozza
Journal: JAMA Network Open (2024)

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 difference, −1.26 days [95% CI, −3.52 to 1.00 days]; AOR, 0.82 [95% credible interval (CrI), 0.58-1.17]). Mortality at 28 days occurred in 22 of 195 patients (11.3%) in the fostamatinib group and 16 of 197 (8.1%) in the placebo group (AOR, 1.44; 95% CrI, 0.72-2.90). Aspartate aminotransferase elevation occurred more commonly in the fostamatinib group (23 [11.6%]) than in the placebo group (11 [5.5%]; AOR, 2.28; 95% CrI, 1.07-4.84). Other safety outcomes were similar between groups. Conclusions and Relevance In this randomized clinical trial of adults hospitalized with COVID-19 and hypoxemia, fostamatinib did not increase the number of oxygen-free days compared with placebo. These results do not support the hypothesis that fostamatinib improves outcomes among adults hospitalized with hypoxemia during the Omicron era. Trial Registration ClinicalTrials.gov Identifier: NCT04924660