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

ImportanceFostamatinib, a spleen tyrosine kinase inhibitor, has been reported to improve outcomes of COVID-19.ObjectiveTo evaluate the efficacy and safety of fostamatinib in adults hospitalized with COVID-19 and hypoxemia.Design, Setting, and ParticipantsThis 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.InterventionsFostamatinib, 150 mg orally twice daily for 14 days, or placebo.Main Outcomes and MeasuresThe 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.ResultsOf 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 RelevanceIn 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 RegistrationClinicalTrials.gov Identifier: NCT04924660