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

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