Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia
Creators: name: Collins, Sean P.
name: Strich, Jeffrey R.
name: Iovine, Nicole M.
name: Chen, Peter
name: Gentile, Nina
name: Hager, David N.
name: Shapiro, Nathan
name: Khan, Akram
name: Shotwell, Matthew S.
name: Ginde, Adit A.
name: Harris, Estelle
name: Self, Wesley H.
name: Walsh, Kelly
name: DeClercq, Josh
name: Schrager, Harry
name: Estrada, Vicente
name: Gutiérrez, Felix
name: Safdar, Basmah
name: Sellers, Subhashini
name: Goodwin, Andrew J.
name: Rice, Todd W.
name: Wang, Li
name: de Wit, Marjolein
name: Casey, Jonathan D.
name: Harkins, Michelle
name: Merck, Lisa H.
name: Apodaca, Krystle D.
name: Gibbs, Kevin W.
name: Douglas, Ivor
name: Levitt, Joseph
name: Burgos, Joaquin
name: Files, D. Clark
name: Hudock, Kris
name: Gong, Michelle
name: Schildcrout, Jonathan S.
name: Bernard, Gordon R.
name: Bistran-Hall, Amanda J.
name: Lanspa, Michael
name: Filbin, Michael
name: Semler, Matthew W.
name: Joly, Meghan Morrison
name: Moskowitz, Ari
name: Boyles, Tom
name: Paño-Pardo, Jose R.
name: Sturek, Jeffrey M.
name: Barksdale, Aaron
name: Javaheri, Ali
name: Tiffany, Brian
name: Duggal, Abhijit
name: Desai, Neeraj
name: Hussen, Nazreen
name: Tidswell, Mark A.
name: Pulley, Jill
name: Rosenberg, Yves
name: Troendle, James
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2024

description: <p>Fostamatinib, a spleen tyrosine kinase inhibitor, has been reported to improve outcomes of COVID-19. To evaluate the efficacy and safety of fostamatinib in adults hospitalized with COVID-19 and hypoxemia. 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. Fostamatinib, 150 mg orally twice daily for 14 days, or placebo. The primary outcome was oxygen-free days, an ordinal outcome classifying a participant&rsquo;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. 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, &minus;1.26 days [95% CI, &minus;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. 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. ClinicalTrials.gov Identifier: NCT04924660</p>