Publication date: Dec 02, 2024

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’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, -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. 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.

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