tetano
Editor, Senior Moderator
JAMA Netw Open
. 2024 Dec 2;7(12):e2448215.
doi: 10.1001/jamanetworkopen.2024.48215. Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia: A Randomized Clinical Trial
Sean P Collins[SUP] 1 2 [/SUP], Matthew S Shotwell[SUP] 3 [/SUP], Jeffrey R Strich[SUP] 4 [/SUP], Kevin W Gibbs[SUP] 5 [/SUP], Marjolein de Wit[SUP] 6 [/SUP], D Clark Files[SUP] 5 [/SUP], Michelle Harkins[SUP] 7 [/SUP], Kris Hudock[SUP] 8 [/SUP], Lisa H Merck[SUP] 9 [/SUP], Ari Moskowitz[SUP] 10 [/SUP], Krystle D Apodaca[SUP] 7 [/SUP], Aaron Barksdale[SUP] 11 [/SUP], Basmah Safdar[SUP] 12 [/SUP], Ali Javaheri[SUP] 13 [/SUP], Jeffrey M Sturek[SUP] 14 [/SUP], Harry Schrager[SUP] 15 [/SUP], Nicole M Iovine[SUP] 16 [/SUP], Brian Tiffany[SUP] 17 [/SUP], Ivor Douglas[SUP] 18 [/SUP], Joseph Levitt[SUP] 19 [/SUP], Adit A Ginde[SUP] 20 [/SUP], David N Hager[SUP] 21 [/SUP], Nathan Shapiro[SUP] 22 [/SUP], Abhijit Duggal[SUP] 23 [/SUP], Akram Khan[SUP] 24 [/SUP], Michael Lanspa[SUP] 25 [/SUP], Peter Chen[SUP] 26 [/SUP], Nina Gentile[SUP] 27 [/SUP], Estelle Harris[SUP] 28 [/SUP], Michelle Gong[SUP] 29 [/SUP], Subhashini Sellers[SUP] 30 [/SUP], Andrew J Goodwin[SUP] 31 [/SUP], Mark A Tidswell[SUP] 32 [/SUP], Michael Filbin[SUP] 33 [/SUP], Neeraj Desai[SUP] 34 [/SUP], Felix Gutiérrez[SUP] 35 [/SUP], Vicente Estrada[SUP] 36 [/SUP], Joaquin Burgos[SUP] 37 [/SUP], Tom Boyles[SUP] 38 [/SUP], Jose R Paño-Pardo[SUP] 39 [/SUP], Nazreen Hussen[SUP] 40 [/SUP], Yves Rosenberg[SUP] 41 [/SUP], James Troendle[SUP] 41 [/SUP], Gordon R Bernard[SUP] 42 43 [/SUP], Amanda J Bistran-Hall[SUP] 43 [/SUP], Kelly Walsh[SUP] 43 [/SUP], Jonathan D Casey[SUP] 42 [/SUP], Josh DeClercq[SUP] 3 [/SUP], Meghan Morrison Joly[SUP] 43 [/SUP], Jill Pulley[SUP] 43 [/SUP], Todd W Rice[SUP] 42 43 [/SUP], Jonathan S Schildcrout[SUP] 3 [/SUP], Li Wang[SUP] 3 [/SUP], Matthew W Semler[SUP] 42 [/SUP], Wesley H Self[SUP] 1 43 [/SUP]; ACTIV-4 Host Tissue Investigators
Collaborators, Affiliations
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.
. 2024 Dec 2;7(12):e2448215.
doi: 10.1001/jamanetworkopen.2024.48215. Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia: A Randomized Clinical Trial
Sean P Collins[SUP] 1 2 [/SUP], Matthew S Shotwell[SUP] 3 [/SUP], Jeffrey R Strich[SUP] 4 [/SUP], Kevin W Gibbs[SUP] 5 [/SUP], Marjolein de Wit[SUP] 6 [/SUP], D Clark Files[SUP] 5 [/SUP], Michelle Harkins[SUP] 7 [/SUP], Kris Hudock[SUP] 8 [/SUP], Lisa H Merck[SUP] 9 [/SUP], Ari Moskowitz[SUP] 10 [/SUP], Krystle D Apodaca[SUP] 7 [/SUP], Aaron Barksdale[SUP] 11 [/SUP], Basmah Safdar[SUP] 12 [/SUP], Ali Javaheri[SUP] 13 [/SUP], Jeffrey M Sturek[SUP] 14 [/SUP], Harry Schrager[SUP] 15 [/SUP], Nicole M Iovine[SUP] 16 [/SUP], Brian Tiffany[SUP] 17 [/SUP], Ivor Douglas[SUP] 18 [/SUP], Joseph Levitt[SUP] 19 [/SUP], Adit A Ginde[SUP] 20 [/SUP], David N Hager[SUP] 21 [/SUP], Nathan Shapiro[SUP] 22 [/SUP], Abhijit Duggal[SUP] 23 [/SUP], Akram Khan[SUP] 24 [/SUP], Michael Lanspa[SUP] 25 [/SUP], Peter Chen[SUP] 26 [/SUP], Nina Gentile[SUP] 27 [/SUP], Estelle Harris[SUP] 28 [/SUP], Michelle Gong[SUP] 29 [/SUP], Subhashini Sellers[SUP] 30 [/SUP], Andrew J Goodwin[SUP] 31 [/SUP], Mark A Tidswell[SUP] 32 [/SUP], Michael Filbin[SUP] 33 [/SUP], Neeraj Desai[SUP] 34 [/SUP], Felix Gutiérrez[SUP] 35 [/SUP], Vicente Estrada[SUP] 36 [/SUP], Joaquin Burgos[SUP] 37 [/SUP], Tom Boyles[SUP] 38 [/SUP], Jose R Paño-Pardo[SUP] 39 [/SUP], Nazreen Hussen[SUP] 40 [/SUP], Yves Rosenberg[SUP] 41 [/SUP], James Troendle[SUP] 41 [/SUP], Gordon R Bernard[SUP] 42 43 [/SUP], Amanda J Bistran-Hall[SUP] 43 [/SUP], Kelly Walsh[SUP] 43 [/SUP], Jonathan D Casey[SUP] 42 [/SUP], Josh DeClercq[SUP] 3 [/SUP], Meghan Morrison Joly[SUP] 43 [/SUP], Jill Pulley[SUP] 43 [/SUP], Todd W Rice[SUP] 42 43 [/SUP], Jonathan S Schildcrout[SUP] 3 [/SUP], Li Wang[SUP] 3 [/SUP], Matthew W Semler[SUP] 42 [/SUP], Wesley H Self[SUP] 1 43 [/SUP]; ACTIV-4 Host Tissue Investigators
Collaborators, Affiliations
- PMID: 39625722
- PMCID: PMC11615712
- DOI: 10.1001/jamanetworkopen.2024.48215
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.