An international trial coordinated by Vanderbilt University Medical Center suggests that fostamatinib, a treatment for the blood disorder chronic immune thrombocytopenia, did not significantly decrease oxygen-free days or improve outcomes for hospitalized patients with COVID-19.
Previous studies suggested that fostamatinib may suppress inflammatory responses triggered by COVID-19 and mitigate ongoing lung injury, decreasing mortality and oxygen requirements.
In the randomized, double-blinded placebo-controlled clinical trial of 400 adults conducted between 2021 and 2023 at 62 hospitals, including 21 outside the United States, fostamatinib did not significantly decrease the number of oxygen-free days, a composite of days on supplemental oxygen and/or mortality through study day 28, compared to a control group.
Results were reported in the journal JAMA Network Open. The paper’s lead authors were VUMC’s Sean Collins, MD, MSc, professor of Emergency Medicine, and Matthew Shotwell, PhD, associate professor of Biostatistics and Anesthesiology, and Jeffrey Strich, MD, of the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.
“These results suggest fostamatinib does not improve recovery from COVID-19 infection,” said Collins, director of the VUMC Center for Emergency Care Research and Innovation. “While this may be due to a lack of fostamatinib efficacy, there was a significant change in patient characteristics between the original trials and ours.
“Patients enrolled in prior trials were young, unvaccinated and otherwise healthy. Those enrolled in our study were older, vaccinated and had multiple comorbidities including chronic lung disease. Ongoing mechanistic substudies will help us further understand the impact of patient heterogeneity on our results.”
The study was part of the three-trial Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4) Host Tissue platform, which investigated fostamatinib and two experimental medications aimed at preventing potentially life-threatening complications, including blood vessel damage, blood clots and injury to the heart and lungs, in adults hospitalized with COVID-19.
“The three trials in the platform shared a placebo group, which reduced the total number of participants required to complete all three trials by more than 150,” said Shotwell, principal investigator of the platform’s Data Coordinating Center. “In total, 899 participants were enrolled across all three trials.”
Collins holds the Clinical Directorship for Emergency Medicine Research. Other VUMC co-authors were Gordon Bernard, MD, Amanda Bistran-Hall, Kelly Walsh, BSN, Jonathan Casey, MD, MSCI, Josh DeClercq, MS, Meghan Morrison Joly, PhD, Jill Pulley, MBA, Todd Rice, MD, Jonathan Schildcrout, PhD, Matthew Semler, MD, Li Wang, MS, and senior author Wesley Self, MD, MPH.
Also contributing to this work were research staff of the Vanderbilt Coordinating Center, the VUMC Department of Biostatistics, the European treatment network for HIV, hepatitis and global emerging infectious diseases, Research Organization (KC) Ltd, and pharmaceutical industry partners.
Part of a public-private partnership of research protocols, the ACTIV-4 trials were overseen by the NHLBI. This study was supported in part by NIH grant OT2HL156812.
