An international clinical trial coordinated by Vanderbilt University Medical Center has revealed that fostamatinib, typically used to treat chronic immune thrombocytopenia, did not significantly improve recovery in hospitalized COVID-19 patients. The randomized, double-blinded, placebo-controlled study, conducted across 62 hospitals between 2021 and 2023, challenges earlier suggestions that the drug could mitigate lung injury and decrease mortality in COVID-19 cases.
The study, published in JAMA Network Open, enrolled 400 adults and assessed the impact of fostamatinib on oxygen-free days, a composite measure of days not requiring supplemental oxygen and survival through day 28. The results indicated that fostamatinib did not significantly increase oxygen-free days compared to the placebo group.
Shift in Patient Demographics
Sean Collins, MD, MSc, professor of Emergency Medicine at VUMC and a lead author of the study, noted a crucial difference in patient characteristics compared to earlier trials. "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," Collins explained. This shift may account for the drug's lack of efficacy in the recent trial.
Matthew Shotwell, PhD, associate professor of Biostatistics and Anesthesiology, and another lead author, highlighted the collaborative nature of the research. "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," Shotwell stated, emphasizing the efficiency gained through the ACTIV-4 platform's design.
ACTIV-4 Host Tissue Platform
The trial was conducted as part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4) Host Tissue platform. This platform investigates potential treatments to prevent life-threatening complications in adults hospitalized with COVID-19, including blood vessel damage, blood clots, and injury to the heart and lungs.
Future Research
Despite the negative findings, researchers are continuing to investigate the mechanisms underlying fostamatinib's effects in COVID-19 patients. Ongoing substudies aim to clarify the impact of patient heterogeneity on treatment outcomes. "Ongoing mechanistic substudies will help us further understand the impact of patient heterogeneity on our results," Collins added.
The ACTIV-4 trials are overseen by the National Heart, Lung, and Blood Institute (NHLBI) and are part of a public-private partnership to accelerate the development of COVID-19 therapeutics.
