Details
The U.S. Food and Drug Administration (FDA) initiated this study to explore Sentinel’s ability to provide data on the real-world occurrence of thrombotic events in adult patients with COVID-19. FDA intended for these data to inform design decisions, such as sample size estimates, for two National Heart, Lung, and Blood Institute (NHLBI)-funded clinical trials (Accelerating COVID-19 Therapeutic Interventions and Vaccines 4, also known as ACTIV-4) that investigated the efficacy and safety of antithrombotic therapy in preventing thrombotic events in COVID-19 patients in the inpatient and outpatient care settings.
FDA conducted analyses in the outpatient and inpatient care settings using the TriNetX Live™ platform. Among 89,640 adult patients not hospitalized at the time of COVID-19 identification (outpatient analysis) and without evidence of pre-existing risk factors for thrombosis, 0.6% experienced hospitalized thrombotic events or death within 45 days. Only approximately 5% of these COVID-19 patients had relevant laboratory data (C-reactive protein, D-dimer) that was used in clinical trial inclusion criteria.
Among 23,580 hospitalized COVID-19 patients (inpatient analysis), 5.5% experienced a thrombotic event or death within 28 days, a significantly lower frequency of thrombotic events compared with those reported in published literature. Almost half (46.2%) had a D-dimer laboratory result within 3 days, and event rates were similar for patients regardless of D-dimer level (elevated=5.6%, normal=6.4%). The study also aimed to assess the outcome of “free from organ support” but there were substantial challenges in identifying some components of this outcome, particularly oxygen support.
The results of this analysis supported FDA’s public health response to COVID-19. This analysis provided supplemental data to the NHLBI Collaborative Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (CONNECTS) steering and executive committees regarding the thrombotic event rates to support their sample size calculations for the outpatient ACTIV-4 trial.