Clinical trials of anticoagulation in COVID-19: a systematic review
A high prevalence of thrombotic events is observed in coronavirus-2019 (COVID-19). Optimal anticoagulation becomes a critical part of treatment and higher-dose prophylactic anticoagulation is being practiced. Prospective evidence to confirm the safety and efficacy of these regimens is lacking. We performed a systematic review of existing studies of anticoagulation in COVID-19. The ClinicalTrials.gov registry, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the EU Clinical Trials Register (EudraCT) were searched from inception to September 1, 2020. PRISMA guidelines were followed. Qualitative and quantitative analysis were performed. We identified 36 clinical studies involving anticoagulation in COVID-19. Most common study location was the United States (n=12, 33%). Thirty studies were randomized-controlled (83%) of which 22 were open-label. Median sample size was 309 (IQR 139-952) and study duration was 233 days (IQR 174-357). Most common study setting was critical and non-critical care (n=21, 58%). Most common single primary outcome was all-cause mortality (n=15, 42%) but thrombotic events represent the overall most common primary outcome (n=28, 77%). Low molecular weight heparin (LMWH) was the most common agent studied (n=25, 69%) followed by unfractionated heparin (UFH) (n=14, 38.8%) and factor Xa antagonists (n=8, 22.2%). Therapeutic-intensity prophylaxis was the most common dosage regimen studied in comparison to routine thromboprophylaxis dose in 76% and 86% of studies with LMWH and UFH respectively. Five studies (14%) used intermediate-dose prophylaxis. Bleeding is studied as an outcome variable in 19 studies (53%). Our review identifies studies of anticoagulation in COVID-19 and the pharmacological agents used, dosage intensities, and the outcomes analyzed.
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