In collaboration with the National Heart, Lung, and Blood Institute, Operation Warp Speed, the US Food and Drug Administration, and as part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, the 3 of us have been asked to lead nationwide randomized clinical trials of anticoagulant and antithrombotic therapies to improve clinical outcomes among coronavirus disease 2019 (COVID-19)–infected inpatients and outpatients and those convalescing from the disease. Known collectively as ACTIV-4 Antithrombotics, the need for these trials is clear because life-threatening deep vein thromboses, pulmonary emboli, systemic arterial thromboses, and microvascular thromboses occur commonly in patients with COVID-19, even among those who appear otherwise minimally symptomatic.

Lacking trial data, cardiologists caring for patients with COVID-19 have little guidance on how to proceed with thrombosis prevention and, as a result, are using a wide variety of interventions, none of which has been tested in trials of adequate sample size. Is the best choice of treatment for patients acutely ill with COVID-19 requiring hospitalization unfractionated or low-molecular-weight heparin? If so, at what dose should this medication be administered, or should alternative agents be considered? For patients being discharged after hospitalization for COVID-19, should anticoagulation be continued, and if so, for how long and can a simple oral regimen such as prophylactic-dose apixaban be used? For patients with COVID-19

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