On 4 September, 2020, the US National Institutes of Health launched a new clinical trial, “A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic and Additional Strategies in Hospitalized Adults with COVID-19.” This open-label, placebo-controlled, multicenter, adaptive platform study was designed to evaluate therapeutic options for patients hospitalized with mild, moderate, or severe COVID-19. A variety of drugs and drug classes were selected, including heparin, the monoclonal antibody crizanlizumab, sodium-glucose cotransporter-2 inhibitors, and purinergic signaling receptor Y₁₂ inhibitors. These medications have been widely used in the treatment of other conditions, from sick cell disease to type 2 diabetes mellitus and some forms of cardiovascular disease, but their inclusion in a study of COVID-19 was somewhat unexpected. This article examines the rationale behind the use of these disparate agents in the treatment and prevention of adverse outcomes in patients with COVID-19 and explores how these strategies may be utilized in the future to address the severe acute respiratory syndrome coronavirus 2 pandemic.