Randomized Clinical Trial to Evaluate a Routine Full Anticoagulation Strategy in Patients with Coronavirus Infection (SARS-CoV2) Admitted to Hospital: Rationale and Design of the ACTION (AntiCoagulaTlon cOroNavirus)-Coalition IV Trial.



Observational studies have suggested a higher risk of thrombotic events in patients with coronavirus disease 2019 (COVID-19). Moreover, elevated D-dimer levels have been identified as an important prognostic marker in COVID-19 directly associated with disease severity and progression. Prophylactic anticoagulation for hospitalized COVID-19 patients might not be enough to prevent thrombotic events; therefore, therapeutic anticoagulation regimens deserve clinical investigation.


ACTION is an academic-led, pragmatic, multicenter, open-label, randomized, phase IV clinical trial that aims to enroll around 600 patients at 40 sites participating in the Coalition COVID-19 Brazil initiative. Eligible patients with a confirmed diagnosis of COVID-19 with symptoms up to 14 days and elevated D-dimer levels will be randomized to a strategy of full-dose anticoagulation for 30 days with rivaroxaban 20 mg once daily (or full-dose heparin if oral administration is not feasible) versus standard of care with any approved venous thromboembolism (VTE) prophylaxis regimen during hospitalization. A confirmation of COVID-19 was mandatory for study entry, based on specific tests used in clinical practice (RT-PCR, antigen test, IgM test) collected before randomization, regardless of in the outpatient setting or not. Randomization will be stratified by clinical stability at presentation. The primary outcome is a hierarchical analysis of mortality, length of hospital stay, or duration of oxygen therapy at the end of 30 days. Secondary outcomes include the World Health Organization's 8-point ordinal scale at 30 days and the following individual efficacy outcomes: incidence of VTE, acute myocardial infarction, stroke, systemic embolism, major adverse limb events, duration of oxygen therapy, disease progression, and biomarkers. The primary safety outcomes are major or clinically relevant non-major bleeding according to the International Society on Thrombosis and Haemostasis criteria.


The ACTION trial will evaluate whether in-hospital therapeutic anticoagulation with rivaroxaban for stable patients, or enoxaparin for unstable patients, followed by rivaroxaban through 30 days compared with standard prophylactic anticoagulation improves clinical outcomes in hospitalized patients with COVID-19 and elevated D-dimer levels. CLINICALTRIALS.GOV: : NCT04394377.





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Publication Info

Lopes, Renato D, Pedro Gabriel Melo de Barros E Silva, Remo HM Furtado, Ariane Vieira Scarlatelli Macedo, Eduardo Ramacciotti, Lucas Petri Damini, Bruna Bronhara, Alexandre B Cavalcanti, et al. (2021). Randomized Clinical Trial to Evaluate a Routine Full Anticoagulation Strategy in Patients with Coronavirus Infection (SARS-CoV2) Admitted to Hospital: Rationale and Design of the ACTION (AntiCoagulaTlon cOroNavirus)-Coalition IV Trial. American heart journal. 10.1016/j.ahj.2021.04.005 Retrieved from https://hdl.handle.net/10161/22859.

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John Hunter Peel Alexander

Professor of Medicine

John H. Alexander, MD, MHS is a cardiologist and Professor of Medicine in the Department of Medicine, Division of Cardiology at Duke University School of Medicine, as well as the Vice Chief, Clinical Research in the Division of Cardiology. He is the Director of Cardiovascular Research at the Duke Clinical Research Institute where he oversees a large group of clinical research faculty and a broad portfolio of cardiovascular clinical trials and observational clinical research programs. He is a member of the American Society of Clinical Investigation.

Dr. Alexander’s clinical interests are in acute and general cardiovascular disease, valvular heart disease, and echocardiology. His research is focused on the translation of novel therapeutic concepts into clinical data through clinical trials, specifically on the therapeutics of acute coronary syndromes, chronic coronary artery disease, and cardiac surgery and on novel methodological approaches to clinical trials. He was on the Executive Committee of the ARISTOTLE trial of apixaban in patients with atrial fibrillation and was the Principal Investigator of the APPRAISE-2 trial of apixaban in patients with acute coronary syndromes.

Dr. Alexander has published extensively and has served as the principal investigator of numerous multicenter clinical trials. He currently serves as the co-chair of the Clinical Trial Transformation Initiative (CTTI).

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