Full Anticoagulation Versus Prophylaxis in COVID-19: COALIZAO ACTION Trial

Randomized Clinical Trial to Evaluate a Routine Full Anticoagulation Strategy in Patients With Coronavirus (COVID-19) - COALIZAO ACTION Trial

Pragmatic randomized clinical trial of patients admitted to the hospital with confirmed COVID-19 infection and elevated D-Dimer.

Randomization 1:1 - Group 1 will undergo a routine full anticoagulation (oral or parenteral when needed) strategy; and group 2 will receive usual standard of care with prophylactic anticoagulation

Patients admitted to hospital with confirmed COVID-19, and who meet the eligibility criteria will be invited to participate in the proposed study. Following the application of the informed consent form, they will collect the D-dimer (if they have not yet collected it routinely from the hospital) and confirm the value over the normal limit in patients with confirmed COVID-19, will be randomized to 2 groups in the 1:1 ratio. Group 1 will follow the strategy of routine use of full anticoagulation therapy (oral or parenteral when indicated); and group 2 will follow the usual standard care with in-hospital prophylactic anticoagulation (without routine full anticoagulation).

Inclusion Criteria:

• Patients with confirmed diagnosis of COVID-19 admitted to hospital;
• Duration of symptoms related to hospitalization ≤ 14 days;
• Patients ≥ 18 year old;
• D-dimer above the upper limit of normal (collected until 72 hours before the randomization);
• Agreement to participate by providing the informed consent form (ICF).

Exclusion Criteria:

• Patients with indication for full anticoagulation during inclusion (for example, diagnosis of venous thromboembolism, atrial fibrillation, mechanical valve prosthesis);
• Platelets < 50,000 /mm3
• Need for ASA therapy > 100 mg;
• Need for P2Y12 inhibitor therapy (clopidogrel, ticagrelor or prasugrel);
• Chronic use of non-hormonal anti-inflammatory drugs;
• Sustained uncontrolled systolic blood pressure (BP) of ≥180 mmHg or diastolic BP of ≥100 mmHg;
• INR > 1,5;
• Patients contraindicated to full anticoagulation (active bleeding, liver failure, blood dyscrasia or prohibitive hemorrhage risk as evaluated by the investigator);
• Criteria for disseminated intravascular coagulation (DIC);
• A history of hemorrhagic stroke or any intracranial bleeding at any time in the past or current intracranial neoplasm (benign or malignant), cerebral metastases, arteriovenous (AV) malformation, or aneurysm;
• Active cancer (excluding non-melanoma skin cancer) defined as cancer not in remission or requiring active chemotherapy or adjunctive therapies such as immunotherapy or radiotherapy;
• Hypersensitivity to rivaroxaban;
• Use of strong inhibitors of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein (P-gp) (e.g. protease inhibitors, ketoconazole, Itraconazole) and/or use of P-gp and strong CYP3A4 inducers (such as but not limited to rifampin/rifampicin, rifabutin, rifapentine, phenytoin, phenobarbital, carbamazepine, or St. John's Wort);
• Known HIV infection;
• Creatinine clearance < 30 ml/min according to the Cockcroft-Gault Formula;
• Pregnancy or breastfeeding.