Apixaban for PrOphyLaxis of thromboemboLic Outcomes in COVID-19

Apixaban for PrOphyLaxis of thromboemboLic Outcomes in COVID-19 - the Apollo Trial

Randomized, double-blinded, placebo-controlled trial comparing oral anticoagulation with placebo for community-dwelling patients with symptomatic COVID-19 infection and risk factors for thrombosis.

Randomized, double-blinded, placebo-controlled trial comparing oral anticoagulation with placebo for community-dwelling patients with symptomatic COVID-19 infection and risk factors for thrombosis.

Randomization 1:1 - Group 1 will receive Apixaban 2.5mg twice daily vs. matching placebo (Group 2) for 30 days.

Primary Objective: To evaluate the clinical impact of a strategy of oral anticoagulation with apixaban comparing with placebo on the number of days alive and out of the hospital/emergency department (DAOH) through 30 days in outpatients with symptomatic SARS-CoV2 infection and risk factors for thrombosis.

Inclusion Criteria:

• Outpatients with symptomatic laboratory-proven diagnosis of COVID-19 (any exam that shows acute infection as positive PCR or IgM in a context of acute symptoms ≤ 10 days) AND

• Negative pregnancy test for women in child bearing period AND

• D-dimer level ≥ 2x ULN or

• C-reactive protein (CRP) ≥ 10 mg/L or

• At least two of the following risk factors:

  • d-dimer level ≥ULN
  • CRP ≥ULN
  • age ≥65,
  • diabetes,
  • chronic kidney disease stage 3
  • cardiopulmonary disease (for example, peripheral arterial disease, coronary artery disease, heart failure, chronic obstructive pulmonary disease),
  • history of PE/DVT,
  • nursing home/SNF resident or severely restricted mobility
  • Body mass index ≥30 kg/m2.

Exclusion Criteria:

• Age < 18 years-old
• Patients with indication for full anticoagulation during inclusion (for example, diagnosis of venous thromboembolism, atrial fibrillation, mechanical valve prosthesis)
• Platelets < 50,000 /mm3
• Use of acetylsalicylic acid > 100 mg per day
• Use of P2Y12 inhibitor (clopidogrel, prasugrel, ticagrelor)
• Chronic use of NSAIDs
• Hypersensitivity to apixaban
• Creatinine clearance < 30 ml/min
• Pregnancy or breastfeeding
• Patients contraindicated to anticoagulation (active bleeding, recent major surgery, blood dyscrasia or prohibitive hemorrhage risk as evaluated by the investigator)
• 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
• 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)