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.
Drug: Apixaban 2.5 MG
Apixaban 2.5mg twice daily for 30 days
Drug: Placebo
placebo twice daily for 30 days
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)
Hospital Maternidade São Vicente de Paulo
Barbalha, Ceará, Brazil
Hospital Israelita Albert Einstein
São Paulo, SP, Brazil
Hospital Universitário São Francisco de Assis
Bragança Paulista, São Paulo, Brazil
Hospital Santa Paula
São Paulo, Brazil
Renato D. Lopes, MD, PhD, Study Chair
BCRI