Apixaban for PrOphyLaxis of thromboemboLic Outcomes in COVID-19

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Covid19, Thrombosis

Intervention / Treatment
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* Drug: Apixaban 2.5 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Apixaban Group<br> | Drug: Apixaban 2.5 MG<br>* Apixaban 2.5mg twice daily for 30 days<br>|
| Placebo Comparator: Placebo Group<br> | Drug: Placebo<br>* placebo twice daily for 30 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days alive and out of hospital or emergency department | Number of days alive and out of hospital or emergency department through 30 days. | In 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospitalization due to bleeding |  | In 30 days | 
| Hospitalizations for cardiopulmonary causes |  | In 30 days | 
| All-cause hospitalization |  | In 30 days | 
| All-cause death |  | In 30 days | 
| Days free of venous thromboembolism | Venous thromboembolism (VTE) include deep venous thrombosis and pulmonary embolism. | In 30 days | 
| Major cardiovascular events (MACE) | Major cardiovascular events (MACE) includes cardiovascular death, myocardial infarction (MI) and stroke. | In 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV2, Anticoagulation, Apixaban