Apixaban for PrOphyLaxis of thromboemboLic Outcomes in COVID-19

Phase 4

Terminated

• Conditions: Covid19; Thrombosis
• Interventions: Drug: Apixaban 2.5 MG; Drug: Placebo

• Registration Number: NCT04746339
• Lead Sponsor: Brazilian Clinical Research Institute

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-02-08
• Study First Submitted QC: 2021-02-08
• Study First Posted: 2021-02-09
• Study Start: 2021-03-04
• Primary Completion: 2022-05-13
• Study Completion: 2022-05-30
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-23
• Last Update Posted: 2022-08-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 411

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Apixaban Group	Apixaban 2.5 MG	-
Placebo Group	Placebo	-

Primary Outcome Measures

Name	Time	Method
Number of days alive and out of hospital or emergency department	In 30 days	Number of days alive and out of hospital or emergency department through 30 days.

Secondary Outcome Measures

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

Trial Locations

Locations (4)

Hospital Maternidade São Vicente de Paulo; 🇧🇷 Barbalha, Ceará, Brazil

Hospital Universitário São Francisco de Assis; 🇧🇷 Bragança Paulista, São Paulo, Brazil

Hospital Israelita Albert Einstein; 🇧🇷 São Paulo, SP, Brazil

Hospital Santa Paula; 🇧🇷 São Paulo, Brazil