Clinical trial NCT04746339: Apixaban for PrOphyLaxis of thromboemboLic Outcomes in COVID-19
Official title: Apixaban for PrOphyLaxis of thromboemboLic Outcomes in COVID-19 - the Apollo Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Covid19
Thrombosis
Keywords: SARS-CoV2
Anticoagulation
Apixaban
Lead sponsor: Brazilian Clinical Research Institute
Sponsor class: OTHER
Collaborators: name: Hospital Israelita Albert Einstein
name: Hospital do Coracao
name: Hospital Sirio-Libanes
name: Hospital Moinhos de Vento
name: Hospital Alemão Oswaldo Cruz
name: Beneficência Portuguesa de São Paulo
name: Brazilian Research In Intensive Care Network
First posted: 2021-02-09
Enrollment: 411
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of days alive and out of hospital or emergency department
timeFrame: In 30 days
Secondary outcomes:
measure: Hospitalization due to bleeding
timeFrame: In 30 days
measure: Hospitalizations for cardiopulmonary causes
timeFrame: In 30 days
measure: All-cause hospitalization
timeFrame: In 30 days
measure: All-cause death
timeFrame: In 30 days
measure: Days free of venous thromboembolism
timeFrame: In 30 days
measure: Major cardiovascular events (MACE)
timeFrame: In 30 days
Other outcomes:
Locations:
city: Barbalha
country: Brazil
facility: Hospital Maternidade São Vicente de Paulo
state: Ceará
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
state: SP
city: Bragança Paulista
country: Brazil
facility: Hospital Universitário São Francisco de Assis
state: São Paulo
city: São Paulo
country: Brazil
facility: Hospital Santa Paula
Study officials:
affiliation: BCRI
name: Renato D. Lopes, MD, PhD
role: STUDY_CHAIR
References: