Apixaban for PrOphyLaxis of thromboemboLic Outcomes in COVID-19 (APOLLO)

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.

Study Overview

• Status: Terminated
• Conditions: Covid19; Thrombosis
• Intervention / Treatment: Drug: Apixaban 2.5 MG; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 411
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil
    • Hospital Santa Paula
  • Ceará
    • Barbalha, Ceará, Brazil
      • Hospital Maternidade São Vicente de Paulo
  • SP
    • São Paulo, SP, Brazil
      • Hospital Israelita Albert Einstein
  • São Paulo
    • Bragança Paulista, São Paulo, Brazil
      • Hospital Universitário São Francisco de Assis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Group	Drug: Placebo; placebo twice daily for 30 days
Active Comparator: Apixaban Group	Drug: Apixaban 2.5 MG; Apixaban 2.5mg twice daily for 30 days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brazilian Clinical Research Institute
• Collaborators: Hospital Israelita Albert Einstein; Hospital Moinhos de Vento; Hospital do Coracao; Hospital Sirio-Libanes; Hospital Alemão Oswaldo Cruz; Beneficência Portuguesa de São Paulo; Brazilian Research In Intensive Care Network
• Investigators: Study Chair: Renato D. Lopes, MD, PhD, BCRI

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2021
• Primary Completion (Actual): May 13, 2022
• Study Completion (Actual): May 30, 2022

Study Registration Dates

• First Submitted: February 8, 2021
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Actual): August 25, 2022
• Last Update Submitted That Met QC Criteria: August 23, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Anticoagulation; SARS-CoV2; Apixaban
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Embolism and Thrombosis; COVID-19; Thrombosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Apixaban
• Other Study ID Numbers: 004/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All data provided during study is anonymized to respect the privacy of patients who have participated in the trial in line with applicable regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No