Apixaban for PrOphyLaxis of thromboemboLic Outcomes in COVID-19 (APOLLO)
Primary Purpose
Covid19, Thrombosis
Status
Terminated
Phase
Phase 4
Locations
Brazil
Study Type
Interventional
Intervention
Apixaban 2.5 MG
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Covid19 focused on measuring SARS-CoV2, Anticoagulation, Apixaban
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)
Sites / Locations
- Hospital Maternidade São Vicente de Paulo
- Hospital Israelita Albert Einstein
- Hospital Universitário São Francisco de Assis
- Hospital Santa Paula
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Apixaban Group
Placebo Group
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Hospitalization due to bleeding
Hospitalizations for cardiopulmonary causes
All-cause hospitalization
All-cause death
Days free of venous thromboembolism
Venous thromboembolism (VTE) include deep venous thrombosis and pulmonary embolism.
Major cardiovascular events (MACE)
Major cardiovascular events (MACE) includes cardiovascular death, myocardial infarction (MI) and stroke.
Full Information
NCT ID
NCT04746339
First Posted
February 8, 2021
Last Updated
August 23, 2022
Sponsor
Brazilian Clinical Research Institute
Collaborators
Hospital Israelita Albert Einstein, Hospital do Coracao, Hospital Sirio-Libanes, Hospital Moinhos de Vento, Hospital Alemão Oswaldo Cruz, Beneficência Portuguesa de São Paulo, Brazilian Research In Intensive Care Network
1. Study Identification
Unique Protocol Identification Number
NCT04746339
Brief Title
Apixaban for PrOphyLaxis of thromboemboLic Outcomes in COVID-19
Acronym
APOLLO
Official Title
Apixaban for PrOphyLaxis of thromboemboLic Outcomes in COVID-19 - the Apollo Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why Stopped
Due to the decrease in COVID cases and in the recruitment rate, and DSMB orientation.
Study Start Date
March 4, 2021 (Actual)
Primary Completion Date
May 13, 2022 (Actual)
Study Completion Date
May 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Brazilian Clinical Research Institute
Collaborators
Hospital Israelita Albert Einstein, Hospital do Coracao, Hospital Sirio-Libanes, Hospital Moinhos de Vento, Hospital Alemão Oswaldo Cruz, Beneficência Portuguesa de São Paulo, Brazilian Research In Intensive Care Network
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, Thrombosis
Keywords
SARS-CoV2, Anticoagulation, Apixaban
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
411 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Apixaban Group
Arm Type
Active Comparator
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Apixaban 2.5 MG
Intervention Description
Apixaban 2.5mg twice daily for 30 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo twice daily for 30 days
Primary Outcome Measure Information:
Title
Number of days alive and out of hospital or emergency department
Description
Number of days alive and out of hospital or emergency department through 30 days.
Time Frame
In 30 days
Secondary Outcome Measure Information:
Title
Hospitalization due to bleeding
Time Frame
In 30 days
Title
Hospitalizations for cardiopulmonary causes
Time Frame
In 30 days
Title
All-cause hospitalization
Time Frame
In 30 days
Title
All-cause death
Time Frame
In 30 days
Title
Days free of venous thromboembolism
Description
Venous thromboembolism (VTE) include deep venous thrombosis and pulmonary embolism.
Time Frame
In 30 days
Title
Major cardiovascular events (MACE)
Description
Major cardiovascular events (MACE) includes cardiovascular death, myocardial infarction (MI) and stroke.
Time Frame
In 30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Renato D. Lopes, MD, PhD
Organizational Affiliation
BCRI
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital Maternidade São Vicente de Paulo
City
Barbalha
State/Province
Ceará
Country
Brazil
Facility Name
Hospital Israelita Albert Einstein
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Hospital Universitário São Francisco de Assis
City
Bragança Paulista
State/Province
São Paulo
Country
Brazil
Facility Name
Hospital Santa Paula
City
São Paulo
Country
Brazil
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
Apixaban for PrOphyLaxis of thromboemboLic Outcomes in COVID-19
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