COVID-19 Thrombosis Prevention Trials: Post-hospital Thromboprophylaxis

NCT ID: NCT04650087

Last Updated: 2025-02-25

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1291 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-15

Study Completion Date

2022-09-23

Brief Summary

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A multicenter, adaptive, randomized platform trial evaluating the efficacy and safety of antithrombotic strategies in patients with COVID-19 following hospital discharge

Detailed Description

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This study is an adaptive, prospective, randomized platform trial designed to compare the effectiveness and safety of antithrombotic therapy with no antithrombotic therapy after hospitalization for 48 hours or longer for COVID-19. For Stage 1 of this study, participants will be randomized to either prophylactic anticoagulation or matching placebo for 30 days, and then followed for an additional 60 days after the completion of treatment (total duration of follow-up, 90 days).

The primary objective is to determine the most effective and safe antithrombotic strategy to prevent the composite outcome of symptomatic deep vein thrombosis, pulmonary embolism, other venous thromboembolism, ischemic stroke, myocardial infarction, other arterial thromboembolism, and all-cause mortality by 30 days following discharge from the hospital.

Biobanking of samples for future biomarker and mechanistic studies will be available for centers able to participate and collect samples from eligible participants. Samples will be collected at the time of enrollment and after the completion of 30 days of therapy

Conditions

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Covid19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double Blind

Study Groups

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Apixaban

Drug: Apixaban 2.5 MG Participants will be given study medication at the time of discharge from the hospital. Participants will take Apixaban 2.5 MG twice a day, once in the morning and once in the evening, for 30 days. Participants will be contacted (electronic or telephone) 2 days after starting the study medication and contact will continue up to day 90 after starting study treatment. Follow up will be through electronic and/or telephone contact depending on the participant's preference, compliance, and medication adherence. Participants will be queried for any clinically relevant endpoints, especially major bleeding or a need to seek healthcare attention for any reason. Follow-up will occur from the time of discharge and through the 30 day study period, with contacts 2 days, 10 days, 20 days, and 30 days after discharge. Two additional study contacts will take place 45 days and 90 days after discharge.

Group Type ACTIVE_COMPARATOR

Apixaban 2.5 MG

Intervention Type DRUG

Participants will take Apixaban 2.5 MG twice a day, once in the morning and once in the evening for 30 days. Participants will be contacted (electronic or telephone) 2 days after starting the study medication and will continue up to day 90 after starting study treatment. Followup will occur from the time of discharge through the 30 day study period with contacts at 2 days, 10 days, 20 days and 30 days after discharge. Two additional study contacts will take place 45 days and 90 days after discharge.

Placebo

Drug: Placebo Participants will be given study medication at the time of discharge from the hospital. Participants will take the Placebo twice a day, once in the morning and once in the evening, for 30 days. Participants will be contacted (electronic or telephone) 2 days after starting the study medication and contact will continue up to day 90 after starting study treatment. Follow up will be through electronic and/or telephone contact depending on the participant's preference, compliance, and medication adherence. Participants will be queried for any clinically relevant endpoints, especially major bleeding or a need to seek healthcare attention for any reason. Follow-up will occur from the time of discharge and through the 30 day study period, with contacts 2 days, 10 days, 20 days, and 30 days after discharge. Two additional study contacts will take place 45 days and 90 days after discharge.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants will take placebo twice a day, once in the morning and once in the evening for 30 days. Participants will be contacted (electronic or telephone) 2 days after starting the study medication and will continue up to day 90 after starting study treatment. Followup will occur from the time of discharge through the 30 day study period with contacts at 2 days, 10 days, 20 days and 30 days after discharge. Two additional study contacts will take place 45 days and 90 days after discharge.

Interventions

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Apixaban 2.5 MG

Participants will take Apixaban 2.5 MG twice a day, once in the morning and once in the evening for 30 days. Participants will be contacted (electronic or telephone) 2 days after starting the study medication and will continue up to day 90 after starting study treatment. Followup will occur from the time of discharge through the 30 day study period with contacts at 2 days, 10 days, 20 days and 30 days after discharge. Two additional study contacts will take place 45 days and 90 days after discharge.

Intervention Type DRUG

Placebo

Participants will take placebo twice a day, once in the morning and once in the evening for 30 days. Participants will be contacted (electronic or telephone) 2 days after starting the study medication and will continue up to day 90 after starting study treatment. Followup will occur from the time of discharge through the 30 day study period with contacts at 2 days, 10 days, 20 days and 30 days after discharge. Two additional study contacts will take place 45 days and 90 days after discharge.

Intervention Type DRUG

Other Intervention Names

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Eliquis

Eligibility Criteria

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Inclusion Criteria

* • Age ≥ 18 years

* PCR-positive COVID-19 infection
* Hospitalized for two or more days

Exclusion Criteria

* Pre-existing indication for anticoagulation (e.g., pulmonary embolism or deep vein thrombosis; atrial fibrillation; mechanical cardiac valve)
* Contraindication to antithrombotic therapy (e.g., known bleeding within the last 30 days requiring emergency room presentation or hospitalization; major surgery within 14 days; ischemic stroke, intracranial bleed or neurosurgery within 3 months.
* Platelet count \< 50,000/mcL
* Hemoglobin \<8 gm/dL
* Renal insufficiency (eGFR \< 30 mL/min/1.73 m2)
* Pregnancy
* Prison inmate
* Life expectancy less than 90 days
* Unwilling or unable to provide informed consent/unwilling or unable to complete the study protocol
* Dual antiplatelet therapy that cannot be discontinued
* Concomitant need for strong inducers/inhibitors of p-gp or CYP3A4
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Thomas L. Ortel

OTHER

Sponsor Role lead

Responsible Party

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Thomas L. Ortel

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Tracy Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

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Valleywise Health Medical Center

Phoenix, Arizona, United States

Site Status

Dignity Health-St Josephs

Phoenix, Arizona, United States

Site Status

Central Arkansas Veterans Health Care System

Little Rock, Arkansas, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Stanford University School of Medicine

Palo Alto, California, United States

Site Status

UCSF at Zuckerberg San Francisco General Hospital

San Francisco, California, United States

Site Status

New Ananda Medical and Urgent Care, Inc.

South El Monte, California, United States

Site Status

Mazur and Statner MD PC

Thousand Oaks, California, United States

Site Status

Torrance Medical Center

Torrance, California, United States

Site Status

Centura Health Porter Adventist Hospital

Denver, Colorado, United States

Site Status

Saint Anthony Hospital

Lakewood, Colorado, United States

Site Status

St. Anthony North Health Campus

Westminster, Colorado, United States

Site Status

Baycare Hospital

Clearwater, Florida, United States

Site Status

Florida Heart Center

Ft. Pierce, Florida, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

Tallahassee Memorial HealthCare

Tallahassee, Florida, United States

Site Status

James A. Haley Veteran's Hospital

Tampa, Florida, United States

Site Status

BayCare Hospital- Winter Haven

Winter Haven, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Medical College of Georgia/Augusta University

Augusta, Georgia, United States

Site Status

Savannah Health Services, LLC DBA Memorial Health University Medical Center

Savannah, Georgia, United States

Site Status

Queens Medical Center

Honolulu, Hawaii, United States

Site Status

Hawaii Pacific Health

Honolulu, Hawaii, United States

Site Status

Snake River Research, PLLC

Idaho Falls, Idaho, United States

Site Status

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status

Cook County Health

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

The University of Chicago Medicine

Chicago, Illinois, United States

Site Status

OSF Little Company of Mary

Evergreen Park, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Indiana University Health Bloomington Hospital

Bloomington, Indiana, United States

Site Status

Lutheran Medical Group

Fort Wayne, Indiana, United States

Site Status

Indiana University Health Methodist Hospital

Indianapolis, Indiana, United States

Site Status

Franciscan Health Michigan City

Michigan City, Indiana, United States

Site Status

Reid Physician Associates

Richmond, Indiana, United States

Site Status

Baptist Health Lexington

Lexington, Kentucky, United States

Site Status

University Medical Center New Orleans

New Orleans, Louisiana, United States

Site Status

Ochsner Clinic Foundation-Baton Rouge

New Orleans, Louisiana, United States

Site Status

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Willis-Knighton Physician Network/Tri-State Medical Clinic

Shreveport, Louisiana, United States

Site Status

Maine Medical Center/Maine Medical Partners Adult Hospital Medicine

Portland, Maine, United States

Site Status

Pen Bay Medical Center

Rockport, Maine, United States

Site Status

Anne Arundel Medical Center

Annapolis, Maryland, United States

Site Status

Lifebridge (Sinai Hospital of Baltimore)

Baltimore, Maryland, United States

Site Status

Adventist HealthCare Shady Grove Medical Center

Rockville, Maryland, United States

Site Status

Boston University

Boston, Massachusetts, United States

Site Status

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Site Status

Baystate Medical center

Springfield, Massachusetts, United States

Site Status

Bay Regional Medical Center d/b/a/ McLaren Bay Region

Bay City, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Western Michigan University

Kalamazoo, Michigan, United States

Site Status

MidMichigan Medical Center

Midland, Michigan, United States

Site Status

McLaren Macomb

Mount Clemens, Michigan, United States

Site Status

Minneapolis VA Health Care System

Minneapolis, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Truman Medical Center

Kansas City, Missouri, United States

Site Status

Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

St Louis University

St Louis, Missouri, United States

Site Status

Mercury Street Medical Group

Butte, Montana, United States

Site Status

CHI St Elizabeth Hospital

Lincoln, Nebraska, United States

Site Status

Renown Health

Reno, Nevada, United States

Site Status

Dartmouth Hichcock Medical Center

Lebanon, New Hampshire, United States

Site Status

AtlantiCare Regional Medical Center

Atlantic City, New Jersey, United States

Site Status

Hope Tower at Jersey Shore University Medical Center

Neptune City, New Jersey, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

Capital Health System, Inc.

Trenton, New Jersey, United States

Site Status

Christus St. Vincent Regional Medical Center

Santa Fe, New Mexico, United States

Site Status

NYU Langone Hospital-Brooklyn

Brooklyn, New York, United States

Site Status

Coney Island Hospital

Brooklyn, New York, United States

Site Status

Buffalo General Medical Center

Buffalo, New York, United States

Site Status

Mercy Hospital Buffalo

Buffalo, New York, United States

Site Status

Jamaica Hospital Medical Center

Jamaica, New York, United States

Site Status

New York University Langone Health

New York, New York, United States

Site Status

Stony Brook University Hospital

Stony Brook, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Westchester Medical Center

Valhalla, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Duke Medical Center

Durham, North Carolina, United States

Site Status

East Carolina University/Vidant Health

Greenville, North Carolina, United States

Site Status

Wake Med Hospital

Raleigh, North Carolina, United States

Site Status

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Summa Health

Akron, Ohio, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Kettering Medical Center

Kettering, Ohio, United States

Site Status

Ascension St. John Bartlesville

Tulsa, Oklahoma, United States

Site Status

Ascension St. John Tulsa

Tulsa, Oklahoma, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

St. Luke's University Health Network

Easton, Pennsylvania, United States

Site Status

Conemaugh Memorial Medical Center

Johnstown, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Tower Health Medical Group

West Reading, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

The Miriam Hospital

Providence, Rhode Island, United States

Site Status

Monument Health Clinical Research

Rapid City, South Dakota, United States

Site Status

Erlanger Health System

Chattanooga, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Christus St. Elizabeth Hospital

Beaumont, Texas, United States

Site Status

Baylor Scott and White Medical Center- College Station

College Station, Texas, United States

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University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Texas Health Harris Methodist

Fort Worth, Texas, United States

Site Status

University of Texas- Houston, LBJ Hospital

Houston, Texas, United States

Site Status

UT Houston MHH-SW

Houston, Texas, United States

Site Status

UTHouston

Houston, Texas, United States

Site Status

Texas Health Frisco

Plano, Texas, United States

Site Status

Baylor Scott and White-Round Rock

Round Rock, Texas, United States

Site Status

Baylor Scott and White-Temple

Temple, Texas, United States

Site Status

The Woodlands Center For Respiratory & Sleep Research

The Woodlands, Texas, United States

Site Status

CHRISTUS Trinity Clinic Pulmonary Medicine

Tyler, Texas, United States

Site Status

The University of Texas Health Science Center at Tyler

Tyler, Texas, United States

Site Status

UT Health East Texas (Tyler)

Tyler, Texas, United States

Site Status

UT Rio Grande Valley

Weslaco, Texas, United States

Site Status

MultiCare Institute for Research & Innovation

Puyallup, Washington, United States

Site Status

UW Medicine Valley Medical Center

Renton, Washington, United States

Site Status

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

CAMC Clinical Trials Center

Charleston, West Virginia, United States

Site Status

West Virginia University Hospital

Morgantown, West Virginia, United States

Site Status

Blood Center of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Santos BC, Flumignan RL, Civile VT, Atallah AN, Nakano LC. Prophylactic anticoagulants for non-hospitalised people with COVID-19. Cochrane Database Syst Rev. 2023 Aug 16;8(8):CD015102. doi: 10.1002/14651858.CD015102.pub2.

Reference Type DERIVED
PMID: 37591523 (View on PubMed)

Wang TY, Wahed AS, Morris A, Kreuziger LB, Quigley JG, Lamas GA, Weissman AJ, Lopez-Sendon J, Knudson MM, Siegal DM, Kasthuri RS, Alexander AJ, Wahid L, Atassi B, Miller PJ, Lawson JW, Patel B, Krishnan JA, Shapiro NL, Martin DE, Kindzelski AL, Leifer ES, Joo J, Lyu L, Pennella A, Everett BM, Geraci MW, Anstrom KJ, Ortel TL; ACTIV-4C Study Group. Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization. Ann Intern Med. 2023 Apr;176(4):515-523. doi: 10.7326/M22-3350. Epub 2023 Mar 21.

Reference Type DERIVED
PMID: 36940444 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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Pro00107078

Identifier Type: -

Identifier Source: org_study_id

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