NCT04650087

Brief Summary

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,291

participants targeted

Target at P75+ for phase_3 covid19

Timeline
Completed

Started Feb 2021

Longer than P75 for phase_3 covid19

Geographic Reach
1 country

121 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 30, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 2, 2020

Completed
3 months until next milestone

Study Start

First participant enrolled

February 15, 2021

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 24, 2022

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 23, 2022

Completed
2.4 years until next milestone

Results Posted

Study results publicly available

February 25, 2025

Completed
Last Updated

February 25, 2025

Status Verified

February 1, 2025

Enrollment Period

1.4 years

First QC Date

November 30, 2020

Results QC Date

July 24, 2023

Last Update Submit

February 5, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • Composite Outcome of Symptomatic Deep Vein Thrombosis, Pulmonary Embolism, Other Venous Thromboembolism, Ischemic Stroke, Myocardial Infarction, Other Arterial Thromboembolism, and All-cause Mortality as Measured by Hospital Records.

    Composite endpoint (CE) of venous and arterial thrombotic complications-including new, symptomatic proximal, or distal DVT of the upper or lower extremities, PE, and new thrombosis of other veins (including cerebral sinus and splanchnic veins), ischemic stroke, myocardial infarction, other arterial thromboembolism (e.g., mesenteric or acute limb ischemia), and all-cause mortality by day 30.

    30 days after hospital discharge

Secondary Outcomes (6)

  • The Composite Outcome of All-cause Mortality and the EuroQoL Group 5-Dimension (EQ5D) Index Score.

    30 days after hospital discharge

  • The Composite Outcome of All-cause Mortality and the EQ5D Index Score.

    90 days after hospital discharge

  • The Composite Outcome of Symptomatic Deep Vein Thrombosis, Pulmonary Embolism, Other Venous Thromboembolism, Ischemic Stroke, Myocardial Infarction, Other Arterial Thromboembolism, and All-cause Mortality as Measured by Hospital Records.

    45 days after hospital discharge

  • The Composite Outcome of Symptomatic Deep Vein Thrombosis, Pulmonary Embolism, Other Venous Thromboembolism, Ischemic Stroke, Myocardial Infarction, Other Arterial Thromboembolism, and All-cause Mortality as Measured by Hospital Records.

    90 days after hospital discharge

  • New, Symptomatic VTE (Inclusive of DVT, PE, or Other Venous Thrombosis) for up to 30 Days After Randomization as Measured by Hospital Records.

    30 days after randomization (which occurred at time of hospital discharge)

  • +1 more secondary outcomes

Other Outcomes (3)

  • Percentage of Participants With All-cause Mortality

    30 days following discharge from hospital

  • The Incidence of All-cause Rehospitalization for up to 90 Days After Randomization

    90 days following discharge from hospital

  • The Individual Domains of EQ5D and the EQ5D Visual Analog Scale for 30 and 90 Days After Randomization

    30 and 90 days following discharge from hospital

Study Arms (2)

Apixaban

ACTIVE COMPARATOR

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.

Drug: Apixaban 2.5 MG

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

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.

Also known as: Eliquis
Apixaban

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.

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18 years
  • PCR-positive COVID-19 infection
  • Hospitalized for two or more days

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (121)

Valleywise Health Medical Center

Phoenix, Arizona, 85008, United States

Location

Dignity Health-St Josephs

Phoenix, Arizona, 85013, United States

Location

Central Arkansas Veterans Health Care System

Little Rock, Arkansas, 72205, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

UCSF at Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

Location

New Ananda Medical and Urgent Care, Inc.

South El Monte, California, 91733, United States

Location

Mazur and Statner MD PC

Thousand Oaks, California, 91360, United States

Location

Torrance Medical Center

Torrance, California, 90502, United States

Location

Centura Health Porter Adventist Hospital

Denver, Colorado, 80210, United States

Location

Saint Anthony Hospital

Lakewood, Colorado, 80228, United States

Location

St. Anthony North Health Campus

Westminster, Colorado, 80023, United States

Location

Baycare Hospital

Clearwater, Florida, 33756, United States

Location

Florida Heart Center

Ft. Pierce, Florida, 34590, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Tallahassee Memorial HealthCare

Tallahassee, Florida, 32308, United States

Location

James A. Haley Veteran's Hospital

Tampa, Florida, 33612, United States

Location

BayCare Hospital- Winter Haven

Winter Haven, Florida, 33881, United States

Location

Emory University

Atlanta, Georgia, 30308, United States

Location

Medical College of Georgia/Augusta University

Augusta, Georgia, 30912, United States

Location

Savannah Health Services, LLC DBA Memorial Health University Medical Center

Savannah, Georgia, 31404, United States

Location

Queens Medical Center

Honolulu, Hawaii, 96813, United States

Location

Hawaii Pacific Health

Honolulu, Hawaii, 96827, United States

Location

Snake River Research, PLLC

Idaho Falls, Idaho, 83404, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60607, United States

Location

Cook County Health

Chicago, Illinois, 60612, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

The University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

OSF Little Company of Mary

Evergreen Park, Illinois, 60805, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Indiana University Health Bloomington Hospital

Bloomington, Indiana, 47403, United States

Location

Lutheran Medical Group

Fort Wayne, Indiana, 46804, United States

Location

Indiana University Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Franciscan Health Michigan City

Michigan City, Indiana, 46360, United States

Location

Reid Physician Associates

Richmond, Indiana, 47374, United States

Location

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

Location

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

Location

Ochsner Clinic Foundation-Baton Rouge

New Orleans, Louisiana, 70121, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Willis-Knighton Physician Network/Tri-State Medical Clinic

Shreveport, Louisiana, 71103, United States

Location

Maine Medical Center/Maine Medical Partners Adult Hospital Medicine

Portland, Maine, 04102, United States

Location

Pen Bay Medical Center

Rockport, Maine, 04856, United States

Location

Anne Arundel Medical Center

Annapolis, Maryland, 21401, United States

Location

Lifebridge (Sinai Hospital of Baltimore)

Baltimore, Maryland, 21215, United States

Location

Adventist HealthCare Shady Grove Medical Center

Rockville, Maryland, 20850, United States

Location

Boston University

Boston, Massachusetts, 02118, United States

Location

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

Location

Baystate Medical center

Springfield, Massachusetts, 01199, United States

Location

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

Bay City, Michigan, 48708, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Western Michigan University

Kalamazoo, Michigan, 49008, United States

Location

MidMichigan Medical Center

Midland, Michigan, 48670, United States

Location

McLaren Macomb

Mount Clemens, Michigan, 48043, United States

Location

Minneapolis VA Health Care System

Minneapolis, Minnesota, 55417, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Truman Medical Center

Kansas City, Missouri, 64108, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

St Louis University

St Louis, Missouri, 63110, United States

Location

Mercury Street Medical Group

Butte, Montana, 59701, United States

Location

CHI St Elizabeth Hospital

Lincoln, Nebraska, 68510, United States

Location

Renown Health

Reno, Nevada, 89502, United States

Location

Dartmouth Hichcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

AtlantiCare Regional Medical Center

Atlantic City, New Jersey, 08401, United States

Location

Hope Tower at Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

Capital Health System, Inc.

Trenton, New Jersey, 08638, United States

Location

Christus St. Vincent Regional Medical Center

Santa Fe, New Mexico, 87505, United States

Location

NYU Langone Hospital-Brooklyn

Brooklyn, New York, 111220, United States

Location

Coney Island Hospital

Brooklyn, New York, 11235, United States

Location

Buffalo General Medical Center

Buffalo, New York, 14203, United States

Location

Mercy Hospital Buffalo

Buffalo, New York, 14220, United States

Location

Jamaica Hospital Medical Center

Jamaica, New York, 11418, United States

Location

New York University Langone Health

New York, New York, 10016, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Westchester Medical Center

Valhalla, New York, 10595, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Duke Medical Center

Durham, North Carolina, 27710, United States

Location

East Carolina University/Vidant Health

Greenville, North Carolina, 27858, United States

Location

Wake Med Hospital

Raleigh, North Carolina, 27610, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Summa Health

Akron, Ohio, 44304, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Kettering Medical Center

Kettering, Ohio, 45429, United States

Location

Ascension St. John Bartlesville

Tulsa, Oklahoma, 74104, United States

Location

Ascension St. John Tulsa

Tulsa, Oklahoma, 74104, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

St. Luke's University Health Network

Easton, Pennsylvania, 18045, United States

Location

Conemaugh Memorial Medical Center

Johnstown, Pennsylvania, 15905, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Tower Health Medical Group

West Reading, Pennsylvania, 19611, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

The Miriam Hospital

Providence, Rhode Island, 02906, United States

Location

Monument Health Clinical Research

Rapid City, South Dakota, 57701, United States

Location

Erlanger Health System

Chattanooga, Tennessee, 37403, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Christus St. Elizabeth Hospital

Beaumont, Texas, 77702, United States

Location

Baylor Scott and White Medical Center- College Station

College Station, Texas, 77845, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Texas Health Harris Methodist

Fort Worth, Texas, 76104, United States

Location

University of Texas- Houston, LBJ Hospital

Houston, Texas, 77030, United States

Location

UT Houston MHH-SW

Houston, Texas, 77030, United States

Location

UTHouston

Houston, Texas, 77030, United States

Location

Texas Health Frisco

Plano, Texas, 75024, United States

Location

Baylor Scott and White-Round Rock

Round Rock, Texas, 78665, United States

Location

Baylor Scott and White-Temple

Temple, Texas, 76508, United States

Location

The Woodlands Center For Respiratory & Sleep Research

The Woodlands, Texas, 77380, United States

Location

CHRISTUS Trinity Clinic Pulmonary Medicine

Tyler, Texas, 75701, United States

Location

The University of Texas Health Science Center at Tyler

Tyler, Texas, 75708, United States

Location

UT Health East Texas (Tyler)

Tyler, Texas, 75708, United States

Location

UT Rio Grande Valley

Weslaco, Texas, 78596, United States

Location

MultiCare Institute for Research & Innovation

Puyallup, Washington, 98372, United States

Location

UW Medicine Valley Medical Center

Renton, Washington, 98055, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

CAMC Clinical Trials Center

Charleston, West Virginia, 25304, United States

Location

West Virginia University Hospital

Morgantown, West Virginia, 26506, United States

Location

Blood Center of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

  • 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.

  • 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.

MeSH Terms

Conditions

COVID-19

Interventions

apixaban

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Results Point of Contact

Title
Dr. Thomas Ortel
Organization
Duke University Medical Center

Study Officials

  • Tracy Wang, MD

    Duke University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Double Blind
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

November 30, 2020

First Posted

December 2, 2020

Study Start

February 15, 2021

Primary Completion

July 24, 2022

Study Completion

September 23, 2022

Last Updated

February 25, 2025

Results First Posted

February 25, 2025

Record last verified: 2025-02

Data Sharing

IPD Sharing
Will not share

Locations