COVID-19 Thrombosis Prevention Trials: Post-hospital Thromboprophylaxis

COVID-19 Post-hospital Thrombosis Prevention Trial: An Adaptive, Multicenter, Prospective, Randomized Platform Trial Evaluating the Efficacy and Safety of Antithrombotic Strategies in Patients With COVID-19 Following Hospital Discharge

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

Study Overview

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

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 1291
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85008
      • Valleywise Health Medical Center
    • Phoenix, Arizona, United States, 85013
      • Dignity Health-St Josephs
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
    • Little Rock, Arkansas, United States, 72205
      • Central Arkansas Veterans Health Care System
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University School of Medicine
    • S. El Monte, California, United States, 91733
      • New Ananda Medical and Urgent Care, Inc.
    • San Francisco, California, United States, 94110
      • UCSF at Zuckerberg San Francisco General Hospital
    • Thousand Oaks, California, United States, 91360
      • Mazur and Statner MD PC
    • Torrance, California, United States, 90502
      • Torrance Medical Center
  • Colorado
    • Denver, Colorado, United States, 80210
      • Centura Health Porter Adventist Hospital
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Westminster, Colorado, United States, 80023
      • St. Anthony North Health Campus
  • Florida
    • Clearwater, Florida, United States, 33756
      • Baycare Hospital
    • Fort Pierce, Florida, United States, 34590
      • Florida Heart Center
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial HealthCare
    • Tampa, Florida, United States, 33612
      • James A. Haley Veteran's Hospital
    • Winter Haven, Florida, United States, 33881
      • BayCare Hospital- Winter Haven
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia/Augusta University
    • Savannah, Georgia, United States, 31404
      • Savannah Health Services, LLC DBA Memorial Health University Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queens Medical Center
    • Honolulu, Hawaii, United States, 96827
      • Hawaii Pacific Health
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Snake River Research, PLLC
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60612
      • Cook County Health
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medicine
    • Chicago, Illinois, United States, 60607
      • University of Illinois at Chicago
    • Evergreen Park, Illinois, United States, 60805
      • OSF Little Company of Mary
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • Bloomington, Indiana, United States, 47403
      • Indiana University Health Bloomington Hospital
    • Fort Wayne, Indiana, United States, 46804
      • Lutheran Medical Group
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Methodist Hospital
    • Michigan City, Indiana, United States, 46360
      • Franciscan Health Michigan City
    • Richmond, Indiana, United States, 47374
      • Reid Physician Associates
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation-Baton Rouge
    • Shreveport, Louisiana, United States, 71103
      • Willis-Knighton Physician Network/Tri-State Medical Clinic
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center/Maine Medical Partners Adult Hospital Medicine
    • Rockport, Maine, United States, 04856
      • Pen Bay Medical Center
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Medical Center
    • Baltimore, Maryland, United States, 21215
      • Lifebridge (Sinai Hospital of Baltimore)
    • Rockville, Maryland, United States, 20850
      • Adventist HealthCare Shady Grove Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Michigan
    • Bay City, Michigan, United States, 48708
      • Bay Regional Medical Center d/b/a/ McLaren Bay Region
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Kalamazoo, Michigan, United States, 49008
      • Western Michigan University
    • Midland, Michigan, United States, 48670
      • MidMichigan Medical Center
    • Mount Clemens, Michigan, United States, 48043
      • McLaren Macomb
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Health Care System
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Truman Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
    • Saint Louis, Missouri, United States, 63110
      • St Louis University
  • Montana
    • Butte, Montana, United States, 59701
      • Mercury Street Medical Group
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • CHI St Elizabeth Hospital
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Health
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hichcock Medical Center
  • New Jersey
    • Atlantic City, New Jersey, United States, 08401
      • AtlantiCare Regional Medical Center
    • Neptune, New Jersey, United States, 07753
      • HOPE Tower at Jersey Shore University Medical Center
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
    • Trenton, New Jersey, United States, 08638
      • Capital Health System, Inc.
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Christus St. Vincent Regional Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Brooklyn, New York, United States, 11235
      • Coney Island Hospital
    • Brooklyn, New York, United States, 111220
      • NYU Langone Hospital-Brooklyn
    • Buffalo, New York, United States, 14203
      • Buffalo General Medical Center
    • Buffalo, New York, United States, 14220
      • Mercy Hospital Buffalo
    • Jamaica, New York, United States, 11418
      • Jamaica Hospital Medical Center
    • New York, New York, United States, 10016
      • New York University Langone Health
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Hospital
    • Valhalla, New York, United States, 10595
      • Westchester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke Medical Center
    • Greenville, North Carolina, United States, 27858
      • East Carolina University/Vidant Health
    • Raleigh, North Carolina, United States, 27610
      • Wake Med Hospital
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Ohio State University
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Ascension St. John Bartlesville
    • Tulsa, Oklahoma, United States, 74104
      • Ascension St. John Tulsa
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Easton, Pennsylvania, United States, 18045
      • St. Luke's University Health Network
    • Johnstown, Pennsylvania, United States, 15905
      • Conemaugh Memorial Medical Center
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
    • West Reading, Pennsylvania, United States, 19611
      • Tower Health Medical Group
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Monument Health Clinical Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Health System
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Beaumont, Texas, United States, 77702
      • Christus St. Elizabeth Hospital
    • College Station, Texas, United States, 77845
      • Baylor Scott and White Medical Center- College Station
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Fort Worth, Texas, United States, 76104
      • Texas Health Harris Methodist
    • Houston, Texas, United States, 77030
      • University of Texas- Houston, LBJ Hospital
    • Houston, Texas, United States, 77030
      • UT Houston MHH-SW
    • Houston, Texas, United States, 77030
      • UTHouston
    • Plano, Texas, United States, 75024
      • Texas Health Frisco
    • Round Rock, Texas, United States, 78665
      • Baylor Scott and White-Round Rock
    • Temple, Texas, United States, 76508
      • Baylor Scott and White-Temple
    • The Woodlands, Texas, United States, 77380
      • The Woodlands Center For Respiratory & Sleep Research
    • Tyler, Texas, United States, 75708
      • The University of Texas Health Science Center at Tyler
    • Tyler, Texas, United States, 75701
      • CHRISTUS Trinity Clinic Pulmonary Medicine
    • Tyler, Texas, United States, 75708
      • UT Health East Texas (Tyler)
    • Weslaco, Texas, United States, 78596
      • UT Rio Grande Valley
  • Washington
    • Puyallup, Washington, United States, 98372
      • MultiCare Institute for Research & Innovation
    • Renton, Washington, United States, 98055
      • UW Medicine Valley Medical Center
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • CAMC Clinical Trials Center
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Blood Center of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

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

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
Active Comparator: 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.	Drug: 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.; Other Names: Eliquis
Placebo Comparator: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Composite Outcome of All-cause Mortality and the EuroQoL Group 5-Dimension (EQ5D) Index Score.	Composite endpoint of mortality and EQ5D index at Day 30. All mortality events will be considered worse than any possible EQ5D response [QOL&M30]. Death was designated as a score of 0. Scores range from 0 (where 0 is the value of a health state equivalent to dead) to 1 (the value of full health), with higher scores indicating higher health utility.	30 days after hospital discharge
The Composite Outcome of All-cause Mortality and the EQ5D Index Score.	Composite endpoint of mortality and EQ5D index at Day 90. All mortality events will be considered worse than any possible EQ5D response. Death was designated as a score of 0. Scores range from 0 (where 0 is the value of a health state equivalent to dead) to 1 (the value of full health), with higher scores indicating higher health utility.	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)
New, Symptomatic ATE (Inclusive of Ischemic Stroke, MI, or Peripheral Arterial Thromboembolism) for up to 30 Days After Randomization as Measured by Hospital Records.		30 days after randomization (which occurred at time of hospital discharge)

Other Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Thomas L. Ortel
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Tracy Wang, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2021
• Primary Completion (Actual): July 24, 2022
• Study Completion (Actual): September 23, 2022

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (Actual): December 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Thrombosis; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Apixaban
• Other Study ID Numbers: Pro00107078

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No