Purpose

This is a randomized, open label, adaptive platform trial to compare the effectiveness of antithrombotic strategies for prevention of adverse outcomes in COVID-19 positive inpatients

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • ≥ 18 years of age - Hospitalized for COVID-19 - Enrolled within 72 hours of hospital admittance or 72 hours of positive COVID test - Expected to require hospitalization for > 72 hours

Exclusion Criteria

  • Imminent death - Requirement for chronic mechanical ventilation via tracheostomy prior to hospitalization - Pregnancy - Based on a recommendation from the ACTIV4 DSMB on December 19, 2020, enrollment of patients requiring ICU level of care into the therapeutic anti-coagulation arm was stopped due to meeting a futility threshold and a potential for harm for this sub-group could not be excluded. Enrollment continues for moderately ill hospitalized COVID-19 patients.

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
This is an adaptive design
Primary Purpose
Treatment
Masking
None (Open Label)
Masking Description
There will be independent masked adjudicators.

Arm Groups

ArmDescriptionAssigned Intervention
Other
Therapeutic Dose Anticoagulation
increased dose of heparin above standard of care. This arm was stopped Jan 21, 2021
  • Drug: theraputic heparin
    increased dose of heparin above standard of care.
    Other names:
    • unfractionated heparin
    • Enoxaparin
    • Dalteparin
    • Tinzaparin
    • Heparin
Other
Prophylactic Dose Anticoagulation
Heparin standard of care This arm was stopped Jan 21, 2021
  • Drug: prophylactic heparin
    standard of care dose of heparin
    Other names:
    • enoxaparin
    • dalteparin
    • Tinzaparin
    • Fondparinux
    • Heparin
Other
Therapeutic Dose Anticoagulation + P2Y12 inhibitor
increased dose of heparin above standard of care with an added P2Y12 inhibitor
  • Drug: theraputic heparin
    increased dose of heparin above standard of care.
    Other names:
    • unfractionated heparin
    • Enoxaparin
    • Dalteparin
    • Tinzaparin
    • Heparin
  • Drug: P2Y12
    added P2Y12 inhibitor
    Other names:
    • Ticagrelor
    • Prasugrel
    • Clopidogrel
Other
Prophylactic Dose Anticoagulation + P2Y12 inhibitor
Heparin standard of care with an added P2Y12 inhibitor
  • Drug: prophylactic heparin
    standard of care dose of heparin
    Other names:
    • enoxaparin
    • dalteparin
    • Tinzaparin
    • Fondparinux
    • Heparin
  • Drug: P2Y12
    added P2Y12 inhibitor
    Other names:
    • Ticagrelor
    • Prasugrel
    • Clopidogrel

Recruiting Locations

University of Alabama
Birmingham, Alabama 35233
Contact:
Shetal Gandotra

Ronald Reagan UCLA Medical Center
Los Angeles, California 90095
Contact:
George Lim

UC San Diego Hillcrest
San Diego, California 92103
Contact:
Todd Constantini

Zuckerberg San Francisco General Hospital
San Francisco, California 94110
Contact:
Lucy Kornblith

UCSF San Francisco
San Francisco, California 94143
Contact:
Michael Matthay

Stanford University Medical Center
Stanford, California 94305
Contact:
Jennifer Wilson

Denver Health and Hospital Authority
Denver, Colorado 80401
Contact:
Mitchell Cohen

Saint Francis Hospital and Medical Center
Hartford, Connecticut 06105
Contact:
Sudhanshu Mulay

University of Florida
Gainesville, Florida 32608
Contact:
Marie-Carmelle Elie

Cook County Health
Chicago, Illinois 60612
Contact:
Saurabh Malhotra

University of Illinois at Chicago Health (UIH)
Chicago, Illinois 60612
Contact:
John Quigley

Kansas University Medical Center
Kansas City, Kansas 66160
Contact:
Lewis Satterwhite

Boston University
Boston, Massachusetts 02118
Contact:
Naomi Hamburg

Baystate Medical Center
Springfield, Massachusetts 01199
Contact:
Mark Tidswell

University of Michigan
Ann Arbor, Michigan 48109
Contact:
Robert Hyzy

Wayne State University
Detroit, Michigan 48201
Contact:
Robert Sherwin

Hennepin County Medical Center
Minneapolis, Minnesota 55415
Contact:
Matt Prekker

University of Mississippi Medical Center
Jackson, Mississippi 39216
Contact:
Matthew Kutcher

Washington University School of Medicine, ACCS Research
Saint Louis, Missouri 63110
Contact:
Grant Bochicchio

Rutgers New Jersey Medical School
Newark, New Jersey 07103
Contact:
Yonatan Greenstein

Albany Medical College
Albany, New York 12208
Contact:
Mandeep Sidhu

Jacobi Medical Center
Bronx, New York 10461
Contact:
Eleonora Gashi

Montefiore Medical Center
Bronx, New York 10461
Contact:
Michelle Gong

VA New York Harbor Healthcare System
New York, New York 10010
Contact:
Binita Shah

NYU Langone
New York, New York 10016
Contact:
Jeffrey Berger, MD
212-263-0855
Jeffrey.Berger@nyulangone.org

Duke University Hospital
Durham, North Carolina 27704
Contact:
Lana Wahid

University of Cincinnati Medical Center
Cincinnati, Ohio 45219
Contact:
Kristin Hudock

The MetroHealth System
Cleveland, Ohio 44109
Contact:
Vidya Krishnan

Cleveland Clinic Foundation
Cleveland, Ohio 44195
Contact:
Abhijit Duggal

Ascension St. John Clinical Research Institute
Tulsa, Oklahoma 74104
Contact:
Nicholas Hanna

Oregon Health and Science University
Portland, Oregon 97239
Contact:
Akram Kahn

Penn State Health Milton S. Hershey Medical Center
Hershey, Pennsylvania 17033
Contact:
Steven Moore

Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania 19104
Contact:
Allyson Pishko

UPMC Presbyterian
Pittsburgh, Pennsylvania 15260
Contact:
David Huang

Sarah Cannon and HCA Research Institute
Nashville, Tennessee 37203
Contact:
Andrew Goodman

University of Texas Southwestern Medical Center
Dallas, Texas 75390
Contact:
Ambarish Pandey

Baylor Scott and White Medical Center - Temple
Temple, Texas 76508
Contact:
Robert Widmer

Swedish Hospital
Seattle, Washington 98122
Contact:
David Wilson

University of Wisconsin Hospital; Meriter Hospital (UW affiliated)
Madison, Wisconsin 53715
Contact:
John Sheehan

More Details

NCT ID
NCT04505774
Status
Recruiting
Sponsor
Matthew Neal MD

Study Contact

Judith Hochman, MD
212-263-6927
Judith.Hochman@nyulangone.org

Detailed Description

The severe acute respiratory syndrome coronavirus 2, which causes the highly contagious coronavirus disease 2019 (COVID-19), has resulted in a global pandemic. The clinical spectrum of COVID-19 infection is broad, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia with respiratory failure and death. The risk of thrombotic complications is increased, even as compared to other viral respiratory illnesses, such as influenza. A pro-inflammatory cytokine response as well as induction of procoagulant factors associated with COVID-19 has been proposed to contribute to thrombosis as well as plaque rupture through local inflammation. Patients with COVID-19 are at increased risk for arterial and vein thromboembolism, with high rates observed despite thromboprophylaxis. Autopsy reports have noted micro and macro vascular thrombosis across multiple organ beds consistent with an early hypercoagulable state. Notably, in COVID-19, data in the U.K. and U.S. document that infection and outcomes of infection are worse in African and Hispanic descent persons than in other groups. The reasons for this are uncertain. Viral Infection and Thrombosis A large body of literature links inflammation and coagulation; altered hemostasis is a known complication of respiratory viral infections. Procoagulant markers are severely elevated in viral infections. Specifically, proinflammatory cytokines in viral infections upregulate expression of tissue factor, markers of thrombin generation, platelet activation, and down-regulate natural anticoagulant proteins C and S. Studies have demonstrated significant risk of deep venous thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction (MI) associated with viral respiratory infections. In a series of patients with fatal influenza H1N1, 75% had pulmonary thrombi on autopsy (a rate considerably higher than reported on autopsy studies among the general intensive care unit population). Incidence ratio for acute myocardial infarction in the context of Influenza A is over 10. Severe acute respiratory syndrome coronavirus-1 (SARS CoV-1) and influenza have been associated with disseminated intravascular coagulation (DIC), endothelial damage, DVT, PE, and large artery ischemic stroke. Patients with Influenza H1N1 and acute respiratory distress syndrome (ARDS) had a 23.3-fold higher risk for pulmonary embolism, and a 17.9-fold increased risk for deep vein thrombosis. Compared to those treated with systemic anticoagulation, those without treatment were 33 times more likely to suffer a VTE. Thrombosis, both microvascular and macrovascular, is a prominent feature in multiple organs at autopsy in fatal cases of COVID-19. Thrombosis may thus contribute to respiratory failure, renal failure, and hepatic injury in COVID-19. The number of megakaryocytes in tissues is higher than in other forms of ARDS, and thrombi are platelet-rich based on specific staining. Thrombotic stroke has been reported in young COVID-19 patients with no cardiovascular risk factors. Both arterial and venous thrombotic events have been seen in increasing numbers of hospitalized patients infected with COVID-19. The incidence of thrombosis has ranged from 10 to 30% in hospitalized patients; however, this varies by type of thrombosis captured (arterial or vein) and severity of illness (ICU level care, requiring mechanical ventilation, etc.).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.