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Anticoagulation in Critically Ill Patients With COVID-19 (The IMPACT Trial) (IMPACT)

Primary Purpose

COVID-19

Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Enoxaparin sodium
Unfractionated heparin
Fondapariniux
Argatroban
Sponsored by
Weill Medical College of Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring COVID-19, Anticoagulation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age >18 years old
  • COVID-19 positive on (RT-PCR) nasopharyngeal swab, or suspected COVID-19 infection with detectable SARS-CoV-2 IgG or IgM.
  • Intensive care unit (ICU) patient or non-ICU patient on invasive mechanical ventilation, BiPAP, 100% non-rebreather mask, or high flow oxygen or supplemental oxygen of at least 4 liters per minute nasal cannula.
  • D dimer level greater than 700 ng/mL (3 times the upper limit of normal).

Exclusion Criteria:

  • Objectively documented deep vein thrombosis or pulmonary embolism
  • Patients in whom there is very high suspicion for pulmonary embolism and are on full-dose anticoagulation as per the treating physician
  • Platelets <30,000 not due to disseminated intravascular coagulation (DIC), based on the International Society of Thrombosis and Haemostasis (ISTH) criteria and American Society of Hematology (ASH) Frequently Asked Questions
  • Active bleeding that poses a contraindication to therapeutic anticoagulation in the opinion of the investigator.
  • History of bleeding diathesis (e.g., hemophilia, severe von Willebrand disease, severe thrombocytopathy)
  • History of intracranial hemorrhage in the last 90 days
  • History of ischemic stroke in the past 2 weeks
  • Major neurosurgical procedure in the past 30 days
  • Cardiothoracic surgery in the past 30 days
  • Intra-abdominal surgery in the past 30 days
  • Intracranial malignancy
  • Patients who require therapeutic anticoagulation for other reasons like atrial fibrillation, deep venous thrombosis, pulmonary embolism, or antiphospholipid syndrome.

Sites / Locations

  • New York Presbyterian Brooklyn Methodist Hospital
  • Weill Cornell Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Intermediate Dose Prophylaxis

Therapeutic Dose Anticoagulation

Arm Description

Subjects will receive one of the following interventions, at their physician's discretion: Enoxaparin 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min Enoxaparin 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 mL/min If patient develops acute kidney injury: unfractionated heparin 7,500 units subcutaneously every 8 hours. Fondaparinux (if history of heparin-inducted thrombocytopenia [HIT]) 2.5 mg daily subcutaneously

Subjects will receive one of the following interventions, at their physician's discretion: Unfractionated heparin (UFH) to target anti-Xa level 0.3 -0.7 IU/mL or activated partial thromboplastin time (aPTT) (according to institutional protocol). Enoxaparin 1 mg/kg subcutaneously every 12 hours Argatroban (if heparin-induced thrombocytopenia [HIT]), dosed according to institutional protocol. Fondaparinux (if HIT and creatinine clearance greater than or equal to 50 ml/min) dosed by weight: ≥100 kg: 10 mg daily <100 kg but ≥50 kg: 7.5 mg daily <50 kg: 5 mg daily

Outcomes

Primary Outcome Measures

30-day Mortality
Comparison of number of COVID-19 positive patients who have died within 30 days of starting treatment on each treatment arm

Secondary Outcome Measures

Length of Intensive Care Unit (ICU) Stay in Days
Comparison of length of ICU stay in days between each treatment arm.
Number of Documented Venous Thromboembolism (VTE), Arterial Thrombosis (Stroke, Myocardial Infarction, Other) and Microthrombosis Events
Comparison of number of documented VTE, arterial thrombosis and microthrombosis events on each treatment arm
Number of Major and Clinically Relevant Non-major Bleeding Events
Comparison of major and clinically-relevant non-major bleeding events on each treatment arm, as defined by the International Society of Thrombosis and Haemostasis (ISTH) criteria.

Full Information

First Posted
May 26, 2020
Last Updated
August 24, 2023
Sponsor
Weill Medical College of Cornell University
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1. Study Identification

Unique Protocol Identification Number
NCT04406389
Brief Title
Anticoagulation in Critically Ill Patients With COVID-19 (The IMPACT Trial)
Acronym
IMPACT
Official Title
InterMediate ProphylACtic Versus Therapeutic Dose Anticoagulation in Critically Ill Patients With COVID-19: A Prospective Randomized Study (The IMPACT Trial)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
Low accrual
Study Start Date
October 13, 2020 (Actual)
Primary Completion Date
April 17, 2021 (Actual)
Study Completion Date
April 21, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine if therapeutic dose anticoagulation (experimental group) improves 30-day mortality in participants with COVID-19 compared to those patients receiving the intermediate dose prophylaxis (control group). Following screening, subjects will be randomized 1:1 to intermediate dose prophylaxis or therapeutic dose anticoagulation treatment arms.Treatment will continue for 28 days, followed by a 6 month follow-up period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
COVID-19, Anticoagulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intermediate Dose Prophylaxis
Arm Type
Active Comparator
Arm Description
Subjects will receive one of the following interventions, at their physician's discretion: Enoxaparin 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min Enoxaparin 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 mL/min If patient develops acute kidney injury: unfractionated heparin 7,500 units subcutaneously every 8 hours. Fondaparinux (if history of heparin-inducted thrombocytopenia [HIT]) 2.5 mg daily subcutaneously
Arm Title
Therapeutic Dose Anticoagulation
Arm Type
Experimental
Arm Description
Subjects will receive one of the following interventions, at their physician's discretion: Unfractionated heparin (UFH) to target anti-Xa level 0.3 -0.7 IU/mL or activated partial thromboplastin time (aPTT) (according to institutional protocol). Enoxaparin 1 mg/kg subcutaneously every 12 hours Argatroban (if heparin-induced thrombocytopenia [HIT]), dosed according to institutional protocol. Fondaparinux (if HIT and creatinine clearance greater than or equal to 50 ml/min) dosed by weight: ≥100 kg: 10 mg daily <100 kg but ≥50 kg: 7.5 mg daily <50 kg: 5 mg daily
Intervention Type
Drug
Intervention Name(s)
Enoxaparin sodium
Other Intervention Name(s)
Lovenox
Intervention Description
Intermediate Dose Prophylaxis Arm: 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min --OR-- 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min Therapeutic Dose Anticoagulation Arm: 1 mg/kg subcutaneously every 12 hours
Intervention Type
Drug
Intervention Name(s)
Unfractionated heparin
Other Intervention Name(s)
Sodium heparin
Intervention Description
Intermediate Dose Prophylaxis Arm: 7,500 units subcutaneously every 8 hours Therapeutic Dose Anticoagulation Arm: Dosed to target anti-Xa level 0.3 - 0.7 IU/mL or activated partial thromboplastin time (aPTT), according to institutional protocol
Intervention Type
Drug
Intervention Name(s)
Fondapariniux
Other Intervention Name(s)
Arixtra
Intervention Description
Intermediate Dose Prophylaxis Arm: 2.5 mg daily subcutaneously Therapeutic Dose Anticoagulation Arm: Dose by weight: If greater than or equal to 100 kg: 10 mg daily If less than 100 kg but greater than or equal to 50 kg: 7.5 mg daily If less than 50 kg: 5 mg daily
Intervention Type
Drug
Intervention Name(s)
Argatroban
Intervention Description
Therapeutic Dose Anticoagulation Arm: Dosed according to institutional protocol
Primary Outcome Measure Information:
Title
30-day Mortality
Description
Comparison of number of COVID-19 positive patients who have died within 30 days of starting treatment on each treatment arm
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Length of Intensive Care Unit (ICU) Stay in Days
Description
Comparison of length of ICU stay in days between each treatment arm.
Time Frame
6 months
Title
Number of Documented Venous Thromboembolism (VTE), Arterial Thrombosis (Stroke, Myocardial Infarction, Other) and Microthrombosis Events
Description
Comparison of number of documented VTE, arterial thrombosis and microthrombosis events on each treatment arm
Time Frame
6 months
Title
Number of Major and Clinically Relevant Non-major Bleeding Events
Description
Comparison of major and clinically-relevant non-major bleeding events on each treatment arm, as defined by the International Society of Thrombosis and Haemostasis (ISTH) criteria.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age >18 years old COVID-19 positive on (RT-PCR) nasopharyngeal swab, or suspected COVID-19 infection with detectable SARS-CoV-2 IgG or IgM. Intensive care unit (ICU) patient or non-ICU patient on invasive mechanical ventilation, BiPAP, 100% non-rebreather mask, or high flow oxygen or supplemental oxygen of at least 4 liters per minute nasal cannula. D dimer level greater than 700 ng/mL (3 times the upper limit of normal). Exclusion Criteria: Objectively documented deep vein thrombosis or pulmonary embolism Patients in whom there is very high suspicion for pulmonary embolism and are on full-dose anticoagulation as per the treating physician Platelets <30,000 not due to disseminated intravascular coagulation (DIC), based on the International Society of Thrombosis and Haemostasis (ISTH) criteria and American Society of Hematology (ASH) Frequently Asked Questions Active bleeding that poses a contraindication to therapeutic anticoagulation in the opinion of the investigator. History of bleeding diathesis (e.g., hemophilia, severe von Willebrand disease, severe thrombocytopathy) History of intracranial hemorrhage in the last 90 days History of ischemic stroke in the past 2 weeks Major neurosurgical procedure in the past 30 days Cardiothoracic surgery in the past 30 days Intra-abdominal surgery in the past 30 days Intracranial malignancy Patients who require therapeutic anticoagulation for other reasons like atrial fibrillation, deep venous thrombosis, pulmonary embolism, or antiphospholipid syndrome.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maria T DeSancho, MD, MSc
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York Presbyterian Brooklyn Methodist Hospital
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11215
Country
United States
Facility Name
Weill Cornell Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
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Anticoagulation in Critically Ill Patients With COVID-19 (The IMPACT Trial)

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