Hamburg Edoxaban for Anticoagulation in COVID-19 Study (HERO-19)
Primary Purpose
Covid19
Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Anticoagulation Agents (Edoxaban and/or high dose LMWH)
Low dose Low molecular weight heparin or Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Covid19 focused on measuring Coagulopathy
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of COVID-19 and hospitalization on ICU, or
- Diagnosis of COVID-19 and hospitalization on normal ward, or
- Diagnosis of COVID-19 (within 10 days) and troponin ≥ ULN and/or D-dimer ≥0.5 mg/L
Exclusion Criteria:
- Age below 18
- Life expectancy less than 3 months before COVID-19
- Resuscitation > 30 minutes
- Hypersensitivity to the active substance, to Edoxaban or any of its excipients
- Significantly increased bleeding risk
- Other indication for anticoagulation beyond COVID-19
- GFR < 15 ml/min
- Planned transfer of the patient to another clinic within the next 42 days
Sites / Locations
- UK Aachen
- Universitätsklinikum Augsburg
- Universitätsklinikum Düsseldorf
- Universitätsklinikum Freiburg
- Asklepios Klinik Altona
- Asklepios Klinik Barmbek
- Asklepios Klinik St. Georg
- Universitärsklinikum Hamburg-Eppendorf
- Medizinische Hochschule Hannover
- TU München Klinikum rechts der Isar
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Intensive anticoagulation strategy
Moderate anticoagulation strategy
Arm Description
In-hospital (ICU & normal ward): weight-adapted LMWH, high dose/ therapeutic dose (according to respective SmPC) After discharge and in ambulatory patients: Edoxaban according to SmPC
In-hospital (ICU & normal ward): LMWH, prophylactic dose as part of SOC After discharge and in ambulatory patients: Administration of oral placebo according to the dosing rules for Edoxaban
Outcomes
Primary Outcome Measures
Combined endpoint: all-cause mortality and/ or venous thromboem-bolism and/ or arterial thromboembolism
All-cause mortality and/ or venous thromboem-bolism and/ or arterial thromboembolism during follow-up (42 days). Thromboembolisms will be detected by duplex ultrasonography of arms and legs.
Secondary Outcome Measures
All-cause mortality
All-cause mortality during follow-up (42 days)
Mortality related to venous thromboembolism
Mortality related to venous thromboembolism during follow-up (42 days)
Mortality related to arterial thromboembolism
Mortality related to arterial thromboembolism during follow-up (42 days)
Rate of venous and/ or arterial thromboembolism
Rate of venous and/ or arterial thromboembolism during follow-up (42 days) Thromboembolisms will be detected by duplex ultrasonography of arms and legs
Rate and length of mechanical ventilation
Rate and length of mechanical Ventilation during follow-up (42 days)
Length of initial stay at ICU after application of IMP
Length of initial stay at ICU after application of IMP during follow-up (42 days)
Rehospitalisation
Rehospitalisation during follow-up (42 days)
Rate and length of renal replacement therapy
Rate and length of renal replacement therapy during follow-up (42 days)
Cardiac arrest/ CPR
Cardiac arrest/ CPR during follow-up (42 days)
Full Information
NCT ID
NCT04542408
First Posted
September 6, 2020
Last Updated
May 21, 2023
Sponsor
Universitätsklinikum Hamburg-Eppendorf
1. Study Identification
Unique Protocol Identification Number
NCT04542408
Brief Title
Hamburg Edoxaban for Anticoagulation in COVID-19 Study
Acronym
HERO-19
Official Title
Hamburg Edoxaban for Anticoagulation in COVID-19 Study
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
November 12, 2020 (Actual)
Primary Completion Date
September 6, 2022 (Actual)
Study Completion Date
January 15, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitätsklinikum Hamburg-Eppendorf
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Hero-19 aims to evaluate if an intensive anticoagulation strategy using Edoxaban on top of standard of care (SOC) of COVID-19 therapy is superior to SOC (in-hospital moderate anticoagulation strategy = low-dose low-molecular weight heparin [LMWH], ambulatory no anticoagulation, i.e. placebo within this trial) in reduction of morbidity and mortality endpoints in patients with COVID-19.
Detailed Description
Coagulopathy in the context of COVID-19 is a major threat to affected patients due to deep vein thromboses and pulmonary embolisms. Actual data show an unexpectedly high incidence of partially fatal complications without any prior clinical evidence in some cases. Therefore, this prospective, randomized, assessor-blinded, multicenter, placebo-controlled, interventional trial will investigate whether therapeutic anticoagulation on top of SOC compared to prophylactic anticoagulation as part of SOC- can improve objective patient-relative endpoints, relevant for prognosis in patients with COVID-19. 172 eligible patients will be randomized 1:1 to experimental or control group. Patients enrolled to experimental group will receive therapeutic anticoagulation using LMWH body weight-adapted during course of hospital stay and oral anticoagulation using Edoxaban according to SmPC (60mg once a day) after being discharged from hospital / outpatient course. Patients enrolled to control group will receive prophylactic anticoagulation using LMWH as part of SOC whilst inpatient course, and placebo after discharge / outpatient course. Patients will be informed of their allocation to the placebo group, as it has been shown that the effect of placebo is still detectable.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
Keywords
Coagulopathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
140 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intensive anticoagulation strategy
Arm Type
Experimental
Arm Description
In-hospital (ICU & normal ward): weight-adapted LMWH, high dose/ therapeutic dose (according to respective SmPC) After discharge and in ambulatory patients: Edoxaban according to SmPC
Arm Title
Moderate anticoagulation strategy
Arm Type
Other
Arm Description
In-hospital (ICU & normal ward): LMWH, prophylactic dose as part of SOC After discharge and in ambulatory patients: Administration of oral placebo according to the dosing rules for Edoxaban
Intervention Type
Drug
Intervention Name(s)
Anticoagulation Agents (Edoxaban and/or high dose LMWH)
Intervention Description
In-hospital (ICU & normal ward): weight-adapted LMWH, high dose/ therapeutic dose (according to respective SmPC) After discharge and in ambulatory patients: Edoxaban according to SmPC until
Intervention Type
Drug
Intervention Name(s)
Low dose Low molecular weight heparin or Placebo
Intervention Description
In-hospital (ICU & normal ward): LMWH, prophylactic dose as part of SOC After discharge and in ambulatory patients: Administration of oral pla-cebo according to the dosing rules for Edoxaban
Primary Outcome Measure Information:
Title
Combined endpoint: all-cause mortality and/ or venous thromboem-bolism and/ or arterial thromboembolism
Description
All-cause mortality and/ or venous thromboem-bolism and/ or arterial thromboembolism during follow-up (42 days). Thromboembolisms will be detected by duplex ultrasonography of arms and legs.
Time Frame
42 days
Secondary Outcome Measure Information:
Title
All-cause mortality
Description
All-cause mortality during follow-up (42 days)
Time Frame
42 days
Title
Mortality related to venous thromboembolism
Description
Mortality related to venous thromboembolism during follow-up (42 days)
Time Frame
42 days
Title
Mortality related to arterial thromboembolism
Description
Mortality related to arterial thromboembolism during follow-up (42 days)
Time Frame
42 days
Title
Rate of venous and/ or arterial thromboembolism
Description
Rate of venous and/ or arterial thromboembolism during follow-up (42 days) Thromboembolisms will be detected by duplex ultrasonography of arms and legs
Time Frame
42 days
Title
Rate and length of mechanical ventilation
Description
Rate and length of mechanical Ventilation during follow-up (42 days)
Time Frame
42 days
Title
Length of initial stay at ICU after application of IMP
Description
Length of initial stay at ICU after application of IMP during follow-up (42 days)
Time Frame
42 days
Title
Rehospitalisation
Description
Rehospitalisation during follow-up (42 days)
Time Frame
42 days
Title
Rate and length of renal replacement therapy
Description
Rate and length of renal replacement therapy during follow-up (42 days)
Time Frame
42 days
Title
Cardiac arrest/ CPR
Description
Cardiac arrest/ CPR during follow-up (42 days)
Time Frame
42 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of COVID-19 and hospitalization on ICU, or
Diagnosis of COVID-19 and hospitalization on normal ward, or
Diagnosis of COVID-19 (within 10 days) and troponin ≥ ULN and/or D-dimer ≥0.5 mg/L
Exclusion Criteria:
Age below 18
Life expectancy less than 3 months before COVID-19
Resuscitation > 30 minutes
Hypersensitivity to the active substance, to Edoxaban or any of its excipients
Significantly increased bleeding risk
Other indication for anticoagulation beyond COVID-19
GFR < 15 ml/min
Planned transfer of the patient to another clinic within the next 42 days
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stefan Kluge, MD
Organizational Affiliation
Universitätsklinikum Hamburg-Eppendorf
Official's Role
Principal Investigator
Facility Information:
Facility Name
UK Aachen
City
Aachen
Country
Germany
Facility Name
Universitätsklinikum Augsburg
City
Augsburg
Country
Germany
Facility Name
Universitätsklinikum Düsseldorf
City
Düsseldorf
Country
Germany
Facility Name
Universitätsklinikum Freiburg
City
Freiburg
Country
Germany
Facility Name
Asklepios Klinik Altona
City
Hamburg
Country
Germany
Facility Name
Asklepios Klinik Barmbek
City
Hamburg
Country
Germany
Facility Name
Asklepios Klinik St. Georg
City
Hamburg
Country
Germany
Facility Name
Universitärsklinikum Hamburg-Eppendorf
City
Hamburg
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hanover
Country
Germany
Facility Name
TU München Klinikum rechts der Isar
City
München
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Hamburg Edoxaban for Anticoagulation in COVID-19 Study
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