Hamburg Edoxaban for Anticoagulation in COVID-19 Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Hamburg Edoxaban for Anticoagulation in COVID-19 Study

Conditions
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Covid19

Intervention / Treatment
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* Drug: Anticoagulation Agents (Edoxaban and/or high dose LMWH)
* Drug: Low dose Low molecular weight heparin or Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive anticoagulation strategy<br>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 | Drug: Anticoagulation Agents (Edoxaban and/or high dose LMWH)<br>* 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<br>|
| Other: Moderate anticoagulation strategy<br>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 | Drug: Low dose Low molecular weight heparin or Placebo<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | All-cause mortality during follow-up (42 days) | 42 days | 
| Mortality related to venous thromboembolism | Mortality related to venous thromboembolism during follow-up (42 days) | 42 days | 
| Mortality related to arterial thromboembolism | Mortality related to arterial thromboembolism during follow-up (42 days) | 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 | 42 days | 
| Rate and length of mechanical ventilation | Rate and length of mechanical Ventilation during follow-up (42 days) | 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) | 42 days | 
| Rehospitalisation | Rehospitalisation during follow-up (42 days) | 42 days | 
| Rate and length of renal replacement therapy | Rate and length of renal replacement therapy during follow-up (42 days) | 42 days | 
| Cardiac arrest/ CPR | Cardiac arrest/ CPR during follow-up (42 days) | 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coagulopathy