Hamburg Edoxaban for Anticoagulation in COVID-19 Study

Phase 3

Completed

• Conditions: Covid19
• Interventions: Drug: Anticoagulation Agents (Edoxaban and/or high dose LMWH); Drug: Low dose Low molecular weight heparin or Placebo

• Registration Number: NCT04542408
• Lead Sponsor: Universitätsklinikum Hamburg-Eppendorf

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.

Study Timeline

• Study First Submitted: 2020-09-06
• Study First Submitted QC: 2020-09-06
• Study First Posted: 2020-09-09
• Study Start: 2020-11-12
• Primary Completion: 2022-09-06
• Study Completion: 2023-01-15
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-21
• Last Update Posted: 2023-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 140

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intensive anticoagulation strategy	Anticoagulation Agents (Edoxaban and/or high dose LMWH)	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
Moderate anticoagulation strategy	Low dose Low molecular weight heparin or Placebo	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

Primary Outcome Measures

Name	Time	Method
Combined endpoint: all-cause mortality and/ or venous thromboem-bolism and/ or arterial thromboembolism	42 days	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

Name	Time	Method
Rate and length of mechanical ventilation	42 days	Rate and length of mechanical Ventilation during follow-up (42 days)
Mortality related to venous thromboembolism	42 days	Mortality related to venous thromboembolism during follow-up (42 days)
Mortality related to arterial thromboembolism	42 days	Mortality related to arterial thromboembolism during follow-up (42 days)
All-cause mortality	42 days	All-cause mortality during follow-up (42 days)
Rate of venous and/ or arterial thromboembolism	42 days	Rate of venous and/ or arterial thromboembolism during follow-up (42 days) Thromboembolisms will be detected by duplex ultrasonography of arms and legs
Cardiac arrest/ CPR	42 days	Cardiac arrest/ CPR during follow-up (42 days)
Rate and length of renal replacement therapy	42 days	Rate and length of renal replacement therapy during follow-up (42 days)
Rehospitalisation	42 days	Rehospitalisation during follow-up (42 days)
Length of initial stay at ICU after application of IMP	42 days	Length of initial stay at ICU after application of IMP during follow-up (42 days)

Trial Locations

Locations (10)

TU München Klinikum rechts der Isar; 🇩🇪 München, Germany

Asklepios Klinik Altona; 🇩🇪 Hamburg, Germany

Asklepios Klinik Barmbek; 🇩🇪 Hamburg, Germany

Universitärsklinikum Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hanover, Germany

Universitätsklinikum Freiburg; 🇩🇪 Freiburg, Germany

Asklepios Klinik St. Georg; 🇩🇪 Hamburg, Germany

UK Aachen; 🇩🇪 Aachen, Germany

Universitätsklinikum Augsburg; 🇩🇪 Augsburg, Germany

Universitätsklinikum Düsseldorf; 🇩🇪 Düsseldorf, Germany