Hamburg Edoxaban for Anticoagulation in COVID-19 Study (HERO-19)

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany
    • UK Aachen
  • Augsburg, Germany
    • Universitätsklinikum Augsburg
  • Düsseldorf, Germany
    • Universitätsklinikum Düsseldorf
  • Freiburg, Germany
    • Universitätsklinikum Freiburg
  • Hamburg, Germany
    • Asklepios Klinik St. Georg
  • Hamburg, Germany
    • Asklepios Klinik Altona
  • Hamburg, Germany
    • Universitärsklinikum Hamburg-Eppendorf
  • Hamburg, Germany
    • Asklepios Klinik Barmbek
  • Hanover, Germany
    • Medizinische Hochschule Hannover
  • München, Germany
    • TU München Klinikum rechts der Isar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intensive anticoagulation strategy; 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); 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
Other: Moderate anticoagulation strategy; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Investigators: Principal Investigator: Stefan Kluge, MD, Universitätsklinikum Hamburg-Eppendorf

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Actual): September 6, 2022
• Study Completion (Actual): January 15, 2023

Study Registration Dates

• First Submitted: September 6, 2020
• First Submitted That Met QC Criteria: September 6, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 21, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Coagulopathy
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Heparin; Edoxaban; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Anticoagulants
• Other Study ID Numbers: HERO-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No