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

• ClinicalTrials.gov Identifier: NCT04542408
• Recruitment Status: Recruiting
• First Posted: September 9, 2020
• Last Update Posted: November 18, 2020
• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Information provided by (Responsible Party): Universitätsklinikum Hamburg-Eppendorf

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.

Condition or disease	Intervention/treatment	Phase
Covid19	Drug: Anticoagulation Agents (Edoxaban and/or high dose LMWH); Drug: Low dose Low molecular weight heparin or Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 172 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Hamburg Edoxaban for Anticoagulation in COVID-19 Study
• Actual Study Start Date: November 12, 2020
• Estimated Primary Completion Date: May 31, 2021
• Estimated Study Completion Date: September 30, 2021

Arms and Interventions

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
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

Outcome Measures

Primary Outcome Measures :

1. Combined endpoint: all-cause mortality and/ or venous thromboem-bolism and/ or arterial thromboembolism [ Time Frame: 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 :

1. All-cause mortality [ Time Frame: 42 days ]
   All-cause mortality during follow-up (42 days)
2. Mortality related to venous thromboembolism [ Time Frame: 42 days ]
   Mortality related to venous thromboembolism during follow-up (42 days)
3. Mortality related to arterial thromboembolism [ Time Frame: 42 days ]
   Mortality related to arterial thromboembolism during follow-up (42 days)
4. Rate of venous and/ or arterial thromboembolism [ Time Frame: 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
5. Rate and length of mechanical ventilation [ Time Frame: 42 days ]
   Rate and length of mechanical Ventilation during follow-up (42 days)
6. Length of initial stay at ICU after application of IMP [ Time Frame: 42 days ]
   Length of initial stay at ICU after application of IMP during follow-up (42 days)
7. Rehospitalisation [ Time Frame: 42 days ]
   Rehospitalisation during follow-up (42 days)
8. Rate and length of renal replacement therapy [ Time Frame: 42 days ]
   Rate and length of renal replacement therapy during follow-up (42 days)
9. Cardiac arrest/ CPR [ Time Frame: 42 days ]
   Cardiac arrest/ CPR during follow-up (42 days)

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Stefan Kluge, MD; +49 40 7410 ext 57010; s.kluge@uke.de

Contact: Mahir Karakas, MD; +49 152 22817493; m.karakas@uke.de

Locations

Germany

Universitätsklinikum Düsseldorf; Not yet recruiting

Düsseldorf, Germany

Contact: Bode, MD

Universitätsklinikum Freiburg; Not yet recruiting

Freiburg, Germany

Contact: Hans-Jörg Busch

Marienkrankenhaus; Not yet recruiting

Hamburg, Germany

Contact: Schäfer, MD

Universitärsklinikum Hamburg-Eppendorf; Recruiting

Hamburg, Germany

Contact: Stefan Kluge, MD s.kluge@uke.de

Medizinische Hochschule Hannover; Not yet recruiting

Hanover, Germany

Contact: Tobias Welte, MD

Krankenhaus Köln-Merheim; Not yet recruiting

Köln, Germany

Contact: Christian Karagiannidis, MD

TU München Klinikum rechts der Isar; Not yet recruiting

München, Germany

Contact: Tobias Lahmer

Universitätsklinikum Münster; Not yet recruiting

Münster, Germany

Contact: Hartmut Schmidt, MD

Sponsors and Collaborators

Universitätsklinikum Hamburg-Eppendorf

Investigators

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

More Information

• Responsible Party: Universitätsklinikum Hamburg-Eppendorf
• ClinicalTrials.gov Identifier: NCT04542408
• Other Study ID Numbers: HERO-19
• First Posted: September 9, 2020
• Last Update Posted: November 18, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:

Coagulopathy

Additional relevant MeSH terms:

Heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Edoxaban; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors