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: May 17, 2022
• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Information provided by (Responsible Party): Universitätsklinikum Hamburg-Eppendorf

Tracking Information

• First Submitted Date: September 6, 2020
• First Posted Date: September 9, 2020
• Last Update Posted Date: May 17, 2022
• Actual Study Start Date: November 12, 2020
• Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 6, 2020)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 6, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Hamburg Edoxaban for Anticoagulation in COVID-19 Study
• Official Title: Hamburg Edoxaban for Anticoagulation in COVID-19 Study
• 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Covid19

Intervention

• 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
• 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

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 6, 2020): 172
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2023
• Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

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

• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT04542408
• Other Study ID Numbers: HERO-19
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Universitätsklinikum Hamburg-Eppendorf
• Original Responsible Party: Same as current
• Current Study Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Universitätsklinikum Hamburg-Eppendorf
• Verification Date: May 2022