EUCTR2020‐002504‐39‐DE.

Study name	Hamburg edoxaban for anticoagulation in COVID‐19 study
Starting date	10 November 2020
Contact information	Lilli Gerstenmaier    Martinistrasse 64 20251 Hamburg Germany +49040524719216 | regulatory@ctc‐north.com
Methods	Prospective, single‐blind, 2‐armed, parallel‐assignment RCT
Participants	172 participants, ≥ 18 years, female and male Inclusion criteria: Diagnosis of COVID‐19 and hospitalisation on ICU, or Diagnosis of COVID‐19 and hospitalisation on normal ward, or Diagnosis of COVID‐19 and troponin = ULN and/or D‐dimer = 0.5 mg/L Legally effective declaration of informed consent Exclusion criteria: Age < 18 Life expectancy < 3 months before COVID‐19 Resuscitation > 30 min Contraindications against the use of each of the standard LMWH/fondaparinux according to the respective summary of product characteristics 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
Interventions	Experimental: Lixiana Edoxaban ‐ concentration unit: mg milligram(s); concentration number: 60 and 30 Arixtra Fondaparinux sodium ‐ concentration unit: mg milligram(s); concentration number: 7.5 Comparator: Film‐coated tablet; route of administration of the placebo: oral use
Outcomes	Primary Main objective: (i) to evaluate if an intensive anticoagulation strategy using edoxaban on top of standard care of COVID‐19 therapy is superior to standard care (in‐hospital moderate anticoagulation strategy = low‐dose LMWH, ambulatory no anticoagulation, i.e. placebo within this trial) in reduction of morbidity and mortality endpoints in patients with COVID‐19 To assess safety and tolerability of edoxaban and high‐dose LMWH on top of standard care in patients with COVID‐19 Primary end point(s): efficacy Combined endpoint: all‐cause mortality and/or VTE and/or arterial thromboembolism within 42 days Safety endpoints: Rate of SAEs/AEs/suspected unexpected serious adverse reactions in both arms within 42 days Major and clinically relevant non‐major bleeding according ISTH Interruption of therapy due to intolerability to edoxaban New treatment‐emergent AEs (and changes in severity and frequency in these) related to edoxaban Secondary objective: furthermore, secondary objectives intend to evaluate the effect of both treatment regimes with respect to all‐cause mortality, mortality related to VTE and arterial thromboembolism, rate of arterial embolism/VTE, rate and length of mechanical ventilation, length of initial stay at ICU, rehospitalisation, rate and length of renal replacement therapy, cardiac arrest and CPR Time point(s) of evaluation of this end point: 42 days Secondary Secondary end point(s): the secondary efficacy objectives are to compare the active treatment and placebo groups with respect to: All‐cause mortality within 42 days Mortality related to VTE Mortality related to arterial thromboembolism Rate of VTE and/or arterial thromboembolism Rate and length of mechanical ventilation until day 42 Length of initial stay at ICU after application of investigational medicinal product up to a total of 42 days Rehospitalisation within 42 days Rate and length of renal replacement therapy until day 42 Cardiac arrest/CPR until day 42 Further assessment of safety: An expanded safety composite event including death, myocardial infarction, stroke, recurrent hospitalisation, bleeding, acute kidney injury, and gastrointestinal disorders will be collected, analysed and reported. Upon medical need and/or regulatory requirements additional visits may be scheduled. Time point(s) of evaluation of this end point: 42 days
Notes	EUCTR2020‐002504‐39‐DE | No data provided | Source(s) of monetary support: Daiichi Sankyo Europe GmbH; University Medical Center Hamburg‐Eppendorf