Edoxaban Treatment in Routine Clinical Practice in Patients With Venous Thromboembolism in Europe (ETNA-VTE)

Non-Interventional Study on Edoxaban Treatment in Routine Clinical Practice in Patients With Venous Thromboembolism in Europe

According to current guidelines, duration of anticoagulant treatment after a venous thromboembolic event varies from 3 months to indefinite treatment depending on the estimated risks of venous thromboembolism (VTE) recurrence and bleeding. Current data for edoxaban are limited to a maximum treatment duration of 12 months (Hokusai-VTE; N Engl J Med. 2013; 369:1406-15).

Therefore, this study aims to gather further insight into efficacy (i.e. symptomatic recurrent VTE) and safety (i.e. bleeding events, liver adverse events, all-cause mortality and other drug related adverse events) of extended treatment with edoxaban up to 18 months in an unselected patient population in routine clinical practice.

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: Edoxaban

Detailed Description

Real-world evidence data in routine clinical practice use of edoxaban up to 18 months will be collected in 2,700 patients, treated by specialized as well as non-specialized physicians in hospitals and office based centres in 8 European countries. Patients from different countries and care settings (primary care and secondary care, different specialties) will be enrolled in this post-authorization safety study. Documentation of baseline and follow up information at 1, 3, 6, 12, and 18 months (only when available) will be collected. In addition, recurrence of symptomatic VTE and death will be captured retrospectively at time point of Last Patient Out per country.

Patients who discontinue permanently edoxaban during the observational period will be followed up according to the same scheme.

• Study Type: Observational
• Enrollment (Actual): 2809

Contacts and Locations

Study Locations

• Germany
  • Germering, Germany, 82110
    • International Clinical Research GmbH

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All patients with established initial or recurrent acute symptomatic VTE (distal or proximal deep vein thrombosis/pulmonary embolism) treated with edoxaban according to the Summary of Product Characteristics (SmPC). To ensure that the physician's prescribing behaviour will not be influenced, patients may only be included after the treating physician has made the clinical decision to prescribe edoxaban. Patients must have provided written informed consent for participation in the study (ICF) and should not participate simultaneously in any interventional study.

Description

Inclusion Criteria:

• Established acute initial or recurrent VTE
• Clinical decision for treatment with edoxaban is made at the time of enrollment
• Written informed consent for participation in the study (ICF)
• Not simultaneously participating in any interventional study

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients treated with Edoxaban; Patients with established initial or recurrent acute symptomatic VTE treated with edoxaban according to the Summary of Product Characteristics (SmPC). Physician's prescribing behaviour will not be influenced, patients may only be included after the treating physician has made the clinical decision to prescribe edoxaban.	Drug: Edoxaban; Prescribed according to approved label; Other Names: Lixiana

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With At Least 1 Symptomatic Venous Thromboembolism Recurrence - Overall	Descriptive statistics were used to report the number of participants with at least 1 symptomatic VTE recurrence. Recurrent VTE events were based on adjudicated events.	Baseline up to end of observation period (18 months)
Number of Participants With Bleeding Events (Adjudicated) While On Edoxaban Treatment	Descriptive statistics were used to report the number of participants with bleeding events.	Baseline up to end of observation period (18 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing At Least 1 Real World Safety Event - Overall	Descriptive statistics were used to report the number of participants experiencing recurrent VTE and at least 1 real world safety event. VTE recurrence data were reported by recurrent deep vein thrombosis (DVT), recurrent pulmonary embolism (PE) with DVT, and recurrent PE only. Recurrent VTE events were based on adjudicated events. Real world safety events included all-cause death, cardiovascular (CV)-related death, VTE-related death, stroke, systemic embolic event, and hospitalization related to CV.	Baseline up to end of observation period (18 months)
Number of Participants With At Least 1 Symptomatic Venous Thromboembolism Recurrence - On Edoxaban Treatment	Descriptive statistics were used to report the number of participants with overall symptomatic VTE recurrence. VTE recurrence data were further reported by recurrent deep venous thrombosis (DVT), recurrent pulmonary embolism (PE) with deep venous thrombosis (DVT), and recurrent PE only. Recurrent VTE events were based on adjudicated events.	Baseline up to end of observation period (18 months)
Total Number of Venous Thromboembolism Recurrences By Type - Overall	Descriptive statistics were used to describe the number of VTE events reported by the patient.	Baseline up to end of observation period (18 months)
Duration of Venous Thromboembolism Recurrences, by Type - Overall	Descriptive statistics were used to assess the duration of VTE events reported by the patient.	Baseline up to end of observation period (18 months)
Total Number of Venous Thromboembolism Recurrences (On Edoxaban Treatment)	Descriptive statistics were used to assess the number of recurrent VTE events reported by the patient.	Baseline up to end of observation period (18 months)
Duration of Venous Thromboembolism Events (On Edoxaban Treatment)	Descriptive statistics were used to assess the duration of VTE events reported by the patient.	Baseline up to end of observation period (18 months)
Number of Participants With Risk Factors for Thromboembolic Events at Baseline	Descriptive statistics were used to assess the number of participants with risk factors for thromboembolic events.	at Baseline
Duration of Edoxaban Treatment	Descriptive statistics were used to report the duration of edoxaban treatment.	Baseline up to end of observational period (18 months)
Number of Stroke Events	Descriptive statistics were used to report the number of stroke events.	Baseline up to end of observation period (18 months)
Number of Systemic Embolic Events - Overall	Descriptive statistics were used to report the number of systemic embolic events (SEE).	Baseline up to end of observation period (18 months)
Overview of Participants With Adverse Drug Reactions	Descriptive statistics were used to report an overview of participants with adverse drug reactions (ADR). ADRs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 20.1.	Baseline up to end of observation period (18 months)
Number of Participants With Adverse Drug Reactions by Preferred Term (≥0.2%)	Adverse drug reactions were reported and coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 20.1.	Baseline up to end of observational period (18 months)
Number of Participants With Pre-defined Adverse Drug Reactions	Descriptive statistics were used to report the number of participants with pre-defined adverse drug reactions (ADR). ADRs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 20.1.	Baseline up to end of observation period (18 months)

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

Publications and helpful links

General Publications

• Hokusai-VTE Investigators, Buller HR, Decousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. doi: 10.1056/NEJMoa1306638. Epub 2013 Aug 31. Erratum In: N Engl J Med. 2014 Jan 23;370(4):390.
• Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Spinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369(22):2093-104. doi: 10.1056/NEJMoa1310907. Epub 2013 Nov 19.
• Cohen AT, Hoffmann U, Hainaut P, Gaine S, Ay C, Coppens M, Schindewolf M, Jimenez D, Bruggenjurgen B, Levy P, Laeis P, Fronk EM, Zierhut W, Malzer T, Manu MC, Reimitz PE, Bramlage P, Agnelli G; ETNA-VTE-Europe investigators. ETNA VTE Europe: A contemporary snapshot of patients treated with edoxaban in clinical practice across eight European countries. Eur J Intern Med. 2020 Dec;82:48-55. doi: 10.1016/j.ejim.2020.08.014. Epub 2020 Aug 18.
• Cohen AT, Ay C, Hainaut P, Decousus H, Hoffmann U, Gaine S, Coppens M, da Silva PM, Castro DJ, Amann-Vesti B, Bruggenjurgen B, Levy P, Bastida JL, Vicaut E, Laeis P, Fronk EM, Zierhut W, Malzer T, Bramlage P, Agnelli G; ETNA-VTE-Europe investigators. Design and rationale of the non-interventional, edoxaban treatment in routiNe clinical prActice in patients with venous ThromboEmbolism in Europe (ETNA-VTE-Europe) study. Thromb J. 2018 May 1;16:9. doi: 10.1186/s12959-018-0163-7. eCollection 2018. Erratum In: Thromb J. 2018 May 31;16:18.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2016
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: October 24, 2016
• First Submitted That Met QC Criteria: October 24, 2016
• First Posted (Estimate): October 25, 2016

Study Record Updates

• Last Update Posted (Actual): May 2, 2022
• Last Update Submitted That Met QC Criteria: February 18, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Efficacy/Safety; Real World Evidence; Edoxaban; Post-Authorisation Safety Study
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Edoxaban
• Other Study ID Numbers: DSE-EDO-05-14-EU

Plan for Individual participant data (IPD)

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