Edoxaban in Peripheral Arterial Disease

NCT01802775 | Completed Phase 2 Results

• 2 other identifiers: DU176b-E-U2102012-003009-88
• Study Type: interventional
• Target: 203
• Locations: 7 countries
• Sites: 42

Brief Summary

This study is a randomized, open-label, blinded endpoint, parallel-group, active-control, multi-center, proof-of-concept study in subjects with Peripheral Arterial Disease (PAD), designed to assess the safety and potential efficacy of adding edoxaban to aspirin following femoropopliteal endovascular intervention, with or without stent placement, relative to current treatment practice with clopidogrel and aspirin.

Conditions

Peripheral Arterial Disease

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Clinically Relevant Bleeding During Treatment

  Percentage of participants with clinically relevant bleeding, defined as major bleeding or clinical relevant non-major bleeding, in the on-treatment period based on International Society of Thrombosis and Haemostasis (ISTH)

  at 3 months

• Percentage of Participants With First Re-stenosis / Re-occlusion

  Percentage of participants with re-stenosis/re-occlusion during treatment within 6 months - only the first occurrence of re-stenosis / re-occlusion was counted for each participant

  within 6 months

Secondary Outcomes (4)

• Percentage of Participants With Major, Clinically Relevant Non-major (CRNM), and Minor Bleeding During Treatment

  within 3 months

• Safety Assessments

  within 6 months

• Number of Adjudicated Major Adverse Cardiovascular Events During the Overall Study Period

  within 6 months

• Number of Participants With Amputations

  within 6 months

Study Arms (2)

edoxaban/aspirin

EXPERIMENTAL

Open label edoxaban will be provided. Subjects randomized to this treatment arm will receive edoxaban 60 mg once daily (QD) (two 30 mg tablets) for a total of approximately 3 months on a background of aspirin 100 mg QD.

Drug: edoxaban; Drug: Aspirin

clopidogrel/aspirin

ACTIVE COMPARATOR

Open label clopidogrel will be provided. Subjects randomized to this treatment arm will receive clopidogrel 75 mg QD (one 75 mg tablet) for a total of approximately 3 months on a background of aspirin 100 mg QD. A loading dose of clopidogrel 300 mg (four 75mg tablets) will be given to subjects as the first dose as early as possible after adequate hemostasis (i.e., within 4 hours of hemostasis).

Drug: Clopidogrel; Drug: Aspirin

Interventions

edoxaban DRUG

edoxaban/aspirin

Clopidogrel DRUG

75mg tablet

Also known as: Plavix

clopidogrel/aspirin

Aspirin DRUG

clopidogrel/aspirin; edoxaban/aspirin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects older than the minimum legal adult age (country specific);
• Rutherford stages 2-5 provided there are no ulcerations on the heel and/or exposed tendon and/or bone;
• Superficial femoral above knee-popliteal ( 3 cm proximal to the medial femoral condyle) lesion and ≥ 50% stenosis or occlusion;
• At least one run-off vessel to the foot with or without additional endovascular intervention;
• Successful intervention, defined as angiographic confirmation of ≤ 30% residual stenosis and absence of flow limiting dissection;
• Adequate hemostasis at the vascular access site within 24 hours of intervention;
• A subject is also eligible if they have undergone additional successful endovascular intervention(s) during the index intervention;
• Able to provide signed informed consent.

You may not qualify if:

• Calculated Creatinine Clearance \< 30 ml/min;
• Femoral or popliteal aneurysm;
• Adjunctive use of thrombolytics;
• Any extravasation or distal embolization not successfully treated;
• Uncontrolled hypertension as judged by the investigator (e.g., systolic blood pressure \> 170 mmHg or diastolic blood pressure \> 100 mmHg despite antihypertensives);
• Aspirin intolerance;
• Clopidogrel intolerance;
• Contraindication for anticoagulants or antiplatelets and any other contraindication listed in the local labeling of aspirin and/or clopidogrel;
• Active bleeding or known high risk for bleeding or history of intracranial, or spontaneous intraocular, spinal retroperitoneal or intra-articular bleeding; overt gastrointestinal (GI) bleeding or active ulcer within the previous year;
• Subjects receiving dual antiplatelet or anticoagulant therapy at the time of randomization; subjects receiving pre-interventional loading dose of clopidogrel or other P2Y12 receptor antagonists;
• Treatment with cilostazol within 24 hours of randomization;
• Subjects receiving prohibited concomitant medications \[fibrinolytics, chronic use of non steroidal anti-inflammatory drugs (NSAIDS) \> 4 days per week, and oral or parenteral non-aspirin NSAIDs and strong P-gp inhibitors\];
• Prior stroke or myocardial infarction (MI) or acute coronary syndrome within 3 months;
• Chronic liver disease \[alanine transaminase (ALT) and/or aspartate transaminase (AST) ≥ 2 × upper limit of normal; total bilirubin (TBL) ≥ 1.5 × upper limit of normal\]; however, subjects whose elevated TBL is due to known Gilbert"s syndrome may be included in the study;
• Prior history of a positive test for Hepatitis B antigen or Hepatitis C antibody;

Sponsors & Collaborators

• Daiichi Sankyo: lead
• UMC Utrecht: collaborator

Study Sites (42)

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Birmingham, Alabama, United States

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Phoenix, Arizona, United States

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Beverly Hills, California, United States

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Los Angeles, California, United States

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Orange, California, United States

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New Haven, Connecticut, United States

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Hollywood, Florida, United States

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Jacksonville, Florida, United States

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Aurora, Illinois, United States

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Iowa City, Iowa, United States

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New Orleans, Louisiana, United States

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Lewiston, Maine, United States

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Boston, Massachusetts, United States

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Flint, Michigan, United States

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Ypsilanti, Michigan, United States

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Teaneck, New Jersey, United States

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New York, New York, United States

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Raleigh, North Carolina, United States

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Wilmington, North Carolina, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Camp Hill, Pennsylvania, United States

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Columbia, South Carolina, United States

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Greenville, South Carolina, United States

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Austin, Texas, United States

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San Antonio, Texas, United States

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Graz, Austria

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Innsbruck, Austria

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Vienna, Austria

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Edgem

Edegem, Belgium

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Ghent, Belgium

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Leuven, Belgium

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Bad Krozingen, Germany

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Leipzig, Germany

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Afula, Israel

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Jerusalem, Israel

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Tel Aviv, Israel

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Tel Litwinsky, Israel

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Rotterdam, Netherlands

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Utrecht, Netherlands

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Bern, Switzerland

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Zurich, Switzerland

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Related Publications (2)

• Moll F, Baumgartner I, Jaff M, Nwachuku C, Tangelder M, Ansel G, Adams G, Zeller T, Rundback J, Grosso M, Lin M, Mercur MF, Minar E; ePAD Investigators. Edoxaban Plus Aspirin vs Dual Antiplatelet Therapy in Endovascular Treatment of Patients With Peripheral Artery Disease: Results of the ePAD Trial. J Endovasc Ther. 2018 Apr;25(2):158-168. doi: 10.1177/1526602818760488.

  PMID: 29552984 DERIVED

• Tangelder MJ, Nwachuku CE, Jaff M, Baumgartner I, Duggal A, Adams G, Ansel G, Grosso M, Mercuri M, Shi M, Minar E, Moll FL. A review of antithrombotic therapy and the rationale and design of the randomized edoxaban in patients with peripheral artery disease (ePAD) trial adding edoxaban or clopidogrel to aspirin after femoropopliteal endovascular intervention. J Endovasc Ther. 2015 Apr;22(2):261-8. doi: 10.1177/1526602815574687.

  PMID: 25809373 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

edoxaban; Clopidogrel; Aspirin

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Clinical Trial Information
• Organization: Daiichi Sankyo Development Inc.

info@dsd-eu.com

+44 1753482800

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2013
• First Posted: March 1, 2013
• Study Start: February 6, 2013
• Primary Completion: December 3, 2014
• Study Completion: December 3, 2014
• Last Updated: February 26, 2019
• Results First Posted: January 12, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (26); IL (4); CH (2); NL (2); BE (3); AU (3); DE (2)