Edoxaban in Peripheral Arterial Disease

NCT ID: NCT01802775

Last Updated: 2019-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 203 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-06
• Study Completion Date: 2014-12-03

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

edoxaban/aspirin

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.

Group Type: EXPERIMENTAL

edoxaban

Intervention Type: DRUG

Aspirin

Intervention Type: DRUG

clopidogrel/aspirin

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).

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

75mg tablet

Aspirin

Intervention Type: DRUG

Interventions

edoxaban

Intervention Type: DRUG

Clopidogrel

75mg tablet

Intervention Type: DRUG

Aspirin

Intervention Type: DRUG

Other Intervention Names

Plavix

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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;
• Subjects who received any investigational drug or device within 30 days prior to randomization, or plan to receive such investigational therapy during the study period;
• Subjects previously randomized to an edoxaban (DU-176b) study;
• Women of childbearing potential without proper contraceptive measures (i.e. a method of contraception with a failure rate < 1 % during the course of the study including the observational period) and women who are pregnant or breast feeding;
• Subjects with the following diagnoses or situations:

Active malignancy except for adequately treated non-melanoma skin cancer or other non-invasive or in-situ neoplasm (e.g., cervical cancer in situ); Concurrent treatment with cancer therapy (drugs, radiation, and/or surgery); Other significant active concurrent medical illness or infection; Life expectancy < 12 months;

• Subjects who are unlikely to comply with the protocol (e.g., uncooperative attitude, inability to return for subsequent visits, and/or otherwise considered by the Investigator to be unlikely to complete the study);
• Subjects with any condition that, in the opinion of the Investigator, would place the subject at increased risk of harm if he/she participated in the study;
• History of heparin-induced thrombocytopenia

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UMC Utrecht

OTHER

Sponsor Role: collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Birmingham, Alabama, United States

Phoenix, Arizona, United States

Beverly Hills, California, United States

Los Angeles, California, United States

Orange, California, United States

New Haven, Connecticut, United States

Hollywood, Florida, United States

Jacksonville, Florida, United States

Aurora, Illinois, United States

Iowa City, Iowa, United States

New Orleans, Louisiana, United States

Lewiston, Maine, United States

Boston, Massachusetts, United States

Flint, Michigan, United States

Ypsilanti, Michigan, United States

Teaneck, New Jersey, United States

New York, New York, United States

Raleigh, North Carolina, United States

Wilmington, North Carolina, United States

Cleveland, Ohio, United States

Columbus, Ohio, United States

Camp Hill, Pennsylvania, United States

Columbia, South Carolina, United States

Greenville, South Carolina, United States

Austin, Texas, United States

San Antonio, Texas, United States

Graz, , Austria

Innsbruck, , Austria

Vienna, , Austria

Edgem

Edegem, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Bad Krozingen, , Germany

Leipzig, , Germany

Afula, , Israel

Jerusalem, , Israel

Tel Aviv, , Israel

Tel Litwinsky, , Israel

Rotterdam, , Netherlands

Utrecht, , Netherlands

Bern, , Switzerland

Zurich, , Switzerland

Countries

United States; Austria; Belgium; Germany; Israel; Netherlands; Switzerland

References

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.

Reference Type: DERIVED

PMID: 29552984 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25809373 (View on PubMed)

Other Identifiers

2012-003009-88

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DU176b-E-U210

Identifier Type: -

Identifier Source: org_study_id