Edoxaban in Peripheral Arterial Disease (ePAD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Daiichi Sankyo Inc.
Sponsor:
Collaborator:
UMC Utrecht
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT01802775
First received: February 25, 2013
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Peripheral Arterial Disease
Drug: edoxaban
Drug: Clopidogrel
Drug: Aspirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Parallel-Group, Multi-Center Study Of Adding Edoxaban Or Clopidogrel To Aspirin To Maintain Patency In Subjects With Peripheral Arterial Disease Following Femoropopliteal Endovascular Intervention

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • bleeding events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    The proportion of subjects with major, major or clinically relevant non-major and all bleedings at 6 months.

  • proportion of patients with re-stenosis/re-occlusion [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The difference in proportions of patients with re-stenosis/re-occlusion at the treated segments(s)/s between treatment groups at 6 months.


Secondary Outcome Measures:
  • bleeding events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    The proportion of subjects with major, major or clinically relevant non-major and all bleedings at 6 months will be estimated for each treatment group and summarized with 95% CI. The difference in the proportion between the two groups at each of the time points will be estimated with a 95% confidence interval (CI).

  • any bleeding [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    number of subjects with any bleeding (major, clinically relevant non-major, and minor bleeding) occurring during treatment or within 3 days of interrupting or stopping study drug

  • safety assessments [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    number of clinical and laboratory safety events with description of event including adverse events (AEs), serious adverse events (SAEs), and other events of special interest (i.e., hepatic events).

  • Major Adverse Cardiovascular Events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    number of Major Adverse Cardiovascular Events (MACE) which is a composite of non-fatal myocardial infarction (MI)/non-fatal stroke and death from cardiovascular causes

  • amputations [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    number of amputations and description of event

  • all cause mortality [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    number of all cause mortalities and description of event


Estimated Enrollment: 200
Study Start Date: January 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: edoxaban Drug: Aspirin
Active Comparator: 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).
Drug: Clopidogrel
75mg tablet
Other Name: Plavix
Drug: Aspirin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01802775

Contacts
Contact: Medpace Recruiting Recruitment@Medpace.com

  Show 42 Study Locations
Sponsors and Collaborators
Daiichi Sankyo Inc.
UMC Utrecht
  More Information

No publications provided

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT01802775     History of Changes
Other Study ID Numbers: DU176b-E-U210
Study First Received: February 25, 2013
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Peripheral Arterial Disease
Peripheral Vascular Diseases
Arterial Occlusive Diseases
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Vascular Diseases
Aspirin
Clopidogrel
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antipyretics
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Purinergic Agents
Purinergic Antagonists

ClinicalTrials.gov processed this record on October 23, 2014