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Edoxaban Treatment Versus Vitamin K Antagonist in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention (ENTRUST-AF-PCI)

This study is currently recruiting participants.
Verified November 2017 by Daiichi Sankyo, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02866175
First Posted: August 15, 2016
Last Update Posted: November 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.
  Purpose
There are insufficient data on the safety and efficacy of edoxaban plus antiplatelet therapy in subjects with atrial fibrillation AF following percutaneous intervention PCI with stenting. This study is designed to evaluate the safety and to explore the efficacy of an edoxaban-based antithrombotic regimen versus a vitamin K antagonist VKA-based antithrombotic regimen in subjects with AF following PCI with stent placement. Bleeding is a central safety outcome in cardiovascular clinical trials, especially for antithrombotic strategies and invasive procedures.

Condition Intervention Phase
Atrial Fibrillation Drug: Edoxaban Drug: Clopidogrel Drug: Prasugrel Drug: ticagrelor Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of the Safety and Efficacy of an Edoxaban-based Compared to a Vitamin K Antagonist-based Antithrombotic Regimen in Subjects With Atrial Fibrillation Following Successful Percutaneous Coronary Intervention (PCI) With Stent Placement.

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo, Inc.:

Primary Outcome Measures:
  • Number of participants with Major or Clinically Relevant Non-major Bleeding defined by International Society on Thrombosis and Haemostasis (ISTH) [ Time Frame: day 1 to 12 months ]

Secondary Outcome Measures:
  • Number of participants with Composite of cardiovascular (CV) death, stroke, systemic embolic events (SEE), myocardial infarction (MI) and definite stent thrombosis [ Time Frame: day 1 to 12 months ]
  • Number of participants with Major Bleeding defined by ISTH [ Time Frame: day 1 to 12 months ]
  • Number of participants with Net Clinical Benefit (NCB) [ Time Frame: day 1 to 12 months ]
    Net Clinical Benefit (NCB) is defined as the composite of CV death, stroke, SEE, MI, definite stent thrombosis along with ISTH-defined major bleeding


Estimated Enrollment: 1500
Actual Study Start Date: February 24, 2017
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: edoxaban
Edoxaban 60 mg once-daily or 30 mg once-daily in selected subjects
Drug: Edoxaban
Edoxaban 60 mg once-daily or 30 mg once-daily in selected subjects
Other Name: Savaysa
Active Comparator: vitamin k antagonist
Clopidogrel 75 mg once-daily (or in the presence of a documented clinical need prasugrel [5mg or 10 mg once-daily] or ticagrelor [90 mg twice-daily] may be used).
Drug: Clopidogrel
Clopidogrel 75 mg once-daily
Other Name: Plavix
Drug: Prasugrel
prasugrel 5mg or 10 mg once-daily
Other Name: Effient
Drug: ticagrelor
ticagrelor 90 mg twice-daily

  Eligibility

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • OAC indication for atrial fibrillation for a period of at least 12 months following successful PCI with stenting.

Eligibility is assessed 4 hours after sheath removal and within 5 days after successful PCI with stent placement. If a staged PCI is planned, eligibility is assessed after completion of the last stage.

Successful PCI definition:

The success of a PCI procedure is defined by 2 interrelated components: angiographic findings, procedural / clinical outcomes as detailed below:

Angiographic Success A minimum stenosis diameter of < 20% (as visually assessed by angiography - residual blockage or stenosis reduced to less than 20% of the artery's diameter).

Sufficient enlargement of the lumen at the target site to improve coronary artery blood flow with final TIMI flow grade 3 (visually assessed by angiography), without occlusion of a significant side branch, flow-limiting dissection, distal embolization, or angiographic thrombus.

Procedural Success No major in-hospital clinical complications(e.g. ongoing ISTH major or clinical relevant non-major procedural bleeding at the time of randomization, stroke, emergency CABG).

In summary, a clinically successful PCI requires both anatomic and procedural success along with relief of signs and/or symptoms of myocardial ischemia at the time of randomization.

Exclusion Criteria:

  • Bleeding risks or systemic conditions
  • Known bleeding diathesis, including but not limited to,

    1. Uncontrolled active bleeding, encompassing both ISTH major and clinically relevant non-major bleeding, preceding randomization.

      Lesion or condition, if considered to be a significant risk for major bleeding. This may include but is not limited to: unresolved gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding (e.g. malignancies with metastasis), recent unresolved brain or spinal injury, recent brain, spinal or ophthalmic surgery, any intracranial hemorrhage, known or suspected esophageal varices, arteriovenous malformations, vascular aneurysms (of more than 3.5 cm) or major intraspinal or intracerebral vascular abnormalities.

    2. Medication-related
  • INR > 2.5 (the subject can be reconsidered at a later time, but within 5 days of sheath removal).
  • Contraindication to edoxaban, VKA, ASA and/or P2Y12 antagonists;
  • Concomitant treatment with other antithrombotic agents, fibrinolytic therapy and chronic nonsteroidal anti-inflammatory drugs (NSAIDs).

Concomitant conditions and therapies

  • Critically ill or hemodynamically unstable subjects (at the time of randomization) including:

    1. cardiogenic shock or acute decompensated heart failure, with the requirement for vasopressor agents or inotropic support or mechanical support to support circulation
    2. respiratory failure requiring endotracheal intubation and mechanical ventilation.
  • Any prior mechanical valvular prosthesis;
  • Planned coronary or vascular intervention or major surgery within 12 months; Randomization must be deferred to the last stage in a multistep, multivessel PCI procedure;
  • Moderate or severe mitral stenosis;
  • Ischemic stroke within 2 weeks prior to randomization;
  • Uncontrolled severe hypertension with a systolic blood pressure (BP) ≥180 mmHg and/or diastolic BP ≥ 120 mmHg;
  • End stage renal disease (ESRD) (CrCL < 15 mL/min or on dialysis);
  • Known abnormal liver function prior to randomization (incl. hepatic disease or biochemical evidence of significant liver derangement known prior to randomization).

Other exclusion criteria

  • Any of the following abnormal local laboratory results prior to randomization:

    1. Platelet count < 50 x109/L
    2. Hemoglobin < 8 mg/dL
  • Unable to provide written IC;
  • Female subjects of childbearing potential without using highly effective contraception (female of childbearing potential is defined as one who has not been postmenopausal for at least one year, or has not been surgically sterilised, or has not had a hysterectomy at least three months prior to the start of this study). Females taking oral contraceptives should have been on therapy for at least three months. Adequate contraceptives include: Combined (estrogen and progestogen containing) oral, intravaginal, transdermal, hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; sexual abstinence;
  • Pregnant or breast-feeding subjects;
  • Assessment that the subject is not likely to comply with the study procedures or have complete follow-up;
  • Participating in another clinical trial that potentially interferes with the current study;
  • Previous randomization in this study;
  • Active on prescription drug abuse and addiction; abuse of illicit substances (i.e. marijuana, cocaine, methamphetamine, heroin) and alcohol abuses during the last 12 months according to the judgement of the investigator;
  • Life expectancy < 12 months.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02866175


  Show 233 Study Locations
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
Study Chair: Pascal Vranckx, MD Hartcentrum Hasselt
Study Chair: Andreas Gotte, Prof., MD Medizinische Klinik II
  More Information

Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT02866175     History of Changes
Other Study ID Numbers: DSE-EDO-01-15-EU
First Submitted: August 10, 2016
First Posted: August 15, 2016
Last Update Posted: November 7, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at http://www.clinicalstudydatarequest.com. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Studies for which the medicine and indication have received EU and US marketing approval on or after 01 January 2014 or by the US or EU Health Authorities when regulatory submissions in both 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 and the European Union 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.
URL: https://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Daiichi Sankyo, Inc.:
percutaneous intervention
vitamin K antagonist

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Vitamins
Vitamin K
Clopidogrel
Prasugrel Hydrochloride
Ticagrelor
Edoxaban
Micronutrients
Growth Substances
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antifibrinolytic Agents
Fibrin Modulating Agents
Hemostatics
Coagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors