Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale (DEFENSE-PFO)

June 28, 2017 updated by: Jae-Kwan Song

Device Closure Versus Medical Therapy for Secondary Prevention in Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale : DEFENSE-PFO

Background and hypothesis:

The appropriate treatment strategy for secondary stroke prevention in patients with cryptogenic stroke and patent foramen ovale (PFO) remains challenging. Clinical and anatomical variables reported to be risk factors associated with stroke recurrence include older age, large PFO, large right-to-left shunting, and combined atrial septal aneurysm (ASA), which, however, were not confirmed by other studies. The investigators hypothesized that percutaneous closure of PFO could be an effective option for secondary prevention in cryptogenic stroke patients with high-risk PFO.

Trial Objective:

The primary objective of this study is to assess whether percutaneous device closure of PFO is superior to conventional antithrombotic treatment in preventing stroke recurrence in the cryptogenic stroke patients with high-risk PFO.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Selection of patients:

Among cryptogenic stroke patients, patients who was identified as high risk PFO which might be defined as high-risk of recurrence (PFO size ≥ 2 mm or atrial septal aneurysm or hypermobility by TEE) will be randomized 1:1 to :a) Device closure using Amplatzer device vs. b) standard medical therapy alone. All patients will be followed for at least 2 years.

Echocardiography Findings for high-risk PFO Digitally, stored transesophageal echocardiographic images were reviewed and analyzed by an investigator. Using calipers, the PFO size was measured as the maximum separation of the septum primum from the septum secundum. ASA or hypermobility was defined as ≥ 10 mm of phasic septal excursion either into the atrium or a sum total excursion of ≥ 15 mm during the cardiorespiratory cycle, with a base of ≥ 15 mm.

Web-based 1:1 blinded randomization for

  • Experimental Percutaneous Device Closure using AMPLATZER PFO Occluder
  • Active Comparator Standard Medical management using anti-coagulant therapy (at least 3 or 6 months) Study Endpoints

  • Primary outcome

    • Recurrence of nonfatal stroke/vascular death/TIMI-major bleeding

  • Secondary outcome

    • Recurrent nonfatal stroke
    • Vascular death
    • Major bleeding associated with medication
    • Asymptomatic recurrent ischemic stroke on follow-up MR
    • Complete closure of the defect demonstrated by TEE and bubble study (device group) Frequency of residual shunt, (in)correct device position, need for implantation of second device and peri-procedural complications
    • Procedure related complications
    • Medication related complications

Study Type

Interventional

Enrollment (Anticipated)

210

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Busan, Korea, Republic of
        • Recruiting
        • Yangsan Busan University Hospital
        • Contact:
          • Yong-Hyung Park, MD, PhD
          • Phone Number: 82-2-3010-3150
          • Email: nadroj@chol.com
        • Principal Investigator:
          • Yong-Hyun Park, MD, PhD
      • Daejeon, Korea, Republic of
        • Recruiting
        • Chungnam National University Hospital
        • Contact:
        • Principal Investigator:
          • Jae Hwan Lee, MD, PhD
      • Gangneung, Korea, Republic of
        • Recruiting
        • Gang Neung Asan Hospital
        • Contact:
        • Principal Investigator:
          • Sang-Sig Jeong, MD, PhD
      • Ulsan, Korea, Republic of
        • Recruiting
        • Ulsan University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects who have had a cryptogenic stroke within the previous 3 months, radiologically verified
  • Subjects who have been diagnosed with a high-risk* Patent Foramen Ovale (PFO), echocardiographically verified (*PFO size ≥ 2 mm or atrial septal aneurysm or hypermobility by TEE)
  • Subjects willing to participate in follow-up visits
  • Absence of other potential causes of stroke

Exclusion Criteria:

  • Any identifiable cause of thromboembolic cause other than PFO
  • Subjects with intracardiac thrombus or tumor, dilated cardiomyopathy, prosthetic heart valve or mitral stenosis, endocarditis
  • Subjects with significant atherosclerosis or dissection of the aorta, collagen vascular disease, arteritis, vasculitis and coagulopathy
  • Subjects who have an acute or recent (within 6 months) myocardial infarction or unstable angina
  • Subjects who have a non-vascular origin of the neurological symptoms after brain imaging (CT scan or MRI)
  • History of intracranial bleeding, confirmed arterio-venous malformation,aneurysm or uncontrolled coagulopathy
  • Pre-existing neurological disorders or intracranial disease, e.g. multiple sclerosis
  • Subjects with left ventricular aneurysm or akinesis
  • Subjects with atrial fibrillation/atrial flutter (chronic or intermittent)
  • Subjects with another source of right to left shunt identified at baseline, including an atrial septal defect and/or fenestrated septum
  • Subjects who could not undergo the TEE examination
  • Subjects with contraindication to aspirin or Clopidogrel therapy
  • Pregnant or desire to become pregnant within the next year
  • Subjects who have a underlying malignancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Medication
Anticoagulation, Antiplatelet agent
Drug: Standard medical treatment
Standard Medical management using anti-coagulant therapy
ACTIVE_COMPARATOR: Device closure
Amplatzer PFO occluder device
Device: Device closure
PFO Amplatzer device closure
Other Names:
  • PFO Amplatzer device

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Recurrence of nonfatal stroke / vascular death / TIMI-major bleeding
Time Frame: 2-year
2-year

Secondary Outcome Measures

Outcome Measure
Time Frame
Recurrent nonfatal stroke
Time Frame: 2-year
2-year
Vascular death
Time Frame: 2-year
2-year
Major bleeding associated with medication
Time Frame: 2-year
2-year
Asymptomatic recurrent ischemic stroke on follow-up MR
Time Frame: 2-year
2-year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jae-Kwan Song

Investigators

  • Principal Investigator: Jae-Kwan Song, MD, PhD, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2012

Primary Completion (ANTICIPATED)

February 1, 2020

Study Completion (ANTICIPATED)

February 1, 2020

Study Registration Dates

First Submitted

February 26, 2012

First Submitted That Met QC Criteria

March 7, 2012

First Posted (ESTIMATE)

March 12, 2012

Study Record Updates

Last Update Posted (ACTUAL)

June 29, 2017

Last Update Submitted That Met QC Criteria

June 28, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011-0553

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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