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

This study is currently recruiting participants.
Verified August 2012 by CardioVascular Research Foundation, Korea
Sponsor:
Information provided by (Responsible Party):
Duk-Woo Park, CardioVascular Research Foundation, Korea
ClinicalTrials.gov Identifier:
NCT01550588
First received: February 26, 2012
Last updated: August 8, 2012
Last verified: August 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Patent Foramen Ovale
 Device: Device closure
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: Device Closure Versus Medical Therapy for Secondary Prevention in Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale : DEFENSE-PFO

Further study details as provided by CardioVascular Research Foundation, Korea:

Primary Outcome Measures:
  • Recurrence of nonfatal stroke / vascular death / TIMI-major bleeding [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Recurrent nonfatal stroke [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
  • Vascular death [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
  • Major bleeding associated with medication [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
  • Asymptomatic recurrent ischemic stroke on follow-up MR [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 210
Study Start Date: February 2012
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Medication
Anticoagulation, Antiplatelet agent
Active Comparator: Device closure
Amplatzer PFO occluder device
 Device: Device closure
PFO Amplatzer device closure
Other Name: PFO Amplatzer device

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
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01550588

Contacts
Contact: Jae-Kwan Song, MD, PhD (82-2)-3010-3155 jksong@amc.seoul.kr
Contact: Jong-Young Lee, MD, PhD 82-2-3010-3061 jyleeheart@amc.seoul.kr

Locations
Korea, Republic of
YangSan Busan University Hospital Recruiting
Busan, Korea, Republic of
Contact: Yong-Hyung Park, MD, PhD     82-2-3010-3150     nadroj@chol.com    
Principal Investigator: Yong-Hyun Park, MD, PhD            
Chungnam National University Hospital Recruiting
Daejeon, Korea, Republic of
Contact: Jae Hwan Lee, Md, PhD     82-3010-3162     myheart@cnu.ac.kr    
Principal Investigator: Jae Hwan Lee, MD, PhD            
Gang Neung Asan Hospital Recruiting
Gangneung, Korea, Republic of
Contact: Sang-Sig Jeong, MD, PhD     82-2-3010-3150     sscheng@gnah.co.kr    
Principal Investigator: Sang-Sig Jeong, MD, PhD            
Ulsan University Hospital Recruiting
Ulsan, Korea, Republic of
Contact: Eun-Seok Shin, Md, PhD     82-3010-3155     jksong@amc.seoul.kr    
Principal Investigator: Eun-Seok Shin, MD, PhD            
Sponsors and Collaborators
Duk-Woo Park
Investigators
Principal Investigator: Jae-Kwan Song, MD, PhD Department of medicine, Asan Medical Center, University of Ulsan College of Medicine
  More Information

No publications provided

Responsible Party: Duk-Woo Park, Professor, CardioVascular Research Foundation, Korea
ClinicalTrials.gov Identifier: NCT01550588     History of Changes
Other Study ID Numbers: 2011-0553
Study First Received: February 26, 2012
Last Updated: August 8, 2012
Health Authority: Korea: Institutional Review Board

Keywords provided by CardioVascular Research Foundation, Korea:
PFO
Stroke

Additional relevant MeSH terms:
Foramen Ovale, Patent
Heart Septal Defects, Atrial
Stroke
Heart Septal Defects
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
 Heart Diseases
Congenital Abnormalities
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on May 23, 2013