Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale (DEFENSE-PFO)
Primary Purpose
Patent Foramen Ovale
Status
Unknown status
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Device closure
Standard medical treatment
Sponsored by
About this trial
This is an interventional prevention trial for Patent Foramen Ovale focused on measuring PFO, Stroke
Eligibility 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
Sites / Locations
- YangSan Busan University HospitalRecruiting
- Chungnam National University HospitalRecruiting
- Gang Neung Asan HospitalRecruiting
- Ulsan University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Medication
Device closure
Arm Description
Anticoagulation, Antiplatelet agent
Amplatzer PFO occluder device
Outcomes
Primary Outcome Measures
Recurrence of nonfatal stroke / vascular death / TIMI-major bleeding
Secondary Outcome Measures
Recurrent nonfatal stroke
Vascular death
Major bleeding associated with medication
Asymptomatic recurrent ischemic stroke on follow-up MR
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01550588
Brief Title
Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale (DEFENSE-PFO)
Official Title
Device Closure Versus Medical Therapy for Secondary Prevention in Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale : DEFENSE-PFO
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Unknown status
Study Start Date
February 2012 (undefined)
Primary Completion Date
February 2020 (Anticipated)
Study Completion Date
February 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jae-Kwan Song
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Patent Foramen Ovale
Keywords
PFO, Stroke
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
210 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Medication
Arm Type
Placebo Comparator
Arm Description
Anticoagulation, Antiplatelet agent
Arm Title
Device closure
Arm Type
Active Comparator
Arm Description
Amplatzer PFO occluder device
Intervention Type
Device
Intervention Name(s)
Device closure
Other Intervention Name(s)
PFO Amplatzer device
Intervention Description
PFO Amplatzer device closure
Intervention Type
Drug
Intervention Name(s)
Standard medical treatment
Intervention Description
Standard Medical management using anti-coagulant therapy
Primary Outcome Measure Information:
Title
Recurrence of nonfatal stroke / vascular death / TIMI-major bleeding
Time Frame
2-year
Secondary Outcome Measure Information:
Title
Recurrent nonfatal stroke
Time Frame
2-year
Title
Vascular death
Time Frame
2-year
Title
Major bleeding associated with medication
Time Frame
2-year
Title
Asymptomatic recurrent ischemic stroke on follow-up MR
Time Frame
2-year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jae-Kwan Song, MD, PhD
Phone
(82-2)-3010-3155
Email
jksong@amc.seoul.kr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jae-Kwan Song, MD, PhD
Organizational Affiliation
Department of medicine, Asan Medical Center, University of Ulsan College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
YangSan Busan University Hospital
City
Busan
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yong-Hyung Park, MD, PhD
Phone
82-2-3010-3150
Email
nadroj@chol.com
First Name & Middle Initial & Last Name & Degree
Yong-Hyun Park, MD, PhD
Facility Name
Chungnam National University Hospital
City
Daejeon
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jae Hwan Lee, Md, PhD
Phone
82-3010-3162
Email
myheart@cnu.ac.kr
First Name & Middle Initial & Last Name & Degree
Jae Hwan Lee, MD, PhD
Facility Name
Gang Neung Asan Hospital
City
Gangneung
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sang-Sig Jeong, MD, PhD
Phone
82-2-3010-3150
Email
sscheng@gnah.co.kr
First Name & Middle Initial & Last Name & Degree
Sang-Sig Jeong, MD, PhD
Facility Name
Ulsan University Hospital
City
Ulsan
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eun-Seok Shin, Md, PhD
Phone
82-3010-3155
Email
jksong@amc.seoul.kr
First Name & Middle Initial & Last Name & Degree
Eun-Seok Shin, MD, PhD
12. IPD Sharing Statement
Citations:
PubMed Identifier
32381162
Citation
Turc G, Lee JY, Brochet E, Kim JS, Song JK, Mas JL; CLOSE and DEFENSE-PFO Trial Investigators. Atrial Septal Aneurysm, Shunt Size, and Recurrent Stroke Risk in Patients With Patent Foramen Ovale. J Am Coll Cardiol. 2020 May 12;75(18):2312-2320. doi: 10.1016/j.jacc.2020.02.068.
Results Reference
derived
PubMed Identifier
29544871
Citation
Lee PH, Song JK, Kim JS, Heo R, Lee S, Kim DH, Song JM, Kang DH, Kwon SU, Kang DW, Lee D, Kwon HS, Yun SC, Sun BJ, Park JH, Lee JH, Jeong HS, Song HJ, Kim J, Park SJ. Cryptogenic Stroke and High-Risk Patent Foramen Ovale: The DEFENSE-PFO Trial. J Am Coll Cardiol. 2018 May 22;71(20):2335-2342. doi: 10.1016/j.jacc.2018.02.046. Epub 2018 Mar 12.
Results Reference
derived
Learn more about this trial
Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale (DEFENSE-PFO)
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