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

NCT ID: NCT01550588

Last Updated: 2017-06-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2020-02-29

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

Conditions

Patent Foramen Ovale

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Medication

Anticoagulation, Antiplatelet agent

Group Type: PLACEBO_COMPARATOR

Standard medical treatment

Intervention Type: DRUG

Standard Medical management using anti-coagulant therapy

Device closure

Amplatzer PFO occluder device

Group Type: ACTIVE_COMPARATOR

Device closure

Intervention Type: DEVICE

PFO Amplatzer device closure

Interventions

Device closure

PFO Amplatzer device closure

Intervention Type: DEVICE

Standard medical treatment

Standard Medical management using anti-coagulant therapy

Intervention Type: DRUG

Other Intervention Names

PFO Amplatzer device

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jae-Kwan Song

OTHER

Sponsor Role: lead

Responsible Party

Jae-Kwan Song

professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jae-Kwan Song, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of medicine, Asan Medical Center, University of Ulsan College of Medicine

Locations

YangSan Busan University Hospital

Busan, , South Korea

Site Status: RECRUITING

Chungnam National University Hospital

Daejeon, , South Korea

Site Status: RECRUITING

Gang Neung Asan Hospital

Gangneung, , South Korea

Site Status: RECRUITING

Ulsan University Hospital

Ulsan, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Jae-Kwan Song, MD, PhD

Role: CONTACT

jksong@amc.seoul.kr

(82-2)-3010-3155

Facility Contacts

Yong-Hyung Park, MD, PhD

Role: primary

nadroj@chol.com

82-2-3010-3150

Jae Hwan Lee, Md, PhD

Role: primary

myheart@cnu.ac.kr

82-3010-3162

Sang-Sig Jeong, MD, PhD

Role: primary

sscheng@gnah.co.kr

82-2-3010-3150

Eun-Seok Shin, Md, PhD

Role: primary

jksong@amc.seoul.kr

82-3010-3155

References

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.

Reference Type: DERIVED

PMID: 32381162 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29544871 (View on PubMed)

Other Identifiers

2011-0553

Identifier Type: -

Identifier Source: org_study_id