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

Phase 4

• Conditions: Patent Foramen Ovale
• Interventions: Device: Device closure; Drug: Standard medical treatment

• Registration Number: NCT01550588
• Lead Sponsor: Jae-Kwan Song

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

Study Timeline

• Study Start: 2012-02
• Study First Submitted: 2012-02-26
• Study First Submitted QC: 2012-03-07
• Study First Posted: 2012-03-12
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-28
• Last Update Posted: 2017-06-29
• Primary Completion: 2020-02
• Study Completion: 2020-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 210

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Device closure	Device closure	Amplatzer PFO occluder device
Medication	Standard medical treatment	Anticoagulation, Antiplatelet agent

Primary Outcome Measures

Name	Time	Method
Recurrence of nonfatal stroke / vascular death / TIMI-major bleeding	2-year

Secondary Outcome Measures

Name	Time	Method
Major bleeding associated with medication	2-year
Recurrent nonfatal stroke	2-year
Asymptomatic recurrent ischemic stroke on follow-up MR	2-year
Vascular death	2-year

Trial Locations

Locations (4)

Chungnam National University Hospital; 🇰🇷 Daejeon, Korea, Republic of

Gang Neung Asan Hospital; 🇰🇷 Gangneung, Korea, Republic of

Ulsan University Hospital; 🇰🇷 Ulsan, Korea, Republic of

YangSan Busan University Hospital; 🇰🇷 Busan, Korea, Republic of