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

Patent Foramen Ovale Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01550588
• Other study ID #: 2011-0553
• Status: Recruiting
• Phase: Phase 4
• First received: February 26, 2012
• Last updated: June 28, 2017
• Start date: February 2012
• Est. completion date: February 2020

Study information

• Verified date: June 2017
• Source: Asan Medical Center
• Contact: Jae-Kwan Song, MD, PhD
• Phone: (82-2)-3010-3155
• Email: jksong[@]amc.seoul.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: February 2020
• Est. primary completion date: February 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Foramen Ovale, Patent
• Patent Foramen Ovale

Intervention

Device:
• Device closure
PFO Amplatzer device closure

Drug:
• Standard medical treatment
Standard Medical management using anti-coagulant therapy

Locations

Country	Name	City	State
Korea, Republic of	YangSan Busan University Hospital	Busan
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Gang Neung Asan Hospital	Gangneung
Korea, Republic of	Ulsan University Hospital	Ulsan

Sponsors (1)

Lead Sponsor	Collaborator
Jae-Kwan Song

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence of nonfatal stroke / vascular death / TIMI-major bleeding		2-year
Secondary	Recurrent nonfatal stroke		2-year
Secondary	Vascular death		2-year
Secondary	Major bleeding associated with medication		2-year
Secondary	Asymptomatic recurrent ischemic stroke on follow-up MR		2-year