Clinical trial NCT01550588: 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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Patent Foramen Ovale
Keywords: PFO
Stroke
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2012-03-12
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

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

Primary outcomes:
measure: Recurrence of nonfatal stroke / vascular death / TIMI-major bleeding
timeFrame: 2-year
Secondary outcomes:
measure: Recurrent nonfatal stroke
timeFrame: 2-year
measure: Vascular death
timeFrame: 2-year
measure: Major bleeding associated with medication
timeFrame: 2-year
measure: Asymptomatic recurrent ischemic stroke on follow-up MR
timeFrame: 2-year
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: YangSan Busan University Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Gangneung
country: Korea, Republic of
facility: Gang Neung Asan Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
Study officials:
affiliation: Department of medicine, Asan Medical Center, University of Ulsan College of Medicine
name: Jae-Kwan Song, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.