Patent Foramen OvalePhase 4NCT01550588
Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale (DEFENSE-PFO)
A Phase 4 study testing Device closure and Standard medical treatment in people with Patent Foramen Ovale, run by Jae-Kwan Song at 4 sites in South Korea.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Patent Foramen Ovale
- What is being tested?
- Device closure and Standard medical treatment
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 210 participants
- Where
- 4 sitesSouth Korea
- Study dates
- Feb 2012to Feb 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
South Korea4 sites, 4 recruiting
- Recruiting
YangSan Busan University Hospital
Busan
Yong-Hyung Park, MD, PhD, 82-2-3010-3150, nadroj@chol.com
Yong-Hyun Park, MD, PhD
- Recruiting
Chungnam National University Hospital
Daejeon
Jae Hwan Lee, Md, PhD, 82-3010-3162, myheart@cnu.ac.kr
Jae Hwan Lee, MD, PhD
- Recruiting
Gang Neung Asan Hospital
Gangneung
Sang-Sig Jeong, MD, PhD, 82-2-3010-3150, sscheng@gnah.co.kr
Sang-Sig Jeong, MD, PhD
- Recruiting
Ulsan University Hospital
Ulsan
Eun-Seok Shin, Md, PhD, 82-3010-3155, jksong@amc.seoul.kr
Eun-Seok Shin, MD, PhD
About this study
Official title: Device Closure Versus Medical Therapy for Secondary Prevention in Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale : DEFENSE-PFO
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.
Read more
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.
Read the 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
- Being tested
- Device closure, Standard medical treatment
- Keywords
- PFO, Stroke
- Medical subject headings
- Foramen Ovale, Patent, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Device closureDevice
Also called PFO Amplatzer device
PFO Amplatzer device closure
Standard medical treatmentDrug
Standard Medical management using anti-coagulant therapy
| Study group | Role | What they receive |
|---|---|---|
| Medication | Placebo comparator | Anticoagulation, Antiplatelet agent Receives: Drug: Standard medical treatment |
| Device closure | Active comparator | Amplatzer PFO occluder device Receives: Device: Device closure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence of nonfatal stroke / vascular death / TIMI-major bleeding
Measured: 2-year
Secondary outcomes (4)
Recurrent nonfatal stroke
Measured: 2-year
Vascular death
Measured: 2-year
Major bleeding associated with medication
Measured: 2-year
Asymptomatic recurrent ischemic stroke on follow-up MR
Measured: 2-year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2012 (estimated)
- Study startFeb 2012
- Primary completionFeb 2020 (estimated)
- Study completionFeb 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Patent Foramen OvaleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jae-Kwan Song
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jae-Kwan Song, Asan Medical Center
- Investigators
- Jae-Kwan Song, MD, PhD, Principal investigator, Department of medicine, Asan Medical Center, University of Ulsan College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01550588
- Sponsor's protocol ID
- 2011-0553
- Status last verified
- Jun 2017
- First submitted
- 26 Feb 2012
- Last updated
- 29 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 32381162Lee 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.
PubMed 29544871
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Device Closure Versus Medical Therapy for Secondary Prevention in Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale : DEFENSE-PFO
- ClinicalTrials.gov ID
- NCT01550588
- Acronym / sponsor ID
- 2011-0553
- Conditions
- Patent Foramen Ovale
- Keywords
- PFO, Stroke
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 210 participants (estimated)
- Lead sponsor
- Jae-Kwan SongUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Feb 2020 (estimated)
- Study completion
- Feb 2020 (estimated)
- First posted
- 12 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Medication | Placebo comparator | Drug: Standard medical treatmentAnticoagulation, Antiplatelet agent |
| Device closure | Active comparator | Device: Device closureAmplatzer PFO occluder device |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (14 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Device closureAlso: PFO Amplatzer devicePFO Amplatzer device closure | Device | Device closure |
| Standard medical treatmentStandard Medical management using anti-coagulant therapy | Drug | Medication |
Primary outcome
Recurrence of nonfatal stroke / vascular death / TIMI-major bleeding
Time frame: 2-year
4 secondary outcomes
Recurrent nonfatal stroke
Time frame: 2-year
Vascular death
Time frame: 2-year
Major bleeding associated with medication
Time frame: 2-year
Asymptomatic recurrent ischemic stroke on follow-up MR
Time frame: 2-year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2017.
- Derived from this study: PubMed 32381162Turc 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.
- Derived from this study: PubMed 29544871Lee 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jae-Kwan Song, MD, PhD principal investigator
Department of medicine, Asan Medical Center, University of Ulsan College of Medicine
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Device closure and Standard medical treatment in people with Patent Foramen Ovale, run by Jae-Kwan Song at 4 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jae-Kwan Song, MD, PhD ((82-2)-3010-3155, jksong@amc.seoul.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence of nonfatal stroke / vascular death / TIMI-major bleeding (time frame: 2-year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01550588, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2017.