PC-Trial: Patent Foramen Ovale and Cryptogenic Embolism

Randomized Clinical Trial Comparing the Efficacy of Percutaneous Closure of Patent Foramen Ovale (PFO) With Medical Treatment in Patients With Cryptogenic Embolism

The purpose of this study is to compare two treatments strategies to prevent further attacks in patients who have suffered an stroke or occlusion of a major artery with no obvious reason other than a persistent small opening between the upper heart chambers

Study Overview

• Status: Unknown
• Conditions: Heart Septal Defects, Atrial; Embolism, Paradoxical
• Intervention / Treatment: Drug: Medical antitrhombotic treatment; Device: Percutaneous closure of patent foramen ovale

Detailed Description

In patients who have suffered a stroke or occlusion of a large artery in another body part of unknown origin a possible cause is a small opening between the upper heart chambers (patent foramen ovale, it is called). After birth this opening closes in 75% of the population, while it persists in 25% of people. It may allow a small blood clot to pass from the veins of the legs through the heart into the brain or other parts of the body. In order to reduce the risk for a further attack we have today more therapeutic options to choose from but it is unclear which strategy have the best outcome. This study is created to compare the effect of two treatment strategies:

1. Medical treatment The purpose of medical treatment is to dilute the blood to a degree, that no thrombus formation occurs. Since the opening in the heart persists, treatment is usually recommended lifelong. And patients treated with coumadin must undergo regular blood tests to ensure an adequate effect of the drug.
2. Catheter closure of patent foramen ovale An alternative method developed to close the small opening in the heart utilizes catheters which are introduced in a blood vessel in the groin and from there advanced to the heart. An umbrella device is then delivered through the catheter, positioned within the small defect and released. The umbrella is overgrown with own tissue within weeks to months and closes the small defect for ever.

• Study Type: Interventional
• Enrollment (Actual): 414
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
    • Monash Medical Centre
  • Nedlands, Australia
    • Sir Charles Gairdner Hospital
  • Prahan, Australia
    • Alfred Hospital
• Austria
  • Vienna, Austria, 1090
    • Universitätsklinik für Innere Medizin II
• Belgium
  • Brugge, Belgium, 8000
    • A.Z. Sint-Jan AV
• Switzerland
  • Bern, Switzerland
    • University Hospital / Inselspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age below 60 years
• Ischemic stroke or peripheral thromboembolism, radiologically verified
• Absence of an identifiable cause of embolism
• Echocardiographically verified patent foramen ovale
• Sufficient recovery from index event to allow independent daily activities

Exclusion Criteria:

• Any identifiable cause for thromboembolic event other than PFO
• Cardiac diseases: mural thrombus, dilated cardiomyopathy, prosthetic heart valve or mitral stenosis, endocarditis, atrial fibrillation
• Vascular system: significant atherosclerosis or dissection of the aorta, collagen vascular disease, arteritis, vasculitis
• Pre-existing neurologic disorders or intracranial disease, e.g., multiple sclerosis, arteriovenous malformations, previous hemorrhage
• Contraindications for antithrombotic or anticoagulant therapy
• Patients already on chronic anticoagulant therapy for another disease
• Previous surgical or percutaneous PFO-closure
• Drug or alcohol abuse
• Pregnancy
• Septicemia or severe infectious disease
• Severe CNS disease
• No informed consent
• Foreseen difficulties with study compliance, especially the long-term follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Medical antitrhombotic treatment	Drug: Medical antitrhombotic treatment; Investigator's choice: Anticoagulation to INR 2.0 - 3.0 OR Aspirin 100-325 mg/d OR Clopidogrel 75-150 mg/d
Experimental: Device Implant; Percutaneous closure of patent foramen ovale	Device: Percutaneous closure of patent foramen ovale; Percutaneous implantation of an AMPLATZER® PFO Occluder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to death (Fatal stroke, cardiovascular, non-CV),	continuosly
non-fatal cerebrovascular event,	continuosly
peripheral embolism	continuosly

Secondary Outcome Measures

Outcome Measure	Time Frame
New arrhythmias,	continuosly
myocardial infarction	continuosly
rehospitalization related to PFO or its treatment	continuosly
device problems	continuosly
bleeding complications	continuosly

Collaborators and Investigators

• Sponsor: Foundation for Cardiovascular Research, Zurich
• Collaborators: Abbott Medical Devices
• Investigators: Study Chair: Bernhard Meier, MD, Dept. Cardiology, University Hospital Insel, Berne, Switzerland

Publications and helpful links

General Publications

• Meier B, Kalesan B, Mattle HP, Khattab AA, Hildick-Smith D, Dudek D, Andersen G, Ibrahim R, Schuler G, Walton AS, Wahl A, Windecker S, Juni P; PC Trial Investigators. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med. 2013 Mar 21;368(12):1083-91. doi: 10.1056/NEJMoa1211716.
• Khattab AA, Windecker S, Juni P, Hildick-Smith D, Dudek D, Andersen HR, Ibrahim R, Schuler G, Walton AS, Wahl A, Mattle HP, Meier B. Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design. Trials. 2011 Feb 28;12:56. doi: 10.1186/1745-6215-12-56.

Study record dates

Study Major Dates

• Study Start: February 1, 2000
• Primary Completion (Anticipated): February 1, 2011
• Study Completion (Anticipated): May 1, 2011

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (Estimate): September 14, 2005

Study Record Updates

• Last Update Posted (Estimate): May 27, 2009
• Last Update Submitted That Met QC Criteria: May 26, 2009
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Keywords: Paradoxical embolism, Patent foramen ovale,
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Congenital Abnormalities; Embolism and Thrombosis; Heart Defects, Congenital; Cardiovascular Abnormalities; Thromboembolism; Embolism; Heart Septal Defects; Heart Septal Defects, Atrial; Foramen Ovale, Patent; Embolism, Paradoxical
• Other Study ID Numbers: ICN98008