Evaluation of the STARFlex® Septal Closure System in Patients With a Stroke or TIA Due to the Possible Passage of a Clot of Unknown Origin Through a Patent Foramen Ovale (PFO)

A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex® Septal Closure System Versus Best Medical Therapy in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale

The primary objective of the study is to determine whether the STARFlex® septal closure system will safely and effectively prevent a recurrent embolic stroke/transient ischemic attack (TIA) and mortality in patients with a PFO and to demonstrate superiority of the STARFlex® device compared to best medical therapy.

Study Overview

• Status: Unknown
• Conditions: Stroke; Ischemic Attack, Transient; Patent Foramen Ovale
• Intervention / Treatment: Drug: Best medical therapy; Device: STARFlex septal closure system

• Study Type: Interventional
• Enrollment (Anticipated): 900
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

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

Description

Major Inclusion Criteria:

• Age 18-60 years inclusive.
• Positive contrast valsalva bubble study by trans-esophageal echocardiogram (TEE) for patent foramen ovale (PFO), with or without atrial septal aneurysm.
• Stroke or clinically definite TIA (contact study coordinator).
• Be able to comply with follow up over two years.
• Be competent to, or have a legal guardian competent to, provide informed consent following full disclosure of risks and benefits of both treatment arms by a study investigator.
• Venous access capable of accepting a 10F minimum vascular sheath.
• Have, or be willing to, discontinue hormonal based contraceptive use prior to enrollment and for the term of the study.
• Has cardiac anatomy based on enrollment echocardiogram that will allow for placement of the implant if randomized to the implant arm.
• Note: Additional inclusion criteria may apply. Contact study coordinator or principal investigator for details.

Post-randomization - device patients only

• The size of the PFO (measured by indentation with a soft balloon) must be amenable to selection of a STARFlex device.

Major Exclusion Criteria:

• Carotid artery stenosis > 50%.
• Intracranial stenosis > 50% appropriate to symptoms.
• Complex aortic arch atheroma with high risk features for embolism
• Aortic arch, carotid or vertebral artery dissection.
• Mitral or aortic valve stenosis, vegetation, or calcification > 5 mm mitral annular calcification (MAC) thickness.
• Active pregnancy.
• Active infections (contact study coordinator).
• Active infective endocarditis or bacteremia.
• Prosthetic heart valves in any location.
• Anterior MI within 3 months of neurological event.
• Chronic atrial fibrillation
• Thrombus in, or occluded, venous access route.
• Contraindication to heparin, aspirin, clopidogrel, or warfarin, or a known medical condition that requires continuous warfarin.
• Patient enrolled in another investigation study where clinical endpoint interference may occur.
• Permanent pacemaker or inferior vena cava (IVC) filter.
• Serum creatinine > 2.0 mg/dL
• Patients with known vasculitis or neurologic disorder.
• Baseline modified Rankin score of 3 or more.
• Hypercoagulopathies requiring long-term warfarin.
• Note: Additional exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1; Best medical therapy	Drug: Best medical therapy; aspirin (325 mg daily) and/or warfarin (target INR = 2.5)
EXPERIMENTAL: 2; STARFlex arm	Device: STARFlex septal closure system; transcatheter placement of STARFlex device to close a patent foramen ovale

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Two (2) year incidence of stroke or Hard TIA	2 years
All cause mortality for the first 30 days of follow up/discharge, whichever is longer	30 days
Neurological mortality from 31 days of follow up (F/U) or longer	31 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of primary endpoint as a total and broken down by event type/treatment group in: stroke/TIA patients (pts) and DW-MR+ pts with symptoms < 24 hours	< 24 hrs
Incidence of primary endpoint in BMT group	2 years
Per treatment group, incidence of relevant/notable adverse events (AEs)	2 years
Device group: (1) Incidence of primary endpoint in pts prescribed aspirin (325 versus 81 mg) daily, (2) Incidence of relevant/notable AEs	2 years

Collaborators and Investigators

• Sponsor: NMT Medical
• Investigators: Principal Investigator: Anthony Furlan, MD, Cleveland Clinic Foundation, Cleveland, OH

Publications and helpful links

General Publications

• Elmariah S, Furlan AJ, Reisman M, Burke D, Vardi M, Wimmer NJ, Ling S, Chen X, Kent DM, Massaro J, Mauri L; CLOSURE I Investigators. Predictors of recurrent events in patients with cryptogenic stroke and patent foramen ovale within the CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale) trial. JACC Cardiovasc Interv. 2014 Aug;7(8):913-20. doi: 10.1016/j.jcin.2014.01.170.
• Furlan AJ, Reisman M, Massaro J, Mauri L, Adams H, Albers GW, Felberg R, Herrmann H, Kar S, Landzberg M, Raizner A, Wechsler L; CLOSURE I Investigators. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med. 2012 Mar 15;366(11):991-9. doi: 10.1056/NEJMoa1009639.
• Furlan AJ, Reisman M, Massaro J, Mauri L, Adams H, Albers GW, Felberg R, Herrmann H, Kar S, Landzberg M, Raizner A, Wechsler L; CLOSURE I Investigators. Study design of the CLOSURE I Trial: a prospective, multicenter, randomized, controlled trial to evaluate the safety and efficacy of the STARFlex septal closure system versus best medical therapy in patients with stroke or transient ischemic attack due to presumed paradoxical embolism through a patent foramen ovale. Stroke. 2010 Dec;41(12):2872-83. doi: 10.1161/STROKEAHA.110.593376. Epub 2010 Nov 4.

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Study Completion (ANTICIPATED): April 1, 2010

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (ESTIMATE): September 20, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): December 30, 2008
• Last Update Submitted That Met QC Criteria: December 29, 2008
• Last Verified: November 1, 2008

More Information

Terms related to this study

• Keywords: Stroke; Patent Foramen Ovale; Cerebrovascular Accident; Transient Ischemic Attack; Heart Septal Defects, Atrial; STARFlex; CLOSURE I; Septal Closure System
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Congenital Abnormalities; Brain Ischemia; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Septal Defects, Atrial; Heart Septal Defects; Stroke; Ischemia; Ischemic Attack, Transient; Foramen Ovale, Patent
• Other Study ID Numbers: G980031; CLOSURE I