GORE® Septal Occluder Device for Patent Foramen Ovale (PFO) Closure in Stroke Patients (REDUCE)

GORE® HELEX® Septal Occluder / GORE® CARDIOFORM Septal Occluder and Antiplatelet Medical Management for Reduction of Recurrent Stroke or Imaging-Confirmed TIA in Patients With Patent Foramen Ovale (PFO) - The Gore REDUCE Clinical Study

The primary objective is to determine if patent foramen ovale (PFO) closure with the GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder plus antiplatelet medical management is safe and effective and reduces the risk of recurrent stroke or imaging-confirmed transient ischemic attack (TIA) when compared to antiplatelet medical management alone in patients with a PFO and history of cryptogenic stroke or imaging-confirmed TIA.

A co-primary objective is to demonstrate that medical management plus closure with the study device reduces the risk of new brain infarct compared to medical management alone.

Study Overview

• Status: Completed
• Conditions: Stroke; Transient Ischemic Attack
• Intervention / Treatment: Drug: Antiplatelet Medical Therapy; Device: Septal Occluder Device

• Study Type: Interventional
• Enrollment (Actual): 664
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Presence of cryptogenic ischemic stroke or TIA of presumed embolic infarction verified by a neurologist within 180 days prior to randomization
• Presence of Patent Foramen Ovale (PFO), as determined initially by positive bubble study utilizing transesophageal echocardiography (TEE), demonstrating spontaneous right-to-left shunting or right-to-left shunting during Valsalva maneuver.
• Absence of an identifiable source of thromboembolism in the systemic circulation
• No evidence of a hypercoagulable state
• Note: Additional Inclusion Criteria may apply

Exclusion Criteria:

• Other co-morbidities including, but not limited to, mural thrombus, dilated cardiomyopathy, atrial fibrillation/flutter, cardiac prosthetics (valves), mitral valve stenosis, aortic dissection, significant atherosclerosis, vasculitis, pre-existing neurologic disorders, multiple sclerosis, arteriovenous malformations, prior intracranial hemorrhage, severe central nervous system (CNS) disease, severe disability related to prior stroke, and autoimmune disorders that would increase the risk of mortality or morbidity above what is typical for the treatment
• Previous Myocardial Infarction
• Active infection that cannot be treated successfully prior to randomization
• Sensitivity or contraindication to all proposed medical treatments
• Pregnancy or intent on becoming pregnant through 24-months after randomization
• Indications outside the parameters accepted for placement of the GORE® HELEX® Septal Occluder / GORE® Septal Occluder, including extensive congenital cardiac anomalies and defect diameter estimated to be > 18mm
• Atrial septal anatomy that is expected to necessitate placement of more than one GORE® HELEX® Septal Occluder / GORE® CARDIOFORM Septal Occluder
• Need for concomitant procedure(s) that may confound detection of adverse events related to device placement
• Note: Additional Exclusion Criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Medical Management; Antiplatelet medical therapy alone	Drug: Antiplatelet Medical Therapy; Investigator's choice of one of three regimen options specified in protocol; Other Names: Plavix; Aspirin; Clopidogrel; Aggrenox; Dipyridamole
Experimental: Device Closure; PFO closure with study septal occluder device plus antiplatelet medical therapy	Drug: Antiplatelet Medical Therapy; Investigator's choice of one of three regimen options specified in protocol; Other Names: Plavix; Aspirin; Clopidogrel; Aggrenox; Dipyridamole; Device: Septal Occluder Device; PFO closure with study septal occluder device; Other Names: GORE® HELEX® Septal Occluder; GORE® CARDIOFORM Septal Occluder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Freedom From Recurrent Ischemic Stroke (Primary Outcome #1)	A recurrent stroke event was defined as the first occurrence post-randomization of either a) neurological deficit presumed due to ischemia and persisting longer than 24 hours or until death, or b) transient neurological deficit presumed due to ischemia, persisting less than 24 hours with MRI evidence of a new relevant brain infarction.	24 months
Number of Subjects With New Brain Infarct or Recurrent Stroke (Primary Outcome #2)	Responders were subjects who showed one or more new infarctions on MRI since screening, or experienced a confirmed recurrent stroke, through 24 months (913 days). Nonresponders were subjects who did not show new infarction on MRI since screening and were confirmed free of recurrent stroke through at least 549 days. An infarction was defined as a new (since screening) T2 hyperintense MRI lesion with diameter ≥ 3 mm.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Study-related Serious Adverse Events	Adverse event seriousness and relationship to study treatments (device, procedure, or antiplatelet medical therapy) as reported by each investigative site	24 months
Number of Subjects With Effective Closure in Test (Device) Arm	Assessment of PFO closure in test (device) arm subjects by transesophageal echocardiography (TEE) at 24-month follow-up. Effective closure defined as occluded, small, or moderate shunt (0-25 bubbles).	24 months

Collaborators and Investigators

• Sponsor: W.L.Gore & Associates
• Investigators: Principal Investigator: Scott E. Kasner, MD, FAHA, University of Pennsylvania Medical Center; Principal Investigator: John F. Rhodes, MD, Medical University of South Carolina; Principal Investigator: Lars Søndergaard, MD, Rigshospitalet, Denmark

Publications and helpful links

General Publications

• Messe SR, Erus G, Bilello M, Davatzikos C, Andersen G, Iversen HK, Roine RO, Sjostrand C, Rhodes JF, Sondergaard L, Kasner SE; Gore REDUCE Study Investigators. Patent Foramen Ovale Closure Decreases the Incidence but Not the Size of New Brain Infarction on Magnetic Resonance Imaging: An Analysis of the REDUCE Trial. Stroke. 2021 Nov;52(11):3419-3426. doi: 10.1161/STROKEAHA.121.034451. Epub 2021 Aug 30.
• Kasner SE, Thomassen L, Sondergaard L, Rhodes JF, Larsen CC, Jacobson J. Patent foramen ovale closure with GORE HELEX or CARDIOFORM Septal Occluder vs. antiplatelet therapy for reduction of recurrent stroke or new brain infarct in patients with prior cryptogenic stroke: Design of the randomized Gore REDUCE Clinical Study. Int J Stroke. 2017 Dec;12(9):998-1004. doi: 10.1177/1747493017701152. Epub 2017 Mar 24.
• Sondergaard L, Kasner SE, Rhodes JF, Andersen G, Iversen HK, Nielsen-Kudsk JE, Settergren M, Sjostrand C, Roine RO, Hildick-Smith D, Spence JD, Thomassen L; Gore REDUCE Clinical Study Investigators. Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke. N Engl J Med. 2017 Sep 14;377(11):1033-1042. doi: 10.1056/NEJMoa1707404. Erratum In: N Engl J Med. 2020 Mar 5;382(10):978.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2008
• Primary Completion (Actual): April 24, 2017
• Study Completion (Actual): May 11, 2020

Study Registration Dates

• First Submitted: August 19, 2008
• First Submitted That Met QC Criteria: August 20, 2008
• First Posted (Estimate): August 21, 2008

Study Record Updates

• Last Update Posted (Actual): November 20, 2020
• Last Update Submitted That Met QC Criteria: October 23, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: stroke; transient ischemic attack; TIA; PFO; Patent foramen ovale; cryptogenic; HELEX; Septal Occluder; PFO Occluder
• Additional Relevant MeSH Terms: 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; Ischemic Attack, Transient; Foramen Ovale, Patent; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Clopidogrel; Dipyridamole
• Other Study ID Numbers: HLX 06-03