International Multicenter Patent foRamen OVale & strokE (IMPROVE) Registry (IMPROVE)

Patent foramen ovale (PFO) is a prevalent cause of ischemic stroke and transient ischemic attack (TIA) in young patients. Its role as a cause of cerebrovascular events in the older population is more controversial because of other competing causes are more frequent in the elderly. Recent randomized controlled trials (RCTs) have shown that PFO closure is associated with a 59% relative risk reduction in the risk of recurrent ischemic stroke. As such, the number of PFO closure procedures are expected to increase substantially in the upcoming years. Real world data (RWD) informing on the medical management, the risk of stroke recurrence, incident atrial fibrillation, and other outcomes in stroke patients with PFO, with and without PFO closure, will become crucial for understanding how results from RCTs are translated into clinical practice globally.

The IMPROVE (International Multicenter Patent foRamen OVale & strokE) Registry is an observational, multicenter, international registry of men and women with an ischemic stroke or TIA. The aim is to enroll 8,800 patient-years at ≥50 sites in ≥20 countries.

The IMPROVE Registry will provide important information about the management and related outcomes of patients with ischemic stroke or TIA and PFO throughout different regions of the world and across a wide spectrum of healthcare systems.

Study Overview

• Status: Active, not recruiting
• Conditions: Stroke; Atrial Fibrillation; Patent Foramen Ovale; Atrial Flutter
• Intervention / Treatment: Device: PFO closure

• Study Type: Observational
• Enrollment (Actual): 3730

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Heart & Brain Lab, Western University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The IMPROVE registry aims to include patients from Asia, Europe, Oceania, North America and Latin America. Academic, non-academic, urban and rural sites will be included. Principal investigators will be neurologists, since a confirmed diagnosis of ischemic stroke or TIA is mandatory before enrolment.

Description

INCLUSION CRITERIA (all of the following criteria should be fulfilled)

• Age ≥18 years

• Ischemic stroke or TIA within 5 years and 1 year before inclusion in the registry. Patients with cerebrovascular events occurred within one year before the inclusion in the registry should be part of the prospective cohort.

  • Ischemic stroke is defined as:

    • focal neurological deficit of central origin lasting ≥24 hours -except for death within 24hrs- with or without imaging confirmation of cerebral infarction; or
    • focal neurological deficit of central origin lasting <24 hours with corresponding imaging evidence of cerebral infarction; or
    • focal neurological deficit of central origin lasting <24 hours in patients receiving IV thrombolysis or endovascular thrombectomy with or without imaging confirmation of cerebral infarction; or
    • non-focal encephalopathy lasting more than 24 hours -except for death within 24hrs- with imaging evidence of cerebral infarction; or
    • acute and permanent retinal ischemia of arterial origin.

  • TIA is defined as:

    • focal neurological deficit of central origin lasting <24 hours without corresponding imaging evidence of cerebral infarction in patients not receiving IV thrombolysis or endovascular thrombectomy.
• Confirmed patent foramen ovale.

EXCLUSION CRITERIA:

Exclusion Criteria

• Age <18 years
• Venous stroke
• Stroke mimics
• Patients with incomplete data at 12 months after the index ischemic stroke or TIA.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sex; Female and male patients	Device: PFO closure; PFO closure after stroke or transient ischemic attack
Age >60 years of age; Patients younger or oder than 6o years of age	Device: PFO closure; PFO closure after stroke or transient ischemic attack
World region; Patients from different world regions: North America, Europe, Asia, Latin America	Device: PFO closure; PFO closure after stroke or transient ischemic attack
Stroke vs. TIA; Index event: stroke vs. TIA	Device: PFO closure; PFO closure after stroke or transient ischemic attack
Neurocardiology Teams; Patients assessed by a neurocardiology team	Device: PFO closure; PFO closure after stroke or transient ischemic attack

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent stroke	Recurrent hemorrhagic or ischemic stroke	Duration of follow-up (minimum of 3 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incident atrial fibrillation	New diagnosis of atrial fibrillation after the index date	Duration of follow-up (minimum of 3 months)
Proportion of patients undergoing PFO closure	Proportion of patients undergoing PFO closure	Within 12 months of the index diagnosis of PFO after the stroke or transient ischemic attack

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent stroke or death	Recurrent hemorrhagic or ischemic stroke, or death	Duration of follow-up (minimum of 3 months)
Recurrent stroke or myocardial infarction	Recurrent hemorrhagic or ischemic stroke, or myocardial infarction	Duration of follow-up (minimum of 3 months)

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Investigators: Principal Investigator: Luciano A Sposato, MD, MBA (PI), London Health Sciences Centre, Western University (London, ON. Canada); Principal Investigator: Antonio Arauz, MD (Co-Pi), National Institute of Neurology and Neurosurgery Manuel Velasco Suárez

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Actual): November 13, 2022
• Study Completion (Estimated): November 13, 2025

Study Registration Dates

• First Submitted: February 1, 2021
• First Submitted That Met QC Criteria: February 1, 2021
• First Posted (Actual): February 4, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• 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; Arrhythmias, Cardiac; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Septal Defects, Atrial; Heart Septal Defects; Stroke; Atrial Fibrillation; Foramen Ovale, Patent; Atrial Flutter
• Other Study ID Numbers: R-19-597

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Upon reasonable request and after the Approval of Western University Ethics Review Board

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No