PREMIUM Migraine Trial

Study Overview
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Brief Summary
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The Purpose of this study is to evaluate the impact of percutaneous closure of a patent foramen ovale (PFO) (a hole in the heart), using the AMPLATZER PFO Occluder, on the incidence of migraine headaches.

Detailed Description
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The objective of this study is to evaluate whether percutaneous PFO closure is effective in reducing the incidence of disabling migraine headaches in patients who are refactory to medical treatment.

Official Title
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Prospective, Randomized Investigation to Evaluate Incidence of Headache Reduction in Subjects With Migraine and PFO Using the AMPLATZER PFO Occluder to Medical Management.

Conditions
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Migraine Headaches, Patent Foramen Ovale

Intervention / Treatment
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* Other: Sham Procedure
* Device: AMPLATZER PFO Occluder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects diagnosed as having migraine headaches both with and without aura Have a Patent Foramen Ovale (PFO) A migraine history and show a refractoriness to medical treatment Willing to participate in follow-up visits Exclusion Criteria: Subjects whose primary headaches are other than migraine headaches Who overuse migraine treatments With a clinical history of stroke or Transient Ischemic Attack (TIA) With contraindication to aspirin therapy and Clopidogrel Pregnant or desire to become pregnant within the next year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Medical Management<br>Will not receive the closure device, and will be treated with the current standard of care medical treatment. Will undergo Intracardiac Echo (ICE) in cardiac catheterization lab and simulate PFO closure procedure (sham procedure). | Other: Sham Procedure<br>* Will not receive the closure device, and will be treated with the current standard of care medical treatment. Will undergo Intracardiac Echo (ICE) in cardiac catheterization lab and simulate PFO closure procedure (sham procedure). Participants completing 1 year follow-up are eligible for PFO closure with the AMPLATZER PFO Occluder.<br>|
| Experimental: PFO Closure<br>Will undergo Intracardiac Echo (ICE) in cardiac catheterization lab and undergo PFO device closure procedure with the AMPLATZER PFO Occluder. | Device: AMPLATZER PFO Occluder<br>* Patients in this arm will receive the AMPLATZER PFO Occluder device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Endpoint - Percentage of Subjects With a 50% Reduction From Baseline in the Monthly Number of Migraine Attacks at 12 Months. | A 50% reduction from the monthly number of migraine attacks during the 60-day baseline phase to the monthly number of migraine attacks during month ten through the twelfth month in the treatment phase (device group versus sham group). | Baseline and months 10-12 | 
| Primary Safety Endpoint - Device Related Serious Adverse Event (SAE) | Number of subjects who experience a device-related major adverse event (DRMAE) through 12-months of follow-up. This endpoint was analyzed using an as-treated cohort that consists of all enrolled subjects who received the device (randomized and Optional PFO Closure group) and who had follow-up sufficient to adequately assess the DRMAE rate. | Baseline through 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Migraine Days/Month | Change in the number of migraine days is calculated by the difference in the mean number of migraine days between the baseline assessment period and the treatment phase (months 10-12 post-procedure) for the respective randomization groups. | Baseline and months 10-12 | 
| Percentage of Subjects With Successful PFO Closure at 12-months | Successful Closure by Core Lab Adjudicated Transcranial Doppler (TCD) Grade <= 2 | Baseline and month 12 | 
| Change in Migraine Disability Assessment (MIDAS) Score From Baseline to 12-months | The MIDAS questionnaire measure the impact of headaches on daily living. A total score of 0-5 equals little to no disability, 6-10 equals mild disability, 11-20 equals moderate disability, and a score 21 or greater equals severe disability. The maximum possible score is 276. | 12 months | 
| Incidence of a 75% Reduction in Migraine Headache Attacks |  | 12 months | 
| Procedural Success | Procedural success is calculated by the percent of device group subjects who were implanted with the study device and experienced no serious device or procedure-related adverse events. | 12 months | 
| Long-Term Success | Percent of PFO closure group subjects who were implanted with the study device, experienced no serious device or procedure-related adverse events and have a core-lab adjudicated TCD Grade at Valsalva ≤ 2 at 1-year. | 12 months | 
| Incidence of All Adverse Events at 12-months |  | 12 months | 
| Incidence of Device-related Adverse Events |  | 12 months | 
| Incidence of a 95% Reduction in Migraine Headache Attacks |  | 12-months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, PFO, Migraine Headache, patent foramen ovale