PREMIUM Migraine Trial

• ClinicalTrials.gov Identifier: NCT00355056
• Recruitment Status: Completed
• First Posted: July 21, 2006
• Results First Posted: July 30, 2020
• Last Update Posted: July 30, 2020
• Sponsor: Abbott Medical Devices
• Information provided by (Responsible Party): Abbott Medical Devices

Tracking Information

• First Submitted Date: July 19, 2006
• First Posted Date: July 21, 2006
• Results First Submitted Date: May 2, 2016
• Results First Posted Date: July 30, 2020
• Last Update Posted Date: July 30, 2020
• Study Start Date: January 2006
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 14, 2020)

• Primary Efficacy Endpoint - Percentage of Subjects With a 50% Reduction From Baseline in the Monthly Number of Migraine Attacks at 12 Months. [ Time Frame: Baseline and months 10-12 ]
  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).
• Primary Safety Endpoint - Device Related Serious Adverse Event (SAE) [ Time Frame: Baseline through 12 months ]
  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.

• Original Primary Outcome Measures (submitted: July 19, 2006): Whether subjects with percutaneous PFO closure experience a reduction in migraine attacks.

Current Secondary Outcome Measures (submitted: July 14, 2020)

• Change in Mean Migraine Days/Month [ Time Frame: Baseline and months 10-12 ]
  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.
• Percentage of Subjects With Successful PFO Closure at 12-months [ Time Frame: Baseline and month 12 ]
  Successful Closure by Core Lab Adjudicated Transcranial Doppler (TCD) Grade <= 2
• Change in Migraine Disability Assessment (MIDAS) Score From Baseline to 12-months [ Time Frame: 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.
• Incidence of a 75% Reduction in Migraine Headache Attacks [ Time Frame: 12 months ]
• Procedural Success [ Time Frame: 12 months ]
  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.
• Long-Term Success [ Time Frame: 12 months ]
  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.
• Incidence of All Adverse Events at 12-months [ Time Frame: 12 months ]
• Incidence of Device-related Adverse Events [ Time Frame: 12 months ]
• Incidence of a 95% Reduction in Migraine Headache Attacks [ Time Frame: 12-months ]

• Original Secondary Outcome Measures (submitted: July 19, 2006): Change in the average number of migraine days; change in MIDAS score; reduction in the number of acute and/or rescue migraine medications; complete closure of the defect; improvement of Quality of Life; Improvement in the BECK Depression Inventory

Current Other Pre-specified Outcome Measures (submitted: July 14, 2020)

Change in Beck Depression Inventory (BDI) Scale [ Time Frame: 12 months ]

The difference in BDI between baseline and 12-months for the respective randomization groups. The highest possible score of the BDI is 63, which represents extreme depression. The lowest possible score is 0, which represents no depression.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PREMIUM Migraine Trial
• Official Title: Prospective, Randomized Investigation to Evaluate Incidence of Headache Reduction in Subjects With Migraine and PFO Using the AMPLATZER PFO Occluder to Medical Management.
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Migraine Headaches
• Patent Foramen Ovale

Intervention

• Other: Sham Procedure
  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.
• Device: AMPLATZER PFO Occluder
  Patients in this arm will receive the AMPLATZER PFO Occluder device

Study Arms

• Sham Comparator: Medical Management
  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).
  Intervention: Other: Sham Procedure
• Experimental: PFO Closure
  Will undergo Intracardiac Echo (ICE) in cardiac catheterization lab and undergo PFO device closure procedure with the AMPLATZER PFO Occluder.
  Intervention: Device: AMPLATZER PFO Occluder

• Publications *: Tobis JM, Charles A, Silberstein SD, Sorensen S, Maini B, Horwitz PA, Gurley JC. Percutaneous Closure of Patent Foramen Ovale in Patients With Migraine: The PREMIUM Trial. J Am Coll Cardiol. 2017 Dec 5;70(22):2766-2774. doi: 10.1016/j.jacc.2017.09.1105.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 28, 2010): 230
• Original Enrollment (submitted: July 19, 2006): 466
• Actual Study Completion Date: December 2015
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00355056
• Other Study ID Numbers: AGA-010
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Abbott Medical Devices
• Original Responsible Party: Not Provided
• Current Study Sponsor: Abbott Medical Devices
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Sherman Sorensen, M.D.; Intermountain Medical Center
• Principal Investigator: Stephen Silberstein, M.D.; Thomas Jefferson University
• Principal Investigator: Jonathan Tobis, M.D.; University of California, Los Angeles
• Principal Investigator: Andrew Charles, MD; University of California, Los Angeles

• PRS Account: Abbott Medical Devices
• Verification Date: July 2020