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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Medical Management | Sham Comparator | 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). |
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| PFO Closure | Experimental | Will undergo Intracardiac Echo (ICE) in cardiac catheterization lab and undergo PFO device closure procedure with the AMPLATZER PFO Occluder. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sham Procedure | Other | 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. |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Beck Depression Inventory (BDI) Scale | 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. | 12 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sherman Sorensen, M.D. | Intermountain Health Care, Inc. | 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 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Joseph's Hospital & Medical Center | Phoenix | Arizona | 85013 | United States | ||
| UCLA School of Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29191325 | Derived | 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. |
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60 day baseline diary completion prior to randomization.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sham Procedure | Did not receive the closure device, and treated with the current standard of care medical treatment. |
| FG001 | Patent Foramen Ovale (PFO) Device Closure | Patent foramen ovale (PFO) device Closure procedure using the AMPLATZER PFO Occluder device. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Randomization Period |
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| AMPLATZER PFO Occluder | Device | Patients in this arm will receive the AMPLATZER PFO Occluder device |
|
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 |
| Los Angeles |
| California |
| 90095 |
| United States |
| Memorial Hospital | Colorado Springs | Colorado | 80909 | United States |
| Swedish Medical Center | Englewood | Colorado | 80113 | United States |
| Medical Center of the Rockies | Fort Collins | Colorado | 80528 | United States |
| Washington Hospital Center | Washington D.C. | District of Columbia | 20010 | United States |
| University of Iowa | Iowa City | Iowa | 52240 | United States |
| University of Kentucky | Lexington | Kentucky | 40536 | United States |
| Ochsner Clinic Foundation | New Orleans | Louisiana | 70124 | United States |
| Tufts Medical Center | Boston | Massachusetts | 02111 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| William Beaumont Hospital | Royal Oak | Michigan | 48073 | United States |
| Abbott Northwestern Hospital | Minneapolis | Minnesota | 55407 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| St. Cloud Hospital | Saint Cloud | Minnesota | 56303 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| St. Johns's Mercy Medical Center | St Louis | Missouri | 63141 | United States |
| Alegent Health Bergan Mercy Medical Center | Omaha | Nebraska | 68124 | United States |
| Children's Heart Center Las Vegas | Las Vegas | Nevada | 89109 | United States |
| Mercy Hospital of Buffalo | Buffalo | New York | 14214 | United States |
| University of Rochester Medical School | Rochester | New York | 14642-8679 | United States |
| Pinnacle Health Hospitals | Harrisburg | Pennsylvania | 17104 | United States |
| Thomas Jefferson University | Philadelphia | Pennsylvania | 19107 | United States |
| The Methodist Hospital | Houston | Texas | 77030 | United States |
| St. Mark's Hospital | Salt Lake City | Utah | 84124 | United States |
| Intermountain Medical Center | Salt Lake City | Utah | 84143 | United States |
| Inova Healthcare Services | Falls Church | Virginia | 22042 | United States |
| University of Washington Medical Center | Seattle | Washington | 98195 | United States |
| St. Luke's Medical Center | Milwaukee | Wisconsin | 53215 | United States |
| Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| COMPLETED |
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| NOT COMPLETED |
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| Optional Patent Foramen Ovale Closure |
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| ID | Title | Description |
|---|---|---|
| BG000 | Sham Procedure | Participants 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). |
| BG001 | PFO Device Closure | Participants will undergo Intracardiac Echo (ICE) in cardiac catheterization lab and undergo PFO device closure procedure with the AMPLATZER PFO Occluder. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| International Classification of Headache Disorders (ICH) | Participants can have more than one International Classification of Headache Disorder, which is why the sum of the three categories exceeds the overall number of baseline participants. | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Participants included in the analysis were followed for 1-year, had Clinical Event Committee (CEC) adjudicated headache diaries, had greater than or equal to 60% diary compliance during the treatment phase (10-12 months) and were not treatment failures. | Posted | Number | percentage of subjects | Baseline and months 10-12 |
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| Primary | 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. | All enrolled subjects who received the device (randomized and Optional PFO Closure group). 5 subjects were considered to have insufficient follow-up and were therefore excluded from the analysis. | Posted | Number | 99% Confidence Interval | percentage of participants | Baseline through 12 months |
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| Secondary | 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. | Posted | Mean | Standard Deviation | Migraine days per month | Baseline and months 10-12 |
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| Secondary | Percentage of Subjects With Successful PFO Closure at 12-months | Successful Closure by Core Lab Adjudicated Transcranial Doppler (TCD) Grade <= 2 | 117 device subjects completed the 12 month visit. Only 104 had TCDs that were able to be adjudicated. Of the 13 device subjects with unadjudicated TCDs, 4 did not have valsalva data and 9 did not have TCD data available for various reasons. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline and month 12 |
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| Secondary | 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. | 101 participants in the sham group and 116 subjects in the PFO device closure group had both baseline and 12-month MIDAS scores available to perform the analysis. | Posted | Mean | Standard Deviation | units on a scale | 12 months |
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| Secondary | Incidence of a 75% Reduction in Migraine Headache Attacks | Participants were included in the analysis were followed for 1-year, have CEC adjudicated headache diaries, had greater than or equal to 60% diary compliance during the treatment phase (10-12 months) and were not treatment failures. | Posted | Number | percentage of participants | 12 months |
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| Secondary | 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. | Device group subjects who were implanted with the study device and experienced no serious device or procedure-related adverse events. | Posted | Number | 95% Confidence Interval | percentage of participants | 12 months |
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| Secondary | 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. | 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. 117 device subjects completed the 12 month visit. Only 104 had TCDs that were able to be adjudicated. | Posted | Number | 95% Confidence Interval | percentage of participants | 12 months |
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| Secondary | Incidence of All Adverse Events at 12-months | Participants who experienced an adverse event at or before 12-months post-procedure | Posted | Number | participants | 12 months |
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| Secondary | Incidence of Device-related Adverse Events | Participants who experienced a device-related adverse event, as adjudicated by the Data Safety and Monitoring Board (DSMB), at or before 12-months post-procedure. | Posted | Number | 95% Confidence Interval | percentage of participants | 12 months |
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| Secondary | Incidence of a 95% Reduction in Migraine Headache Attacks | Posted | Number | percentage of participants | 12-months |
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| Other Pre-specified | Change in Beck Depression Inventory (BDI) Scale | 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. | 101 participants in the sham group and 116 subjects in the PFO device closure group had both baseline and 12-month BDI scores available to perform the analysis. | Posted | Mean | Standard Deviation | units on a scale | 12 months |
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| Post-Hoc | Responder Rate for Subjects in Whom Majority of Attacks Were With Aura | The term "majority" in "majority of migraine attacks included aura" was defined by the Neurologist (>50%) at the time of randomization based on a review of the subject's study baseline headache diary and medical history. | Posted | Number | percentage of subjects | 12 months |
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| Post-Hoc | Percentage of Subjects With Migraine With Aura Determined to Have a Complete Cessation of Migraine Attacks According to the International Headache Society (IHS) | Complete Cessation of Migraine Attacks, baseline diary compared to months 10-12 | 6 PFO Device Closure Subjects and 3 Sham Procedure Subjects with Aura do not have 12-month follow-up data available. | Posted | Number | percentage of subjects | Baseline through months 10-12 |
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All adverse events were collected from the time of signing informed consent until the 12-month follow-up visit. After the 12-month follow-up visit, serious adverse events and/or device-related events were collected until completion of study requirements.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PFO Device Closure | PFO device Closure procedure using the AMPLATZER PFO Occluder device. | 1 | 123 | 119 | 123 | ||
| EG001 | Sham Procedure | Did not receive the closure device, and treated with the current standard of care medical treatment. | 0 | 107 | 103 | 107 | ||
| EG002 | Optional PFO Closure | Subjects randomized to the sham arm and completed their 12-month follow up visit were given the option of PFO closure with the Amplatzer PFO Occluder. | 0 | 87 | 68 | 87 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Transient atrial fibrillation after device placement | Cardiac disorders |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arterial Hypertension/Hypertension | Cardiac disorders |
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| Nausea | General disorders |
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| Fatigue/Generalized Fatigue | General disorders |
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| Cough | Respiratory, thoracic and mediastinal disorders |
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| Musculoskeletal Pain | General disorders |
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| Common cold/Upper Respiratory Tract Infection | Infections and infestations |
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| Abdominal Pain | Gastrointestinal disorders |
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| Anxiety | General disorders |
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| Rash | General disorders |
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| Pain | General disorders |
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| Urinary Tract Infection | Infections and infestations |
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| Diarrhea | Gastrointestinal disorders |
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| Dizziness | General disorders |
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| Palpitations | Cardiac disorders |
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| Sinusitis | General disorders |
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| Chest Pain | General disorders |
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| Vascular Access Site Complication Pain | Vascular disorders |
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| Bruise/Purpura Simplex | General disorders |
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| Viral Syndrome | General disorders |
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| Low Back Pain | General disorders |
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| Back Pain | General disorders |
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| Vascular Access Site Complication Hematoma | Vascular disorders |
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| Vascular Access Site Complication Bruise | Vascular disorders |
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| Mid-Sternal Chest Pressure | General disorders |
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| Headache | General disorders |
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| Depression | General disorders |
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| Dyspnea | General disorders |
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| Sore Throat | General disorders |
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| Vascular Access Site Complication Bleeding | Vascular disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Global Clinical Affairs | St. Jude Medical | 818-493-3648 | aoza@sjm.com |
| ID | Term |
|---|---|
| D008881 | Migraine Disorders |
| D054092 | Foramen Ovale, Patent |
| ID | Term |
|---|---|
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006344 | Heart Septal Defects, Atrial |
| D006343 | Heart Septal Defects |
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| Male |
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| Migraine without Aura (ICH) |
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| Migraine with and without Aura |
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| Title | Denominators | Categories | ||||
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