A Phase 3 interventional study of Prasugrel 5mg and Transcatheter Closure of Patent Foramen Ovale in Migraine Disease and Patent Foramen Ovale, sponsored by Columbia University. Recruiting at 1 site in United States. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2026-10-08.
Sponsored by Columbia University · Phase 3, Interventional, and Prevention
Migraine is a common and often disabling condition, but its exact causes are not fully understood. Some people with migraines have a small opening in the heart wall called a patent foramen ovale (PFO). In some of these patients, closing this opening or taking a medication that inhibits blood platelets (prasugrel) has been shown to reduce migraines. However, not everyone benefits, and it is unclear why. This study is being done to better understand whether closing a PFO can provide lasting migraine relief - especially in patients whose migraines improve with prasugrel.
The goal of this study is to find out whether, in patients whose migraines improve while taking prasugrel, closing the PFO along with 24 weeks of prasugrel leads to better long-term migraine relief after stopping the medication, than by taking prasugrel for 24 weeks alone.
Participants will track their migraines daily using an electronic diary, then take prasugrel and compare their migraines while on the medication. Only patients whose migraines improve on this medication will continue in the study. Eligible participants will be randomly assigned (like flipping a coin) to one of two groups: 1) Medication-only group: Continue prasugrel for 24 weeks. 2) Procedure group: Undergo a minimally invasive procedure to close the PFO and continue prasugrel for 24 weeks. After treatment, the medication will be stopped in both groups, and participants will again track their migraines for about 8 weeks.
The main question is: Do patients who have PFO closure continue to have fewer migraines after stopping prasugrel compared with those who did not have the procedure?
The hypothesis of the COMFORT-PFO Study is that a subset of migraine patients with PFO have an underlying platelet-mediated migraine mechanism in which byproducts of platelet activation or aggregation enter the cerebral circulation via the PFO at supraphysiologic levels, thereby triggering migraine.
Inhibition of platelet activity with thienopyridine therapy is expected to reduce the generation of these byproducts in the systemic venous circulation and, consequently, their passage to the cerebral circulation. Similarly, transcatheter closure of the PFO eliminates the right-to-left pathway, resulting in reduced exposure of the brain to these platelet-derived factors. In this context, a response to thienopyridine therapy may serve as a clinical marker to identify patients in whom the PFO plays a mechanistic role in migraine pathophysiology.
The primary objective of this study is to evaluate whether the clinical benefit in migraine reduction observed during initial thienopyridine therapy is maintained after treatment withdrawal, comparing subjects assigned to transcatheter PFO closure with those managed with medical therapy alone. Thienopyridine-responsiveness will be assessed using prasugrel hydrochloride in this study.
136 studies on the registry are indexed under Foramen Ovale, Patent; 47 are open to participants now.
This study's planned enrollment of 32 is below the median of 154 across 69 interventional studies indexed under Foramen Ovale, Patent.
Browse Foramen Ovale, Patent studies →Columbia University is the lead sponsor of 1,136 studies on the registry; 195 are open to participants now.
Of its 180 completed or terminated interventional studies of FDA-regulated products, 148 (82%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patient Inclusion Criteria:
Patient Exclusion Criteria:
Exclusions due to underlying patient medical issues:
Exclusion Due to Medication Restrictions:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
16 patients will be randomized to this group. Thienopyridine medication (prasugrel) which was demonstrated to reduce headache frequency during study screening phases, will be continued for 6 months and then stopped. Post-therapy headache frequency will be compared with the patient's baseline headache frequency. After completion of the study procedures, patients in this group will be given the opportunity to get the PFO closure procedure.
Drug: Prasugrel 5mg
16 patients will be randomized to this group. After demonstrating thienopyridine (prasugrel) benefit for migraine symptoms in the screening phases of the study, patients in this arm will undergo PFO closure, a non-surgical outpatient catheter procedure. They will remain on prasugrel for an additional 6 months. The medication will then be stopped. Post-therapy headache frequency will be compared with the patient's baseline headache frequency.
Drug: Prasugrel 5mg · Device: Transcatheter Closure of Patent Foramen Ovale
Six months of daily prasugrel therapy following randomization.
Also known as: Prasugrel Hydrochloride
A standard transcatheter closure of PFO will be performed in the Group B cohort. During this non-surgical procedure, the GORE Cardioform Septal Occluder will be used to close the PFO (it is FDA-approved for exactly this purpose for prevention of recurrent stroke) but will be used here in an off-label fashion.
Reduction in Monthly Migraine Days (MMD)
The primary efficacy endpoint is the proportion of randomized subjects maintaining a clinically meaningful migraine response, defined as a ≥50% reduction in Monthly Migraine Days (MMD) in the Post-Therapy monitoring session, compared with the Baseline monitoring session (following discontinuation of prasugrel).
Time frame: upon completion of the 56-day Post-Therapy monitoring session
Effect Persistence (EP)
Effect Preservation (EP) is a constructed metric which defines the extent to which the clinical benefit of migraine reduction observed during thienopyridine therapy is maintained following discontinuation of therapy. EP is calculated for each randomized subject as the proportion of the On-Therapy reduction in Monthly Migraine Days (MMD) that is preserved during the Post-Therapy period, expressed as a percentage. For each subject, EP is defined as: EP = (Post-Therapy Reduction in MMD / On-Therapy Reduction in MMD) × 100 where: Post-Therapy Reduction in MMD = Baseline MMD - Post-Therapy MMD On-Therapy Reduction in MMD = Baseline MMD - On-Therapy MMD EP provides a continuous, subject-level measure of treatment durability, allowing comparison of the extent to which the initial treatment effect is maintained following therapy discontinuation.
Time frame: upon completion of the 56-day Post-Therapy monitoring session
Responder-based Endpoints
Responder-based endpoints will assess higher thresholds of clinical response and will include the proportion of subjects achieving: * ≥75% reduction in MMD from Baseline during the Post-Therapy monitoring period * ≥90% reduction in MMD from Baseline, representing near complete elimination of migraine days * 100% reduction in MMD from Baseline, representing complete elimination of migraine days.
Time frame: upon completion of the 56-day Post-Therapy monitoring session
Absolute reduction in MMD from Baseline to Post-Therapy
This measure will calculate the absolute difference in MMD between the Baseline monitoring session and the Post-Therapy monitoring session.
Time frame: upon completion of the 56-day Post-Therapy monitoring session
Percent reduction in MMD from Baseline to Post-Therapy
This measure will assess the percentage difference in MMD between the Baseline monitoring session and the Post-Therapy session.
Time frame: upon completion of the 56-day Post-Therapy monitoring session
Change in MSQ 2.1 Score (Baseline Score - Post-thienopyridine Score)
The Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 is a 14-item patient-reported questionnaire to evaluate the impact of migraines on a patient's quality of life across 3 domains: Role Function-Restrictive (measures how migraines limit daily, social, and work-related activities), Role Function-Preventive (measures how migraines prevent these daily activities from happening altogether), and Emotional Function (assesses the emotional toll, frustration, and helplessness caused by migraines). In this modified version, the minimum score is 0, and the maximum score is 70, with each answer to the 14 questions receiving from 0 to 5 points. The cumulative score will be assessed at Baseline and after Treatment. The lower the score, the better Quality of Life. The absolute difference in the cumulative score will be compared, with a reduction from baseline indicating an improvement in quality of life.
Time frame: Baseline and upon completion of the 56-day Post-Therapy monitoring session
Change in HIT-6 Score (Baseline Score - Post-thienopyridine Score)
The HIT-6 (Headache Impact Test) is a 6-item patient-reported questionnaire that measures how severely headaches impact daily life, social functioning, and ability to concentrate. Scores range from 36 to 78, with higher numbers indicating greater headache-related disability. This measure will assess the difference from the Baseline (at enrollment) HIT-6 score, to the HIT-6 score after completion of the Post-Therapy monitoring session. A decrease in the HIT-6 score reflects a reduction of the life impact imposed by migraines.
Time frame: Baseline and upon completion of the 56-day Post-Therapy monitoring session
Plan to share: Yes — Upon completion, all study information will be de-identified, and shared with our colleagues at the Centro Cardiologico Monzino (Milan, Italy), Dr. Daniela Trabattoni. Dr. Trabattonia and her colleagues are performing a parallel trial with the same protocol, but using a PFO closure device not available in the United States.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code
Time frame: Starting April 2026, all supportive information is being shared collaboratively. No IPD will be shared until the study is completed at both sites (estimated 2028).
Access criteria: The two principal investigators (Sommer and Trabattoni) will have access to the de-identified data and supporting information, as well as their dedicated research teams. Outcome data from the two sites will be compared and potentially combined into a single report.
Start is estimated for Oct 2026; primary completion for Dec 2027, 14 months later.
Start moved once since we started tracking on Sep 25, 2026: Sep 2026 → Oct 2026, on Oct 8, 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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