COMFORT-PFO Study

A new medical trial, called the COMFORT-PFO Study, is currently enrolling migraine sufferers in the United States (with a parallel study taking place in Italy) to identify patients in whom thienopyridine therapy is associated with improvement in migraine symptoms, and to determine whether PFO closure may help maintain that improvement after the medication is stopped.

Study Background and Rationale 

• About 20–25% of all migraine sufferers have a small opening in the heart wall called a patent foramen ovale (PFO). 
• The PFO has been associated with migraine headaches for over 25 years. 
• PFO closure has been associated with improvement in migraine symptoms in some, but not in all individuals. 
• Treatment of patients with migraine and PFO using a class of platelet-inhibiting medications (thienopyridines) has also been associated with improvement in migraine symptoms. 
• Observational studies have shown a correlation between response to thienopyridine therapy and response to PFO closure. 
• A short course of thienopyridine treatment may help identify migraine patients in whom platelet-related factors passing through the PFO may contribute to migraine symptoms in some patients and may help identify those more likely to benefit from PFO closure.

About Migraine Headaches

Migraine headaches affect nearly 45 million Americans and over one billion people worldwide.

Despite how common and disabling they are, the underlying mechanisms of migraine are not well understood.

• While a large number of preventive medications are available, there is no one treatment that works for all patients, nor any reliable way to predict which medication might benefit an individual patient. 
• When an effective regimen can be identified, patients typically require long-term therapy, which may be associated with ongoing costs, medication side effects, and incomplete symptom control. 
• There remains a need for more effective and predictable preventive treatment options. 

COMFORT-PFO Study Design

• Migraine patients will be screened with an ultrasound test to determine whether they have a PFO, which is present in about 20–25% of individuals. 
• If a PFO is identified, participants will receive a thienopyridine medication (prasugrel) to evaluate whether their migraine symptoms improve. 
• If the headaches do not improve, it suggests that platelet-related factors may be less likely to play a role, and that the patient may be less likely to benefit from PFO closure. 
• If headaches do improve, the PFO may be an important contributor to migraines, and the patient will be eligible to participate in the treatment phase of the study. 
• Participants who improve on prasugrel will then be randomly assigned (by chance) to one of two treatment groups: 
  • The first group will receive prasugrel treatment for an additional 24 weeks. 
  • The second group will undergo PFO closure and also receive prasugrel for 24 weeks. 
• After 24 weeks, outcomes will be compared between the groups after discontinuation of prasugrel therapy to assess the durability of migraine improvement after discontinuation of therapy.

The COMFORT-PFO Study is designed to evaluate whether response to thienopyridine therapy can identify patients in whom PFO closure may help maintain migraine improvement after discontinuation of the medication.

What is a PFO?

A patent foramen ovale (PFO) is a small flap-like opening between the upper chambers of the heart.

• It is present in everyone before birth and usually closes shortly afterward. 
• In about 20–25% of people, it remains partially open. 
• The vast majority of people with a PFO have no symptoms and do not require any treatment. 

In some cases, a PFO has been associated with conditions such as stroke and migraine, although the exact relationship is not fully understood.

How the COMFORT-PFO Study Works

Participation in the Study involves several steps:

1. Screening
   1. Participants will undergo an ultrasound study to determine whether a PFO is present. 
   2. Blood tests will be done to make sure it is safe for the participant to take the study medication.
   3. Participants who meet study criteria will track their headache symptoms for 8 weeks to establish their baseline headache burden
2. Medication Evaluation
   1. Participants will then receive a short course of a platelet-inhibiting medication (prasugrel). 
   2. Migraine symptoms will be tracked to assess whether there is improvement while taking the medication. 
3. Eligibility for Randomization
   1. Only participants who show improvement during the medication phase will continue to the study treatment phase. 
   2. This selection criterion helps identify a group in whom the PFO is most likely to play a role in migraine symptoms. 
4. Treatment Assignment
   1. Eligible participants will be randomly assigned (by chance) to one of two groups:
      1. Medication-only group: continue medication for 24 weeks 
      2. PFO closure group: undergo PFO closure and take medication for 24 weeks 
5. Follow-Up
   1. After 24 weeks, the medication will be stopped in both groups. 
   2. Migraine symptoms will again be monitored to evaluate how well improvement is maintained. 

What is the PFO Closure Procedure?

PFO closure is a minimally invasive procedure performed using cardiac catheterization techniques:

• A small tube is inserted through a vein in the leg and guided to the heart. 
• Through that tube, a PFO closure device (GORE® CARDIOFORM Septal Occluder) is placed across the opening to seal it. 
• The procedure is not open-heart surgery, and many patients go home the same day.

As with any medical procedure, there are risks, and outcomes can vary. The procedure is approved for patients with prior stroke but is being studied in this trial for its potential role in migraine treatment.

Interested in Participating?

This study is exploring a possible link between migraine, platelet activity, and PFO.

If you are interested:

• You can complete a brief screening questionnaire.
• You do not need to know whether you have a PFO before starting the screening process.