Study to Evaluate Efficacy of Device That Closes Patent Foramen Ovale in Treating Migraine

A new study will evaluate whether closing the patent foramen ovale (PFO) could relieve pain for migraine sufferers. The RELIEF (NCT04100135) study will determine the efficacy and safety of the GORE CARDIOFORM Septal Occluder (WL Gore & Associates), an FDA-approved, permanently implanted device.¹

The investigators anticipate the trial will include approximately 150 patients aged 18 to 55 years with documented PFO. Patients will be randomized to either the device PFO closure cohort or sham. The study’s primary end points are mean reduction in migraine headache days over 40 weeks of treatment and proportion of patients with serious adverse events (AEs) associated with the GORE CARDIOFORM Septal Occluder through 30 days post-procedure.

"No previous PFO closure migraine trial has yet included such clearly defined selection criteria designed to identify those patients expected to most likely respond to this potential, PFO-mediated mechanism," said RELIEF principal investigator Robert Sommer, MD, in a press release.¹ "Clinical experiences have suggested a platelet-based connection between migraine and PFO, and there may be a correlation between PFO closure responsiveness and thienopyridine responsiveness. PFO closure may offer a mechanical method to reduce or eliminate this trigger factor."

Findings are mixed on the efficacy of the PFO closure procedure; however, observational studies indicate it is safe and may lower migraine frequency and duration. The Septal Occluder was approved to decrease the risk of recurrent stroke and includes a minimal, nitinol wire frame covered with ePTFE. The device conforms to the adjacent, native anatomy, leading to high closure rates with rapid tissue ingrowth and no reported cardiac erosions, according to Gore. There were more than 60,000 devices sold worldwide over 11 years of clinical use, according to Gore.

Enrollment requirements include meeting International Classification of Headache Disorders–3 diagnostic criteria for migraine with or without aura, at least 1 year of migraine symptom duration, and being younger than 50 years of age at migraine onset. Patients also must have failed at least 2 preventive medications, had at least 1 migraine headache per week, and have a transthoracic echocardiography or transesophageal echocardiography find the presence of PFO.

"The RELIEF Clinical Study is another example of Gore's commitment to research with the goal of improving lives,” said Jake Goble, PhD, innovation leader, and Cardiac Business leader, Medical Products Division, Gore, said in a press release.¹ "The study incorporates the learnings from past PFO-migraine studies targeting a patient population we hypothesize may truly benefit. We are excited to reach this milestone as we continue to pursue a potentially impactful treatment option for migraine headache relief."

There have previously been 3 randomized controlled trials evaluating the GORE CARDIOFORM Septal Occluder’s efficacy and safety, as well as 1 pooled study and 8 retrospective case series. The results were included in a meta-analysis published earlier this year.

The results showed that compared with control intervention, PFO closure produced a significant decline in headache frequency (odds ratio [OR], 1.5698 [95% CI, 1.0465-2.3548; P = .0293) as well as monthly migraine attacks and monthly migraine days (OR, 0.2594; 95% CI, 0.0790-0.4398; P = .0048). A subgroup analysis of individuals who completed PFO surgery showed a migraine resolution in patients with aura (OR, 1.5856; 95% CI, 1.0665-2.3575; P = .0227).²

References
1. Gore initiates the RELIEF clinical study evaluating PFO closure for migraine headache relief. News release. W. L. Gore & Associates. November 9, 2022. Accessed November 14, 2022. https://www.prnewswire.com/news-releases/gore-initiates-the-relief-clinical-study-evaluating-pfo-closure-for-migraine-headache-relief-301671991.html
2. Zhang Y, Wang H, Liu L. Patent foramen ovale closure for treating migraine: a meta-analysis. J Interv Cardiol. Published online February 2, 2022. doi:10.1155/2022/6456272