Medical Device Daily Associate

St. Jude Medical (St. Paul, Minnesota) reported the enrollment of the first patient in its ESCAPE (Effect of Septal Closure of Atrial PFO on Events of Migraine with Premere) migraine trial, making it the first company to begin enrollment in a U.S. clinical trial to evaluate the connection between patent foramen ovales (PFOs) and migraine headaches.

The trial is a prospective, randomized, two-arm, double-blind multi-center trial, with the objective to determine if patients who undergo a PFO closure procedure have a decreased number of migraines over one-year follow-up as compared to those who are maintained only on drug therapy.

The trial uses the company's Premere system, acquired via its $74 million purchase of Velocimed (Maple Grove, Minnesota) last year (Medical Device Daily, April 8, 2005).

According to St. Jude, critical features of its Premere PFO closure system include flexible, low-profile anchors that conform to the septal wall; independent anchors to position for precise placement; limited surface area and prosthetic material designed to encourage rapid endothelialization and minimize the incidence of thromboembolic complications; and an adjustable tether to adapt to varying patient anatomies.

While the Premere PFO closure system is CE-marked, it is not yet labeled in Europe for the treatment of migraines.

The first patient, a Virginia woman, will be one of more than 500 patients to participate in the study, which received approval from the FDA for an investigational device exemption (IDE) in December 2005 after receiving its conditional approval for the trial back in August (MDD, Aug. 26, 2005).

While St. Jude is the first company to begin U.S. enrollment in a migraine trial, it is most definitely not the only one seeking a slice of this potentially lucrative new market.

If these devices prove to be successful, in trials they could become one of the biggest single opportunities in interventional cardiology. Currently, more than 28 million people in the U.S., about 11% of the population, suffer migraine headaches. Of that number, an estimated 2.2 million patients have a PFO with aura, and some analysts have pegged the market opportunity in the U.S. alone at nearly $3 billion.

Other competitors include what many consider to be the current market leader in this sector, NMT Medical (Boston), whose StarFlex system is being evaluated in the UK-based MIST I (Migraine Intervention with STARflex Technology) trial. That company last month reported results from that 146-patient, 16-center trial would be presented at this month's American College of Cardiology (Bethesda, Maryland) annual scientific sessions in Atlanta.

In October, the company also received FDA approval for an investigational device exemption (IDE) to initiate a 600-patient pivotal PFO/migraine clinical study, dubbed MIST II, which has yet to begin enrollment, although the company expects it to begin sometime this quarter.

Another competitor, AGA Medical (Golden Valley, Minnesota), has recently entered the fray with a conditional approval last month from the FDA for its PREMIUM (Prospective Randomized investigation to Evaluate the incidence of headache reduction in subjects with Migraine and PFO Using the Amplatzer PFO Occluder compared to Medical Management) trial.

PREMIUM, which is expected to enroll about 400 patients at up to 30 medical centers, is a prospective, randomized, two-arm, double blind multi-center trial designed to determine whether patients who undergo closure of a PFO with the company's Amplatzer device have a reduction in both the frequency and severity of migraine headaches.

Cardia (Burnsville, Minnesota), with its Intrasept device, is enrolling patients in Europe in its Patent Foramen Ovale Closure to Reduce Migraine Attacks (FORMAT) trial.

“Migraine is one of the 20 most disabling conditions that exists, according to the World Health Organization, and despite many good medications that help control the disease, millions of patients continue to suffer,“ said Neil Pugach, MD, the first ESCAPE trial enrolling physician, a neurologist with the Brighton Research Group (Virginia Beach, Virginia). “Some patients struggle with the idea of having to take daily medications to treat their migraines, so it is exciting to think that an alternative treatment might prove successful.“

“Patent foramen ovale is a common heart defect without symptoms in most people,“ said Robert Sommer, MD, Columbia Presbyterian Hospital (New York), principal cardiology investigator for the trial. “However, PFOs have been linked to stroke and decompression illness [which may accompany activities like scuba diving], and it appears that PFOs may also play a prominent role in migraine headaches. The goal of this landmark trial is to determine if closing a PFO will help in reducing migraine attacks.“

The association between PFOs and migraine headaches was first observed by physicians who treated PFOs to remedy other medical conditions such as stroke; these physicians later noticed a reduced frequency in patients' migraine headaches.

Additional informal studies have shown reduced pain – after PFO closure – for migraine patients. It is not clear why patients with a PFO would be more likely to have migraines, or why closing the PFO might decrease migraine attacks. Some physicians speculate that blood that crosses the PFO, without being filtered by the lungs, has substances that trigger migraines.

The ESCAPE trial will be conducted at 45 leading headache clinics and 15 leading interventional cardiology clinics throughout the U.S.

Both AGA and NMT also market their PFO closure systems for a stroke indication under humanitarian device exemption regulations, but both have found the regulatory path toward achieving full PMA approval rather arduous.

They also have launched trials in the PFO closure arena via IDE exemptions, but have found that enrollment in those trials – NMT's is called CLOSURE-1 and AGA's is the Randomized Evaluation of Recurrent Stroke comparing PFO Closure to Established Current Standard of Care Treatment, or RESPECT, trial – has proceeded very slowly.

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