Stroke Data Presented From St. Jude Medical's RESPECT Trial for Patent Foramen Ovale Closure

February 8, 2013—St. Jude Medical, Inc. (St. Paul, MN) announced the presentation of additional data from its RESPECT trial at the American Stroke Association's International Stroke Conference 2013 in Honolulu, Hawaii. The RESPECT trial evaluated whether closing a patent foramen ovale (PFO) with the company's Amplatzer PFO occluder lowered the patient's risk of having another stroke.

Jeffrey L. Saver, MD, Director of the UCLA Stroke Center and Professor of Neurology at the David Geffen School of Medicine, commented on the study in the company's press release. Dr. Saver stated, “Data from the RESPECT trial indicates that patients with a device were less likely to suffer stroke, had smaller strokes, and were less likely to have the type of stroke linked to paradoxical embolism. Indications of preventing strokes on the surface of the brain and large strokes provide additional evidence of a genuine biological effect of closure with the Amplatzer PFO occluder in preventing recurrent cerebral infarcts due to a blood clot crossing through the PFO.”

As reported in Cardiac Interventions Today in October 2012, the RESPECT trial results were presented by John D. Carroll, MD, of the University of Colorado, during a late-breaking trial session at the TCT 2012: Transcatheter Cardiovascular Therapeutics conference in Miami, Florida.

According to St. Jude Medical, the purpose of analyzing these additional data from the RESPECT trial was to determine if patients in the device and medical therapy groups experienced different types of recurrent strokes and to identify the potential origin of the strokes. The results confirm that patients with a device in place were less likely to suffer another stroke and patients in the medical group experienced larger strokes. PFO closure with the Amplatzer PFO occluder demonstrated clinical evidence of risk reduction and is an important option for the prevention of recurrent stroke in carefully selected patients over conventional medical management alone, stated the company.

As summarized in the company's press release, the RESPECT clinical trial was a prospective, randomized (1:1), event-driven study designed to determine if PFO closure with the Amplatzer PFO occluder plus medical management was superior over medical management alone in the prevention of recurrent cryptogenic stroke. The study enrolled 980 patients across 69 centers in the United States and Canada. Enrollment in the trial stopped once 25 primary events occurred, all of which were recurrent, nonfatal strokes. Of the 25 strokes, nine were in patients randomized to the device group. Three of the nine strokes in the device group occurred in patients who did not have a device in place.

Before participating in the trial, all patients, ages 18–60 (average age was 46 years), experienced a stroke confirmed by magnetic resonance imaging that was ruled to be cryptogenic. Participants were randomly assigned to one of two groups. One group received the Amplatzer PFO occluder and medical management, and the other group was treated using the current medical management standard of care alone, which consists of receiving medicine to prevent clots and potentially decrease the risk of another stroke. Patients enrolled in the trial will continue to be followed until a regulatory decision is made by the US Food and Drug Administration (FDA).

The primary efficacy endpoint in the RESPECT trial was defined as a composite rate of nonfatal stroke, postrandomization (< 45 days) death, or fatal ischemic stroke. Four protocol-specified analyses were applied to the primary efficacy endpoint data to statistically test whether device treatment was superior to medical management.

The trial's original primary endpoint was a 75% reduction in the risk of recurrent ischemic stroke in the intent-to-treat population driven by a raw count distribution of stroke events between the device and medical groups. This was determined to be invalid because of a difference in the number of patients lost to follow-up in each arm of the trial. Of the three valid protocol-specified analyses, the intent-to-treat Kaplan-Meier analysis demonstrated risk reduction that did not reach statistical significance, while the other two analyses (per-protocol and as-treated) demonstrated clinically impactful and statistically significant benefits of PFO closure compared to medical management, reported St. Jude Medical.