Results offer compelling evidence for closure with the AMPLATZER PFO Occluder over conventional medical management alone

ST. PAUL, Minn. -- St. Jude Medical, Inc., a medical device company, today announced results from its RESPECT trial, which studied the AMPLATZER^TM PFO Occluder in the prevention of recurrent cryptogenic stroke. Evidence presented at a late breaking trial session during the 24^th Annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, sponsored by the Cardiovascular Research Foundation, shows that the primary analysis was not statistically significant but trended towards superiority, while additional analyses demonstrated superiority. Stroke risk reduction was observed across the totality of analyses with rates ranging from 46.6 percent - 72.7 percent.

According to the World Health Organization (WHO), an estimated 15 million strokes occur worldwide each year. In 2010, stroke cost the U.S. an estimated $53.9 billion in health care services, medications and missed days of work. Approximately 87 percent of all strokes are ischemic, which occur when blood clots block the blood vessels to the brain. Up to 40 percent of ischemic strokes are classified as cryptogenic, a stroke of unknown cause, and the prevalence of PFO is up to three times greater in this population.

Normal in a developing fetus, the foramen ovale allows oxygenated blood from the placenta to bypass the lungs. This small, flap-like opening typically closes shortly after birth. When this flap remains open, or patent, it is referred to as a PFO. A PFO can potentially allow dangerous clots to pass from the right side of the heart to the left, travel up to the brain and cause a stroke.

"The patient population affected by cryptogenic stroke tends to be relatively young and healthy. PFO closure with the AMPLATZER PFO Occluder is potentially a novel prevention strategy that may be superior to medications alone," said Dr. John D. Carroll, director of the Cardiac and Vascular Center and Interventional Cardiology at the University of Colorado, who presented the data at TCT. "Stroke is a devastating disease and we now have compelling evidence that shows a 46 to 72 percent risk reduction in recurrent strokes, which is meaningful for this otherwise healthy patient population with a long life expectancy."

A prospective, randomized (1:1) event driven study, the RESPECT trial began in 2003 and enrolled 980 patients at 69 centers across the U.S. and Canada. All patients in the study suffered a stroke, confirmed by MRI imaging, which was ruled cryptogenic prior to participating in the trial. 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. Enrollment was stopped once 25 primary events (stroke and all-cause mortality) occurred. All patients were monitored at one month, six months, 12 months, 18 months, 24 months and annually thereafter. Patients enrolled in the trial will continue to be followed until a regulatory decision is made by the U.S. Food and Drug Administration (FDA).

"More than a third of these patients are likely to have another stroke over their lifetime. If we can cut that number in half, we’re making a significant difference in the lives of patients and their families," said Dr. Jeffrey L. Saver, director of Stroke Center at UCLA and Professor of Neurology at David Geffen School of Medicine. "The totality of results from the RESPECT trial provides evidence that device therapy has clinically meaningful benefits for patients with a PFO and cryptogenic stroke who are at risk for recurrent stroke."

The RESPECT trial’s unique design assumed that both randomization and patient follow-up would be equal between the two arms for the duration of the study. During the trial, a difference in lost to follow-up between the two arms was observed and therefore, the raw count analysis (the intended primary endpoint analysis) was unduly biased. As a result, AGA Medical (now St. Jude Medical) disclosed to the FDA this unequal bias while still blinded to the primary endpoint data and reiterated that final analysis would include three additional, protocol-specified analyses.

The protocol-specified analyses performed on the data included the raw count analysis and three Kaplan Meier (time-to-event) analyses, the results of which are summarized below.

Intent-to-Treat (ITT) – Raw Count analyses 

Patients were counted to the arm they were randomized to, regardless of receiving treatment. This assumes a similar study population was maintained in each arm, but because the populations are different, this analysis is no longer valid.

46.6 percent risk reduction of stroke in favor of device (p = 0.131)

Intent-to-Treat – Kaplan Meier (KM) analyses

A KM analysis adjusts for any drop out differential between study arms to more accurately compare the two outcomes over time. Patients were included based on the arm they were randomized to, regardless of receiving treatment.

50.8 percent risk reduction of stroke in favor of device (p = 0.089)

Per Protocol (PP) analyses

Patients were analyzed according to whether the study treatment protocol was followed, e.g. inclusion / exclusion criteria, medical management protocol, etc.

63.4 percent risk reduction of stroke in favor of device (p = 0.034)

As Treated (AT) analyses

Patients were analyzed as to whether they actually received the treatment, e.g. device vs. medical therapy only.

72.7 percent risk reduction of stroke in favor of device (p = 0.007)

"We are pleased with the results of the RESPECT trial and remain confident in the safety and performance of the AMPLATZER PFO Occluder and the strength of our clinical trial design," said Frank J. Callaghan, president of the St. Jude Medical Cardiovascular and Ablation Technologies Division. "St. Jude Medical is committed to providing the clinical research needed to help physicians improve care for their patients."

Source: St. Jude Medical, Inc.