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RESPECT TRIAL
Fact Sheet
OVERVIEW
The RESPECT Trial (Randomized Evaluation of recurrent Stroke comparing PFO
closure to Established Current standard of care Treatment) was designed to test for
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superiority of the AMPLATZER PFO device in the treatment of cryptogenic stroke
patients compared to contemporary medical management. Clinical risk reduction was
observed across the totality of analyses with rates ranging from 51 - 73 percent.
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AMPLATZER PFO OCCLUDER
The device used in the study, AMPLATZER PFO Occluder,
is a double-disc device comprised of Nitinol mesh and
polyester fabric. Inserted into the PFO to seal the
passageway between the left and right atria, or upper
chambers of the heart, the device potentially prevents a
blood clot from traveling from one side of the heart to the
other where it could pass on to the brain causing a stroke.
The safety of PFO closure was soundly demonstrated throughout the trial. No
differences were found between device treatment and medical management in the
incidence of atrial fibrillation, transient ischemic attack, major bleeding, pulmonary
embolism or cardiac thrombus. Additionally, embolizations or evidence of thrombus
formation did not occur on the device; and there were no statistically significant
differences in the incidence of serious adverse event associated with the device, the
procedure or the study.
TRIAL DESIGN
The RESPECT trial is a prospective, randomized, event driven, multicenter trial to
determine the most effective preventive treatment for patients with cryptogenic
stroke. The trial began in 2003 and enrolled 980 patients across 69 medical centers
in the U.S. and Canada. All of the patients enrolled in the study suffered a stroke,
confirmed by magnetic resonance imaging (MRI) and ruled cryptogenic prior to
participating in the trial. The average age of patients enrolled in this study was 46
years old.
Trial participants were randomly assigned to one of two groups. One group was
assigned to receive the AMPLATZER PFO Occluder in addition to standard of care
medical management*. The other group was treated using the current standard of
care alone, which consists of receiving medications to prevent clots. Patients were
monitored at one month, six months, 12 months, 18 months, 24 months and
annually thereafter. Because this was an event driven trial, enrollment was closed
once 25 primary adverse events (stroke and all-cause mortality) occurred.
TRIAL ENDPOINTS
The primary endpoint for the RESPECT clinical trial was a composite of recurrence
of nonfatal stroke, post-randomized death or fatal ischemic stroke. The study’s
secondary endpoints included: complete closure of the PFO demonstrated by a
transesophageal echocardiogram (TEE) during six month follow-up, absence of a
recurrent symptomatic, cryptogenic, nonfatal stroke or cardiovascular death, or the
absence of a transient ischemic attack (TIA).
Upon generating more than 2,500 patient years of data and approximately eight
years of patient follow-up, St. Jude Medical announced closure of enrollment in
December 2011. 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), thus
providing substantial, ongoing follow-up for this patient population.
St. Jude Medical, Inc.
Global Headquarters
One St. Jude Medical Drive
St. Paul, MN 55117
sjm.com
Media Contacts
Kristi Warner
Tel: 651-756-2085
[email protected]
RESULTS
When comparing the results from the group that received the device to those that did
not, the totality of evidence demonstrates compelling clinical benefits of PFO closure
versus medical management, and remain optimistic heading into the U.S. regulatory
approval process.
It is important to note that there are significant logistical and statistical challenges
related to the detection of a small number (25) of clinical events in nearly 1,000
randomized patients over an eight year period. While it is recognized that an Intentto-Treat primary analysis is generally regarded as the preferred method in large
randomized trials, it is noteworthy that RESPECT was able to detect a strong trend
(50.8% stroke reduction) in favor of device closure (p=0.089) under these very
challenging conditions. When the analysis is performed on the basis of compliance
to protocol (Per-Protocol), or on the basis of the treatment they actually received
(As-Treated), PFO closure was superior to medical management from both clinical
and statistical perspectives. Three of the nine strokes in the device arm occurred in
patients who while randomized for treatment, didn’t have a device. Data from
patients who actually had a device in place indicates a dramatic reduction in stroke.

The RESPECT trial provides clinical evidence of risk reduction in the prevention
of recurrent cryptogenic stroke for select patients with history of cryptogenic
stroke and PFO. The results indicate clinical benefits for closure with the
AMPLATZER PFO Occluder over conventional medical management alone.

PFO closure with the AMPLATZER PFO Occluder has a very low risk of device
or procedure-related complications.

Results of the RESPECT trial are important for the treatment of patients with
history of cryptogenic stroke and PFO, many of which are young to middle age.
PROTOCOL-SPECIFIED ANALYSES
Intent-to-Treat: Raw Count
 Patients were counted in the arm to which they were randomized, regardless
of the treatment they actually received. This analysis assumes a similar study
population was maintained in each study arm. Because the populations
showed significantly different drop-out rates, this analysis is invalid.
Intent-to-Treat: Kaplan-Meier
 This analysis adjusts for any drop-out differential between the study arms in
order to better compare the two outcomes over time. Patients were analyzed
according to the arm to which they were randomized, regardless of the
treatment they actually received.
 Results: 50.8 percent risk reduction in favor of device (p = 0.089)
Per-Protocol: Kaplan-Meier
 Patients were analyzed according to whether they followed the study
treatment to which they were randomized, and if other study criteria were
met, e.g. inclusion / exclusion criteria, compliance to medical management
drug regimen, etc.
 Results: 63.4 percent risk reduction in favor of device (p = 0.034)
As-Treated: Kaplan-Meier
 Patients were analyzed according to the treatment they actually received,
e.g. device vs. medical therapy only.
 Results: 72.7 percent risk reduction in favor of device (p = 0.007)
* Patients who received the device had a regimen to avoid clotting when the device was first
implanted. Patients were on an antiplatelet medication for one month and aspirin for six
months post-implant. After that time period, it was up to the treating physician whether they
wanted to continue the patient on medical management or stop altogether.
St. Jude Medical, Inc.
Global Headquarters
One St. Jude Medical Drive
St. Paul, MN 55117
sjm.com
Media Contacts
Kristi Warner
Tel: 651-756-2085
[email protected]