Transcript FDA Summary CardioSEAL® STARFlex™ Septal Occlusion System with Qwik Load

FDA Summary
CardioSEAL® STARFlex™
Septal Occlusion System with
Qwik Load
NMT Medical
P000049/S3
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FDA Summary
• FDA Review Team
• Background
• Device Description
• Nonclinical Evaluation
• Clinical Evaluation
• Panel Questions
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FDA Review Team
• ODE
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Donna Buckley
John E. Stuhlmuller, M.D.
• OSB
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Gerry Gray, Ph.D.
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Background
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STARFlex™ has the same design as the
CardioSEAL® device except that a
nitinol centering spring has been added
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CardioSEAL®
• PMA approved (12/01); closure of high risk VSDs
• HDE approved (2/00); closure of PFO in patients with
recurrent cryptogenic stroke who have failed
medical therapy
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STARFlex™ Device Description
• Occluder
• Double umbrella design
• Sizes: 23mm, 28mm, and 33mm
• Device size : Stretched defect diameter ratio is 1.7-2.0 : 1
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Delivery Catheter
• Size: 10F
• Qwik Load device - used to collapse and load occluder
into the delivery catheter
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Nonclinical Evaluation
• In Vitro Testing
• Biocompatibility Testing
• In Vivo (Animal) Testing
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Clinical Evaluation
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Clinical Data Sets
• Pivotal Cohort – STARFlex™ PFO
• Non-pivotal
• CardioSEAL® (PFO)
• Clamshell I F/U (PFO)
• STARFlex™ (non-PFO)
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Pivotal Cohort - PFO
• Patient subset of High-Risk Registry
• Open-label, single arm
• No control group
• Meets criteria for “Compassionate Use”
• Primarily single-center study
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Pivotal Cohort - PFO
• 49 patients
• Devices placed in 49 of 49 patients
attempted
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Patient Outcome Assessment
• Effectiveness
• Primary: Complete Defect Closure by
Echocardiographic Assessment
• Secondary: Occurrence of Potential
Neurological Events after Device
Placement
• Safety
• Adverse Events
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PFO - Effectiveness
• Primary Efficacy determined at 6-month F/U
• 44 of 49 implanted patients
• Complete closure reported in 43 of 44 patients
evaluated
• Technical errors were reported in 9 of 49 patients
• Secondary Efficacy
• No strokes and 4 transient neurological
events were reported
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PFO - Safety
• Assessment at 1, 6, 12, and 24 months
• Characterization of adverse events
• Device related
• arm fractures
• Implantation related
• Catheterization related
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PFO - Safety
• Serious or moderately serious adverse events
in 13 of 49 patients
• Device-Related - 7
• Implantation-Related - 1
• Catheterization-Related - 5
• Arm fractures in 7 of 49 devices
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Panel Questions
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Question 1
1a. Please discuss the use of “Procedural
Success” as the primary efficacy outcome
measure for assessment of clinical benefit.
1b. Please discuss the use of the occurrence
of potential embolic neurological events
after device placement as a secondary
efficacy outcome measure for assessment
of clinical benefit.
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Question 2
2a. Please discuss the use of “Serious and Moderately
Serious Adverse Events” (that were definitely,
probably or possibly related to the device,
implantation or catheterization procedure) as the
primary safety outcome measure for assessment
of clinical benefit versus risk.
2b. Please discuss whether the echocardiographic
evaluation and clinical evaluation (definitions for
occurrence of neurological events) allow adequate
assessment of device-related clinical events.
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Question 2 (cont)
2c. Please discuss whether adequate information has
been provided to allow assessment of the risk of
recurrent cryptogenic stroke versus risk of devicerelated neurological event.
2d. Please discuss whether adequate information has
been provided to characterize the appropriate
post-device placement antiplatelet regimen
(duration and single versus combination therapy)
or anticoagulation regimen (duration and target
INR).
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Question 3
3. Please comment on the lack of a prespecified control group, pre-specified
outcome measures, and pre-specified
sample size.
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Question 4a and 4b
4a. Please clarify if additional analyses on the current
data set could be performed to provide adequate
information to support safety and effectiveness.
4b. Please clarify if the collection of additional data
using the current patient selection criteria and
outcome measures would be adequate to support
safety and effectiveness.
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Question 4c
4c. Alternatively, if you believe that a new trial is
required, please address the following clinical trial
design questions:
i. Given our current understanding of the causal
relationship of the presence of PFO and stroke
(presumed paradoxical embolism), please discuss
whether a randomized trial is necessary to evaluate
safety and effectiveness. If so,
1. Can a randomized trial be completed at this time?
2. What is an appropriate control group?
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Question 4c (cont)
ii. Please discuss whether adequate trials can be designed
with historical controls or objective performance criteria.
iii. Based on the type of study design proposed, please
address the following issues:
1. Please characterize the appropriate patient population
for study enrollment.
2. Please discuss the appropriate primary and s
secondary outcome measures for evaluation of
effectiveness and safety. As part of this discussion,
please comment on the use of clinical versus surrogate
endpoints.
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Question 4c (cont)
3. Please discuss the appropriate duration of patient
follow-up.
4. Please comment on what would be a clinically
relevant sample size.
5. Please discuss the criteria for a successful trial.
6. Please comment on whether adjunctive
antithrombotic medication regimens should be left
to the operator or prospectively outlined in the
protocol.
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Question 5
5.
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Please discuss any improvements that could be
made to the training program.
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Question 6
6a. Please comment on the
INDICATIONS FOR USE section as to
whether it identifies the appropriate
patient populations for treatment with
this device.
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Question 6 (cont)
6b. Please comment on the
CONTRAINDICATIONS section as to
whether there are conditions under
which the device should not be used
because the risk of use clearly
outweighs any possible benefit.
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Question 6 (cont)
6c. Please comment on the
WARNING/PRECAUTIONS section
as to whether it adequately
describes how the device should
be used to maximize benefits and
minimize adverse events.
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Question 6 (cont)
6d. Please comment on the
OPERATOR’S INSTRUCTIONS as to
whether it adequately describes how
the device should be used to
maximize benefits and minimize
adverse events.
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Question 6 (cont)
6e. Please comment on the
remainder of the device labeling
as to whether it adequately
describe how the device should
be used to maximize benefits and
minimize adverse events.
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Question 7
7. Based on the clinical data provided in the Panel
Package, do you believe that additional follow-up
data or post market studies are necessary to
evaluate the chronic effects of the implantation
of the STARFlex™ device. If so, how long
should patients be followed and what endpoints
and adverse events should be measured?
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