Cook Zenith

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(No Transcript)
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Cook Zenith AAA Endovascular Graft and the HL-B
One-Shot? Introduction SystemP020018 April 10,
2003 FDA Circulatory System Devices Panel
MeetingGaithersburg, MD
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FDA Review Summary

• Dorothy B. Abel and A. Doyle Gantt
• DCD/PVDB

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FDA Review Team

• Lead A. Doyle Gantt and Dorothy Abel
• Clinical Paul Chandeysson, M.D.
• Statistical Gary Kamer
• In Vivo Animal Studies John Karanian,
  Ph.D.
• In Vitro Graft Mechanical Testing Terry
  Woods, Ph.D.
• In Vitro Graft Corrosion Testing Stan
  Brown, D.Eng.
• In Vitro Delivery System Kachi Enyinna

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FDA Review Team, cont.

• Biocompatibility, Packaging and
  Sterilization Lisa Kennell
• Bioresearch Monitoring Rachel Solomon
• Manufacturing/QSR John Glass/Kent
  Berthold
• Patient Labeling Walter Scott, Ph.D.

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Zenith Components
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Unique Aspects of this PMA

• This device utilizes supra-renal fixation,
  whereas other approved endovascular grafts are
  implanted infra-renal.
• There are various configurations as well as
  multiple sizes in the product line (94
  components).
• The device is indicated for isolated iliac
  aneurysms (i.e., in addition to abdominal aortic
  aneurysms, with and without iliac involvement).
• There have been device integrity issues
  identified in pre-clinical and clinical
  evaluations.

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US Clinical Study

• IDE G990135
• 15 centers
• 52 patients in Phase I (roll-in patients)
• 200 standard-risk patients in Phase II
• 100 high-risk patients in Phase II
• 80 patients who met the general inclusion
  criteria for the low risk arm of the study but
  whose arterial anatomy was not suited for
  endovascular treatment were treated surgically as
  a concurrent control

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Additional Clinical Studies

• Australasian study
• 291 patients at 16 clinical centers in Australia
  and New Zealand
• 24-month follow-up for the US pivotal study
• US continued access study
• 193 standard-risk patients
• 143 high-risk patients
• 15 additional female, standard-risk patients
• 14 patients treated under the compassionate use
  and emergency use provisions

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Additional Clinical Studies, cont.

• Worldwide marketing experience
• Western Australia Registry
• 170 patients who were treated during the
  Australasian study with longer-term follow-up,
  providing some follow-up data out to 6 years
• Eurostar Registry
• 828 patients treated at 45 clinical centers in
  Europe
• ASERNIP-S (Australian Safety and Efficacy
  Register of New Interventional Procedures
  Surgical) Registry
• 515 patients in a registry conducted by the
  Australian government

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Clinical Review Synopsis

• All clarification and additional information
  requested during the review of the clinical data
  have been provided and the review process
  continues.
• The company will continue to follow patients out
  to 5 years.
• Data are not available for treatment of isolated
  iliac aneurysms, however, this indication could
  still be considered.

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Clinical Review Synopsis, cont.

• No studies have been designed to compare the
  effect of supra-renal versus infra-renal fixation
  on renal function. The data that are available
  do not demonstrate a concern.
• There is a large amount of clinical data
  available for this device.
• The clinical and statistical reviews of this PMA
  have been provided to the panel and Dr.
  Chandeysson and Mr. Kamer will present additional
  information.

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Pre-clinical Review Summary

• The review of the biocompatibility, in vivo
  animal studies, manufacturing and sterilization
  information (including packaging and shelf-life)
  have been completed and there are no outstanding
  issues regarding these parts of the PMA.
• Additional information regarding the pre-clinical
  in vitro studies for a device modification has
  been received and the review process is ongoing.

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Device Integrity

• In order to fully characterize the potential for
  problems with device integrity over time and any
  associated clinical implications, the sponsor was
  asked to clearly describe and analyze all
  available data related to device integrity.
• This included bench testing, animal data,
  clinical data and explant analyses to evaluate
  corrosion, stent fracture, barb separation,
  suture breaks and graft material wear.

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Device Integrity, cont.

• The sponsors presentations have appropriately
  described the information available to assess
  device integrity.
• The descriptions and analyses regarding device
  integrity have been provided to the panel.

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Device Integrity Summary

• There have been no clinical sequelae associated
  with corrosion, stent fracture, and single-barb
  and double-barb separations
• there is a potential for solder loss due to
  corrosion, however, the loss in solder is not
  anticipated to be greater than 50 over 10 years
  and there is a redundancy in design intended to
  provide additional protection from migration as a
  result of barb slippage due to solder loss

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Device Integrity Summary, cont.

• stents are not expected to fracture under normal
  conditions, when the device is used in accordance
  with the IFU
• barb separations are an anticipated event for
  this device, however, the barb design is
  considered by the sponsor to be adequate under
  normal clinical conditions and there is a
  redundancy in design intended to provide
  additional protection from migration as a result
  of barb separation

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Device Integrity Summary, cont.

• suture breaks resulting in suprarenal stent
  detachment have been reported in 5 cases
  world-wide and the device has been modified in an
  attempt to address this issue
• graft material wear has not been observed to be a
  clinical problem
• appropriate patient selection may reduce the risk
  of device integrity problems and

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Device Integrity Summary, cont.

• periodic imaging follow-up is necessary for
  identification of device integrity issues and any
  potentially associated complications to allow for
  timely intervention to avoid serious clinical
  sequelae.

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Design Changes

• Flexibility in the bifurcated region had been
  increased to reduce the likelihood of stent
  fracture
• the number, positioning and method of attachment
  to the stent of the barbs on the suprarenal stent
  have been modified to reduce the likelihood of
  migration
• stents are now attached to the outside of the
  graft instead of the inside to reduce graft wear
  and to make a smooth inner lumen and

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Design Changes, cont.

• the number of sutures holding the components of
  the device together have been increased to
  minimize the potential for separation of the
  suprarenal stent.

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Device Integrity Review Synopsis

• There is extensive clinical information available
  for the Zenith Endovascular Graft.
• The reports of device integrity observations are
  complete.
• Although some devices will have integrity
  problems after implantation, adequate information
  has been provided to define the risk and to allow
  for a determination regarding safety and
  effectiveness.

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Conclusions

• All FDA requests for additional information have
  been satisfied.
• The issues identified by the review team as
  warranting discussion are outlined in the
  questions for the panel.