SUMMARY OF SAFETY AND EFFECTIVENESS DATA
`
`I.
`
`GENERAL INFORMATION
`
`Device Generic Name:
`
`Coronary Stent System
`
`Device Trade Name:
`
`DriverTM Over-The-Wire, Rapid Exchange and Multi-
`Exchange Coronary Stent System
`
`6%-
`
`Applicant's Name and Address:
`
`Medtronic Vascular
`3576 Unocal Place
`Santa Rosa, CA 95403
`USA
`
`Date(s) of Panel Recommendation: None
`
`Premarket Approval Application (PMA) Number: PO30009
`
`Date of Notice of Approval to Applicant:
`
`October 1,2003
`
`11.
`
`INDICATIONS FOR USE
`
`The Medtronic DriverTM Over-The-Wire, Rapid Exchange, and Multi-Exchange Coronary
`Stent Systems (hereinafter called the DriverTM Coronary Stent System) are indicated for
`improving coronary luminal diameter in patients with symptomatic ischemic heart disease
`due to discrete de novo or restenotic lesions with reference vessel diameters of 3.0 - 4.0
`mm and 5 30 mm in length using direct stenting or pre-dilatation. Outcome beyond 270
`days for thispermanent implant is unknown at present.
`
`>
`
`111. DEVICE DESCRIPTION
`
`The Medtronic DriverTM Coronary Stent System is comprised of two components: the
`Stent and the Delivery System. The DriverTM stent is identical despite which delivery
`system it is mounted on.
`
`The DriverTM stent consists of a series of 1 .O mm segments that are constructed from a
`continuous toroid ring manufactured from a Co-Ni-Cr-Mo alloy conforming to ASTM F
`562-00. The ring is formed into alternating upper and lower crowns with 10 radiused
`crowns per end connected by axial struts for a total of 20 crowns and 20 axial struts in a
`zigzag pattern.
`
`Page 1
`
`Medtronic Exhibit 1823
`
`

`

`The use of a new alloy facilitates the implementation of thinner struts without affecting
`the radial strength or radiopacity of the stent. Unlike 3 16L stainless steel, the new alloy
`does not contain significant levels of iron (1 .O percent by weight maximum), thereby
`enhancing MRI compatibility. In addition, the radiopacity of the Co-Ni-Cr-Mo alloy is
`greater than that of 3 16L stainless steel, due primarily to increased levels of molybdenum.
`As such, the radiopacity of 3 16L stainless steel stents is maintained with the Co-Ni-Cr-
`Mo alloy stents even with thinner stent struts
`
`The stent is mounted on one of three delivery systems. Each delivery system provides a
`means for delivering the stent through the coronary vasculature and, once in the desired
`location, expands the stent through balloon inflation. The three delivery systems
`available with the DriverTM stent are the Over-The-Wire (OTW), Rapid Exchange (RX)
`and Multi Exchange (MX) Delivery System.
`
`All delivery systems have a minimal amount of working length extending beyond the
`stent on each side. The inner lumen of the catheter is designed to accommodate a
`maximum guidewire diameter of 0.0 14 inches.
`
`Table 1 provides the product labeling specifications for the Medtronic DriverTM Coronary
`Stent and the three Delivery Systems
`
`Table 1: Product Labeling Specifications for the Medtronic DriverTM Coronary
`S tent Svs terns
`
`Nominal
`Pressure
`(atm)
`
`Rated
`Burst
`Pressure
`(atm)
`
`Medtronic DriverTM
`Over-the- Wire
`Coronary StenGystem
`
`Over-the-
`Wire
`
`Medtronic DriverTM
`Rapid Exchange
`Coronary Stent System
`
`Rapid
`Exchange
`
`Medtronic DriverTM
`Multi-Exchange MX
`Coronary Stent System
`
`Multi-
`Exchange
`
`3.0
`3.5
`4.0
`
`3 .O
`3.5
`4.0
`
`3.0
`3.5
`4.0
`
`Inner
`Diameter
`(inches)
`.056
`
`.056
`
`.064
`
`9
`12
`15
`18
`24
`30
`9
`12
`15
`18
`24
`30
`9
`12
`15
`18
`24
`30
`
`9
`
`16
`
`16
`
`16
`
`Page 2
`
`Medtronic Exhibit 1823
`
`

`

`IV.
`
`CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS
`
`Contraindications
`
`The Driver Coronary Stent System is contraindicated for use in:
`Patients in whom antiplatelet and/or anticoagulation therapy is
`contraindicated.
`Patients who are judged to have a lesion that prevents complete inflation of
`an angioplasty balloon.
`
`k
`
`Warnings and Precautions
`
`A list of warnings and precautions can be found in the device labeling.
`
`V.
`
`ALTERNATIVE PRACTICES AND PROCEDURES
`
`Patients with early coronary artery disease receive exercise, diet, and drug therapy as
`appropriate. If the disease progresses, alternative practices specific to the treatment of
`coronary artery disease include: percutaneous transluminal coronary angioplasty (PTCA),
`drug therapy (e.g., thrombolytic agents, antiplatelet agents, and anticoagulant agents),
`Coronary Artery Bypass Graft Surgery (CABG), and stenting with other commercially
`available stents.
`
`VI. MARKETING HISTORY
`
`The Driver Coronary Stent System has been approved for commercial distribution in the
`European Union, Canada, China, Australia and Singapore. The Driver Coronary Stent
`System has not been withdrawn from marketing for any reason relating to the safety and
`effectivenesuf the device.
`
`*
`
`VII. SUMMARY OF PRECLINICAL STUDIES
`
`Biocompatibility
`
`All biocompatibility testing was performed in accordance with;
`
`0
`
`Guidance for the Submission of Research and Marketing Applications for
`Interventional Cardiology Devices; published by the Interventional Cardiology Devices
`Branch, Division of Cardiovascular, Respiratory and Neurology Devices, Office of
`Device Evaluation in May 1995.
`
`0
`
`IS0 10993, Biological Evaluation of Medical Devices
`
`Page 3
`
`Medtronic Exhibit 1823
`
`

`

`The following biocompatibility tests were conducted and passed on the DriverTM
`Coronary Stent System:
`
`Biocompa
`Component
`Stent Raw
`Material
`
`d i t y Testing on (
`Biological Effect
`Cytotoxicity
`
`Sensitization
`
`k
`
`Irritation
`
`Systemic Toxicity
`
`Mutagenicity /
`Genotoxicity
`
`e
`
`Implantation /
`Subchronic toxicity
`
`Hemocompatibility
`
`Skin Sensitization Kligman
`Maximization test-IS0
`
`Intracutaneous Injection
`Test-IS0
`
`System Injection test-IS0
`
`~~
`
`I-Ni-Cr-Mo alloy (DriverTM Stent)
`Test
`Criterion
`L929 MEM Elution Test-
`01-2293-GI
`IS0
`Results must indicate a
`grade of 2 or lower.
`01-2293-GI1
`No dermal inflammatory
`response greater than the
`control.
`01-2293-GS
`No greater adverse
`reactions or responses
`when compared to the
`controls.
`0 1 -2293-G9
`No greater adverse
`reactions or responses
`when compared to the
`controls.
`01-2293437
`The test article must not
`induce a significant
`increase in the number of
`micronucleated cells when
`compared to controls.
`0 1-229346
`The test article must not
`induce a significant
`increase in reversion in
`the genomes of the
`organisms tested, when
`compared to controls.
`01-2293-G5
`Test article extraEts must
`not be considered
`mutagenic when
`compared to controls.
`0052D640 P1056
`No capsule formation or
`other adverse reaction to
`the implanted test article.
`01-2293-G3
`The test article must not
`induce complement
`activation when compared
`to controls.
`
`Rodent Bone Marrow
`Micronucleus Assay-IS0
`
`Chromosomal Aberration
`Assay-IS0
`
`S. typhimurium/ E.coli
`Reverse Mutation Assay-
`IS0
`
`Biocompatibility Implant
`Study
`
`C3a Complement Activation
`Assay
`
`Results
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Page 4
`
`Medtronic Exhibit 1823
`
`

`

`Unactivated Partial
`Thromboplastin Time
`Assay-IS0
`
`~~~~
`
`In Vitro Hemocompatibility
`Assay-IS0
`
`Bc
`
`Pyrogenicity
`
`Rabbit Pyrogen Test
`(Material Mediated)-IS0
`
`Hemocompatibil ity
`
`C3a Complement Activation
`Assay
`
`Implantation /
`Subchronic toxicity
`
`IS0 Muscle Implantation, in
`3 Rabbits (6 weeks),
`whistopathology
`
`0 1-2293-G4
`The test article must not
`significantly effect the
`clotting time of human
`plasma when compared to
`controls.
`
`01-2293-G2
`The test article must not
`adversely effect selected
`hematological parameters
`of human blood when
`compared to controls.
`0 1 -2293-G 10
`No single animal must
`exhibit an increase of
`0.5"C or more above its
`baseline temperature.
`01T 10878 01
`The test article must not
`induce complement
`activation when compared
`to controls.
`OIC 12404 00
`No capsule formation or
`other adverse reaction to
`the implanted test article.
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Component
`Stent and
`Delivery
`System
`
`Type
`Cytotoxicity
`
`Sensitization
`
`Irritation
`
`Systemic Toxicity
`
`Test
`L929 MEM Elution Test-
`IS0
`
`IS0 Sensitization Study in
`the Guinea Pig
`
`IS0 Acute Intracutaneous
`Reactivity Study in the
`Rabbit
`
`IS0 Acute Systemic
`Toxicity
`in the Mouse
`
`Criterion
`OIC 11441 00
`Results must indicate a grade of
`2 or lower.
`01C 11441 00
`No dermal inflammatory
`response at the test sites greater
`than that seen in the control.
`01C 11441 00
`No adverse reactions or
`responses when compared to
`the controls.
`01C 11441 00
`No greater adverse reactions or
`responses when compared to
`the controls.
`
`Res u Its
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Page 5
`
`Medtronic Exhibit 1823
`
`

`

`Mutagenicity I
`Genotoxicity
`
`Genotoxicity: Bacterial
`Reverse Mutation (Ames)
`Test, Salmonella and E. coli
`Strains
`
`k
`
`Hemocompatibility
`
`Hemolysis
`
`White Blood Cell
`Morphology Study -In vitro
`
`Plasma Recalcification Time
`Coagulation Study (With
`Protocol Amendment I, 11 &
`III)
`voo20-000
`
`IS0 Rabbit Pyrogen Study
`(Material Mediated)
`
`Hemocompatibility
`
`Pyrogenicity
`
`01C 12359 00
`The test article must not induce
`a significant increase in
`reversion in the genomes of the
`organisms tested, when
`compared to controls.
`Test article extracts must not be
`considered mutagenic when
`compared to controls.
`01C 11441 00
`The mean hemolytic index must
`be 2% or less.
`01T 10878 00
`The number of while cells with
`morphological abnormalities
`must be -3%.
`01T 10878 00
`The test article must not exhibit
`a significant difference in
`recalcification times and effects
`on fibrin clot formations when
`comoared to the control.
`OIC 11441 00
`No single animal must exhibit
`an increase of 0.5"c or more
`above its baseline temperature.
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Biocompa
`Component
`Delivery
`System
`
`bility Testing on 1
`Type
`Cytotoxicity
`
`Hemocompatibility
`
`! Multi-Exchange Delivery System
`Test
`Criterion
`L929 MEM Elution Test-
`02T0757800
`Results must indicate a grade of
`I S 0
`2 or lower.
`02T0757800
`The mean hemolytic index must
`be 2% or less.
`
`Hemolysis
`
`C3a Complement Activation
`
`Plasma Recalcification
`
`02T0626800 --
`
`The test article must not induce
`complement activation when
`compared to controls.
`02T0626800
`The test article must not exhibit
`a significant difference in
`recalcification times when
`compared to the control.
`
`Thromboresistance
`
`02T0692000
`Test articles are evaluated for
`the presence of thrombus as
`comoared to the controls.
`
`Resu I ts
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`Pass
`
`13
`
`Page 6
`
`Medtronic Exhibit 1823
`
`

`

`Irritation
`
`IS0 Acute Intracutaneous
`Reactivity
`
`Systemic Toxicity
`
`IS0 Acute System Toxicity
`
`Genotoxicity
`
`Ames
`
`Physicochemical
`
`Physicochemical (aq)
`
`Physicochemical (Non-aq)
`
`Sensitization
`
`IS0 Sensitization
`
`02T0626800
`02T0692000
`No greater adverse reactions or
`responses when compared to
`the controls.
`02T0626800
`02T0692000
`No greater adverse reactions or
`responses when compared to
`the controls.
`02T0626800
`02T0692000
`Test article extracts must not be
`considered mutagenic.
`02T0757800
`Non-volatile residue: < 15mg
`Residue on Ignition: <5mg
`Heavy Metals: 5 lppm
`Buffering Capacity: <lorn1
`02T0757800
`No acceptance criteria have
`been determined. For
`characterization onlv.
`02T0332300
`02T0692000
`96T0594800
`97C0609000
`OOC 10 14200
`No dermal inflammatory
`response at the test sites greater
`than that seen in the control.
`
`Pass
`Pass
`
`Pass
`Pass
`
`Pass
`Pass
`
`Pass
`
`Pass
`
`Pass
`Pass
`Pass
`Pass
`Pass
`
`The Medtronic DriverTM Stent Delivery System successhlly passed all the above
`referenced biocompatibility testing. The DriverTM Over-The-Wire Delivery System was
`not tested since the materials found in it are identical to the materials found in the two
`systems (Rapid Exchange and Multi-Exchange) which passed all tests noted above.
`
`->
`
`Sterilization
`The DriverTM Stent System will be sterilized using Electron Beam sterilization and has
`been validated per AAMIhSO 11 137: Sterilization of health care products - Requirements
`for validation and routine control - Radiation sterilization.
`
`Results obtained from the sterilization studies show that the device satisfies a minimum
`Sterility Assurance Level (S.A.L.) of
`
`In Vitro Testing
`
`In vitro bench testing of the Medtronic DriverTM Stent Delivery Systems was conducted
`in accordance with the FDA ODE “Guidance for the Submission of Research and
`Marketing Applications for Interventional Cardiology Devices: PTCA Catheters,
`
`Page 7
`
`Medtronic Exhibit 1823
`
`

`

`Atherectomy Catheters, Lasers, Intravascular Stents”, May 1995. The relevant tests
`outlined in the guidance were conducted to demonstrate the functional performance
`characteristics of the device.
`
`The following is a brief summary of the bench testing conducted on the device:
`
`Material Analysis (stent)
`This study was conducted to verify that DriverTM stents are produced from material that
`conforms to the chemical composition requirements of ASTM F562-00, “Standard
`Specification for Wrought Cobalt-3 5 Nickel-20 Chromium- 10 Molybdenum Alloy for
`Surgical Implant Applications”. Data for this test was collected from Co-Ni-Cr-Mo alloy
`tubes as processing of this material into a completed stent does not change the overall
`composition of the material. The material used to manufacture the DriverTM stent
`conformed to ASTM F562-00.
`
`Scanning Electron Microscopy (SEM)
`SEM analysis was conducted at 200x magnification to identify trace contaminants that
`may be present on the DriverTM stent surface. No foreign material was observed on any
`of the production lot stents tested. Several small particles inherent to the base stent
`material were observed on the surface, which most probably were exposed during stent
`electropolishing during the manufacturing procedure.
`
`Mechanical Properties
`This testing was conducted to characterize the following mechanical properties of
`annealed Co-Ni-Cr-Mo alloy: 0.2% offset yield strength, ultimate tensile strength, percent
`elongation, and reduction of area. Five (5) tensile bars were machined from barstock
`conforming to ASTM F562-00. The bars were then vacuum annealed to product an
`ASTM grain size of 8.5 in the gage sections. The bars were tensile tested to failure while
`engineering stress and strain were continuously recorded. The offset yield strength,
`ultimate tensile strength, percent elongation, and percent reduction of area for the
`DriverTM stent material are in conformance with ASTM F562-00.
`*
`
`Corrosion
`This test was conducted to evaluate the relative susceptibility to localized corrosion of
`finished Driver stent components. The analysis was based upon ASTM G61 , “Standard
`Test Method for Conducting Cyclic Potentiodynamic Polarization Measurements for
`Localized Corrosion Susceptibility of Iron, Nickel, or Cobalt-Based Alloys”. The results
`indicated that the DriverTM stent possesses a high resistance to the onset of localized
`corrosion.
`
`Stent Free-area
`The Percent Free-Area is a value calculated using Driver stent nominal dimensional
`values and is based in the ratio of stent area to the area of the vessel. Metal to artery
`percentage ratios ranged from 15.4% to 20.5% for 3.0mm to 4.0mm stent, respectively.
`
`Page 8
`
`Medtronic Exhibit 1823
`
`

`

`Length Change vs. Diameter
`This test was performed to determine the change in length as a function of stent internal
`diameter. The testing was performed on complete stent delivery systems that had been
`subjected to all manufacturing and sterilization procedures. Each stent was measured for
`initial length while still on the delivery system, then deployed to nominal pressure of 9
`ATM and measured after removal from the delivery system. Length change ranged from
`-3% to +4% and met the acceptance criteria.
`
`rk
`
`Stent Uniformity
`This test was conducted to demonstrate that the deployed internal diameter of the Driver
`stent is consistent with labeling. The testing was performed on complete stent delivery
`systems that had been subjected to all manufacturing and sterilization procedures. Each
`stent was deployed to nominal pressure of 9ATM. The stent inner diameter was
`measured at each end. All Driver stents met the uniformity expansion specification of +/-
`10% from nominal labeled diameter to 9ATM. The results indicated that the Driver stent
`expands uniformly at all diameters and maintains this uniformity upon withdrawal of the
`balloon.
`
`Radial Strength
`This test is conducted to determine and graphically represent the change in stent internal
`diameter as a function of circumferential pressure and to determine the pressure at which
`deformation is no longer completely reversible for the Driver stent. Fifteen (1 5) 3.0mm
`and fifteen (1 5 ) 4.0mm stents were subjected to all stent-manufacturing procedures. The
`stents were deployed to nominal pressure and removed from the delivery system. The
`stents were placed into a sleeve approximately lmm larger then the stent diameter. A
`vacuum was then applied and outer diameter measurements taken at various pressures.
`All samples maintained a minimum of at least 50 percent of the original stent diameter
`after a 254mm Hg pressure was radially applied. All samples met the acceptance criteria.
`
`Bent Radial Fatigue Testing
`This test was conducted to determine the radial fatigue integrity on a bend of a Driver
`stent under afcelerated cycling designed to test expected in vivo conditions. Eighty-two
`(82) Driver stents were deployed up to a maximum of 5.lmm in distendable tubing and
`attached to fatigue equipment that underwent a 0.005” distention. There were no stent
`failures noted after 420 million cycles which is equivalent to 10 years in vivo.
`
`Stent Recoil
`This test was conducted to quantify the amount of elastic recoil. Fifteen (1 5) stent
`delivery systems of each length and diameter (excluding 30 12 and 40 12) were subjected
`to all manufacturing and sterilization procedures. The stent delivery system was inflated
`to nominal pressure (9ATM) and the stent was removed allowing for recoil to occur. The
`inner diameter at each end of the stent was recorded. Recoil was calculated subtracting
`the recoiled stent inner diameter from the pre-recoil inner diameter. Average recoil
`ranged from 0.002 to 0.004 inches. All stents met the acceptance criteria after balloon
`inflation to nominal pressure.
`
`Page 9
`
`Medtronic Exhibit 1823
`
`

`

`MRI
`Driver Stents were tested to ensure they did not react to a magnetic field in such a manner
`that might pose a clinical issue. The stents should neither deflect nor produce appreciable
`susceptibility image artifacts in the presence of a magnetic field.
`
`Testing for image artifacts created by the Driver stents in a 1.5 Tesla magnetic field
`produced minimal artifact susceptibility. This result was expected in the light of the lack
`of iron in the material composition. The mean deflection angle measured for the Driver
`stent in association with testing performed using a 3.0 Tesla field was 3".
`
`e,
`
`In conclusion, the Driver stents tested did not cause distortion of the magnetic field
`during the MRI procedure. If an implant deflects less than 45", then the magnetically
`induced deflection force is less than the force on the implant due to gravity. Accordingly,
`since the stents tested had a mean deflection of 3", a negligible risk of stent movement in
`a 3.0 Tesla MRI field was indicated.
`
`Stent Expansion
`This test is conducted to determine if the plastic deformation experienced by the stent
`when expanded from the compressed profile to the final maximum deployed diameter can
`produce crack initiation for the Driver stent. Fifteen (1 5) samples from each length and
`diameter (excluding the 30 12 and 40 12) were deployed to their largest possible diameters
`by inflating each delivery system to balloon failure. Each stent was examined at 45X
`magnification for potential cracks. All samples met the acceptance criteria with no
`visible cracks or notches.
`
`Dimensional Verification (stent)
`This test is conducted to verify that dimensional and visual specifications for the Driver
`stent can be achieved. Fifteen (1 5 ) samples from each length within 3.0 and 3.5mm
`diameters were measured with a toolmaker's microscope. All samples met the
`dimensional specifications.
`
`Maximum Pressure (burst test)
`This test is conducted to demonstrate that the delivery system (with mounted stent) will
`not experience balloon, shaft, proximal adaptation or proximal/distal seal loss of integrity
`at or below the pressure required to expand the stent to its labeled diameter. Stent
`delivery systems that had been subjected to all manufacturing and sterilization procedures
`were pressurized to 9Opsi with pressure held for 15 seconds and released for 3 seconds.
`The cycle was then repeated, increasing inflation pressure by 15psi each cycle until
`failure. The shaft of all delivery systems remained intact throughout the test and resulted
`in a labeled rated burst pressure of 16 ATM.
`
`t
`
`Stent Diameter vs. Pressure (stent compliance)
`This test is conducted to quantify the stent inner diameter as a function of balloon
`inflation pressure. Each delivery system was inflated to 6ATM and the outer diameter at
`the distal and proximal point of the stent was measured. This was repeated at 1ATM
`increments. Once the OD measurement was taken at 9ATM, the system was deflated, the
`
`1 '3
`
`Page 10
`
`Medtronic Exhibit 1823
`
`

`

`stent was removed and the inner diameter was measured. The stent was placed back on
`the balloon and continued 1 ATM increments until balloon failure. All stent delivery
`system met the acceptance criteria requirements.
`
`Bond Strength
`This test was performed to provide data to support the bond strength specifications for the
`Driver Stent Delivery Systems. All bonds were trimmed to manageable lengths and
`loaded into the tensile tester and pulled to failure. All samples met the acceptance
`criteria.
`
`a
`
`Diameter and Profile
`This test was conducted to provide dimensional data for the tip, balloon bond, distal shaft,
`intermediate shaft, and proximal shaft of the Driver Coronary Stent System. All catheter
`diameters and profiles met all acceptance criteria.
`
`Balloon Deflatibility
`This test is conducted to provide assurance that the deflated delivery system balloons will
`not interfere with the Driver deployed stent in vivo. Complete stent delivery systems
`were inflated to nominal pressure (9ATM) with a replica vessel placed over the
`premounted stent. The stent delivery system was then deflated and vacuum was drawn,
`allowing the stent to release from the delivery system. All samples passed the acceptance
`requirement of either gravity or vessel release.
`
`Balloon Deflation Time
`This test is conducted to quantify the deflation time of the Driver stent delivery system.
`The complete stent delivery systems were inflated to 9 ATM. Simultaneously, a vacuum
`was pulled and a timer started. The amount of time to deflate the balloon from nominal
`pressures was recorded. The results indicated that all Driver Coronary Stent Systems
`could be deflated within a clinically acceptable time.
`
`Balloon Fatigue
`This report Symmarizes the testing done to satisfy all regulatory requirements for balloon
`fatigue on the Driver Coronary Stent System. The stent delivery systems were repeatedly
`inflated to demonstrate the balloon could sustain multiple repeated inflations. The stent
`delivery systems were capable of at least 20 inflations to rated burst pressure.
`
`Crossing Profile
`This test is conducted to verify the crossing profile as per label claims and to discuss the
`clinical relevance of this test. The stent delivery systems are inserted through a crossing
`profile block until the smallest block that the stent could pass through was determined.
`All samples passed through the 0.056” hole gauge with a maximum observed crossing
`profile of 0.049”.
`
`Tortuous Path
`Stent retention is evaluated using a test which involves tracking the device back and forth
`five times through a track fixture that has four bends of varying tortuosity. After tracking,
`
`Page 11
`
`Medtronic Exhibit 1823
`
`

`

`the force required to remove the stent from the delivery system is measured and the initial
`peak force observed during testing is recorded. Devices are required to meet a pre-
`determined retention force with a 95% confidence and 95% reliability.
`
`In vivo (animal) studies
`Medtronic has conducted six GLP animal studies utilizing the Driver Coronary Stent
`Systems in accordance with 2 1 CFR 0 5 8. These studies evaluated safety, efficacy and
`overall device performance; summaries of these studies are included in the following
`table:
`
`hmrr
`Study
`#
`FS62
`
`FS65
`
`ry of GLP Studies Perform
`Stent Design
`(Delivery System)
`3.04.5mm* dia. x 18mm Ingth.
`(OTW and RX Delivery
`Systems) Control = S7
`3.0-3.5mm dia. x 18mm Ingth.
`(OTW Delivery System)
`Control = S7
`
`FS66
`
`3.0-3.5mm dia. x 18mm Ingth.
`(OTW Delivery System)
`Control = S7
`
`FS67
`
`3.0-3.5mm dia. x 18mm Ingth.
`(OTW Delivery System)
`Control = S7
`
`FS8 1
`
`3.0-3.5mm dia. x 18mm Ingth.
`(OTW Delivery System)
`Control = S7
`
`FS87
`
`Endpoints
`Acute delivery, mechanical
`performance, and chronic
`vascular response.
`Acute delivery and deployment
`performance, angiographic
`estimates of in-stent restenosis at
`sacrifice and histomorphometric
`analysis of histology.
`Acute delivery and deployment
`performance, angiographic
`estimates of in-stent restenosis at
`sacrifice and histomorphometric
`analvsis of histolow.
`Acute delivery and deployment
`performance, angiographic
`estimates of in-stent restenosis at
`sacrifice and histomorphometric
`analysis of histology.
`Acute delivery and deployment
`performance, angiographic
`estimaes of in-stent restenosis at
`sacrifice and histomorphometric
`analysis of histology.
`3.5mm dia. x 18mm Ingth.
`Acute delivery and mechanical
`performance of Over-the-Wire
`(OTW and RX Delivery
`and Rapid Exchange stent
`Systems)
`Control = S7
`systems.
`* The 4.5mm Driver stent was included in this pre-clinical study but is not part of this PMA
`Application
`
`d
`
`# of
`Animals
`
`# of
`Stents
`
`FOIIOW-UP
`Duration
`
`8
`
`6
`
`4
`
`6
`
`6
`
`1
`
`19
`
`28-days
`
`16
`
`28-days
`
`10
`
`90-days
`
`16
`
`180-days
`
`180-days
`
`Acute
`
`Page 12
`
`Medtronic Exhibit 1823
`
`

`

`VIII.
`
`POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH
`
`The Medtronic Driver DeNovo and Restenotic Registry enrolled 298 patients in a non-
`randomized, multi-center study. These patients form the basis of the observed events
`reported in the following section.
`
`Driver DeNovo and Restenotic Registry
`
`A total of 298 patients were enrolled in a multi-center registry to evaluate the safety and
`efficacy of the Medtronic Driver Coronary Stent System for treatment of symptomatic
`coronary artery disease.
`
`rk
`
`The primary endpoint of MACE at 180 days was compared to an objective performance
`criterion (OPC) of 15% based on a pooled MACE rate derived by pooling the data from
`the Bard XT Stent EXTRA RCT, Medtronic Micro Stent I1 SMART RCT, and Medtronic
`BeStent I (BEST) & BeStent I1 Registries.
`
`Adverse events reported during the first six and nine months are shown in the table
`below. A total of 25 of 298 patients (8.4%) who received the Medtronic Driver stent
`experienced one or more adverse events during the nine months of follow-up.
`
`A total of 4 of the 298 (1.3%) patients who received the Driver stent died during the
`clinical study. These out-of-hospital deaths were all non-cardiac related: one secondary
`to ovarian cancer at 43 days post-procedure, one secondary to a brain tumor at 136 days
`post-procedure, one due to acute respiratory failure at 242 days post-procedure and one
`non-specified cancer death at 268 days post-procedure. There were no instances of stent
`thrombosis during the first 270 days. The incidence of vascular complications was 3.4%
`(10/298). The rate of bleeding complications was 2.3% (7/298).
`
`There were no (0/298) delivery or device failures reported.
`Prjpcipal Adverse Events Through 180 & 270-Days
`Driver DeNovo and Restenotic Registry
`%, (Number) [95% confidence interval]
`
`Medtronic Driver Stent (N=298)
`180-Day Results
`7.7% (23)[5.0%,11.4%]
`5.7% (17)[3.4%,9.0%]
`2.0% (6) [0 .7%, 4.3%]
`5.7% (1 7)[3.4%,9.0%]
`1.7% (5)[O. 5%, 3.9%)
`4.0% (12)[2.1%,6.9%]
`0.7% (2)[0.1%,2.4%]
`0.0% (0)[0.0%,1.2%]
`
`Medtronic Driver Stent (N=298)
`270-Day Results
`8.4% (25)[5.5%,12.1%]
`5.7% (1 7)[3.4% ,9 .O%]
`2.7% (8){1.2%,5.2%]
`10.1% (30) [6.9%,14.1%]
`I .7% (5)[0.5°h,3.9%)
`8.4% (25) [5.5%,12.1%]
`1.3% (4) [0.4%, 3.4%]**
`0.0% (0)[0.0%,1.2%]
`
`I.
`
`omplication"
`Adverse Event§
`In-Hospital
`Out-of-Hospital
`MACE
`In-Hospital
`Out-of-Hospital
`
`In-Hospital
`
`Page 13
`
`Medtronic Exhibit 1823
`
`

`

`I n-Hospital
`Out-of-Hospital
`Non Q-wave MI
`In-Hospital
`
`In Hospital -PTCA
`In Hospital-CABG
`Out-of-Hospital PTCA
`d I
`Out-of-HosDital CABG
`-Emergent CABG
`In-Hospital
`Out-of-Hospital
`Stent Thrombosis
`I n-Hospital
`Out-of-Hospital
`Bleeding (procedural transfusion)
`I n-Hospital
`Out-of-Hostital
`CVA
`In-Hospital
`Out-of-Hospital
`Vascular Complications
`In-Hospital
`Out-of-Hospital
`Stent Delivery Failures
`
`0.7% (2)[0.1%,2.4%]
`0.0% (0)[0.0%,1.2%]
`0.0% (0)[0.0%,1.2%]
`0.0% (O)[O.O%, 1.2%]
`1.7% (5)[0.5%,3.9%]
`1.7% (5)[0.5% ,3.9%]
`0.0% (0)[0.0%,1.2%]
`3.4% (10) [1.6%,6.1%]
`0.0% (0)[0.0%,1.2%]
`0.0% (0)[0.0%,1.2%]
`2.7% (8)[1.2%,5.2%]
`0.7% (2) [0.1%,2.4%]
`0.0% (0)[0.0%,1.2%]
`0.0% (0)[0.0%,1.2%]
`0.0% (0)[0.0%,1.2%]
`0.0% (0)[0.0%,1.2%]
`0.0% (0)[0.0%,1.2%]
`0.0% (0)[0.0%,1.2%]
`2.3% (7)[0.9%,4.8%]
`2.0% (6)[0.7%,4.3%]
`0.3% (1)[0.0%,1.9%]
`0.3% (1)[0.0%,1.9%,1
`0.0% (0)[0.0%,1.2%]
`0.3% (1)[0.0%,1.9%]
`3.4% (1 0)[1.6%,6.1 Oh]
`2.7% (8)[1.2%,5.2%]
`0.7% (2)[0.1%,2.4%]
`0.0% (0) [O.O%, 1.2%]
`
`1.3% (4) [0.4%,3.4%]**
`0.0% (0)[0.0%,1.2%]
`0.0% (O)[O.O%, 1.2%]
`0.0% (0)[0.0%,1.2%]
`1.7% (5)[0.5%,3.9%]
`1.7% (5)[0.5%, 3.9%]
`0.0% (0)[0.0%,1.2%]
`7.0% (21) [4.4%, 10.6%)
`0.0% (0)[0.0%,1.2%]
`0.0% (0)[0.00/0,1.2%]
`6.4% (19) [3.9%, 9.8%]
`0.7% (2) [0.1%,2.4%]
`0.0% (O)[O.O%, 1.2%]
`0.0% (0)[0.0%,1.2%]
`0.0% (0)[0.0%,1.2%]
`0.0% (0)[0.0%,1.2%]
`0.0% (0)[0.0%,1.2%]
`0.0% (0)[0.0%,1.2%]
`2.3% (7)[0.9%,4.8%]
`2.0% (6)[0.7%,4.3%]
`0.3% (1)[0.0%,1.9%]
`0.3% (1)[0.0%,1.9%]
`0.0% (O)[O.O%, 1.2%]
`0.3% (1)[0.0%,1.9%]
`3.4% (1 0)[ 1.6% ,6. 1°/o]
`2.7% (8)[1.2%,5.2%]
`0.7% (2)[0.1%,2.4%]
`0.0% (0) [O.O%, 1.2%]
`
`*Complications are based on patient totals. Seven patients had multiple adverse events: one patient hac
`3 vascular complications, four patients had 2 vascular complications), one patient had 1 non-Q MI and 1
`bleeding. complication), and one patient had1 non-Q MI and 1 vascular complication.
`
`'Adverse Event= Death, Q or Non-Q wave MI, Emergent CABG, Stent Thrombosis, CVA, Bleeding
`Complications, and Vaucular Complications.
`*
`**All four deaths were non-cardiac.
`Definitions for the terms used in Table 2 are found in the footnotes to Table 3.
`
`Potential adverse events that may be associated with the use of a coronary stent in native
`coronary arteries (including those listed in Table 2) are listed below in order of severity:
`
`e
`e
`
`e
`e
`e
`e
`
`e
`
`Death
`Emergency Coronary Artery Bypass Graft Surgery (CABG)
`Stroke/Cerebrovascular Accidents
`Cardiac tamponade
`Stent thrombosis or occlusion
`Total occlusion of coronary artery
`Acute myocardial infarction
`
`Page 14
`
`Medtronic Exhibit 1823
`
`

`

`,
`
`Restenosis of stented segments
`Perforation
`Arrhythmias, including ventricular fibrillation & ventricular tachycardia
`Dissection
`Emboli, distal (air, tissue or thrombotic emboli)
`Stent embolization
`Hemorrhage requiring transfusion
`Pseudoaneurysm, femoral
`Spasm
`Myocardial ischemia
`HypotensiodHypertension
`Allergic reaction to drugskontrast mediudstent material
`Peripheral ischemia
`Peripheral nerve injury
`Infection and pain at the insertion site
`Hematoma
`
`IX.
`
`SUMMARY OF CLINICAL STUDIES
`
`Purpose
`
`The purpose of the Driver Registry was to evaluate the safety and efficacy of the
`Medtronic Driver stent for the treatment of single de novo or restenotic post-PTCA (non-
`stented) lesions in native coronary arteries.
`
`Conclusions
`
`The Driver Registry demonstrated the 1 SO-day and 270-day safety and efficacy of the
`Driver stent for treatment of patients with de novo or restenotic lesions in native coronary
`arteries.
`
`Design e
`
`-?-
`
`A prospective, multi-center non-randomized study was conducted in 23 North American
`clinical sites enrolling 298 patients. Patients were 18 years of age or older with clinical
`evidence of ischemic heart disea