Caution: Investigational Device. Limited by Federal (USA) Law to investigational use. AMEthyst The...

Caution: Investigational Device. Limited by Federal(USA) Law to investigational use. AMEthyst

The AMEthyst TrialThe AMEthyst TrialA prospective randomized controlled study of the A prospective randomized controlled study of the

Medtronic Interceptor® PLUS Coronary Filter System Medtronic Interceptor® PLUS Coronary Filter System for PCI of Degenerative SVGfor PCI of Degenerative SVG

Dean KereiakesDean KereiakesM. Turco, B, McLaurin, R. Feldman, N. M. Turco, B, McLaurin, R. Feldman, N.

Farhat, J. Breall and M.Foster Farhat, J. Breall and M.Foster on behalf of the study investigatorson behalf of the study investigators

Late Breaking Clinical Trial Presentation

TCT 2007


Dean J. Kereiakes, M.D., FACC Disclosure:Dean J. Kereiakes, M.D., FACC Disclosure:

SCIENTIFIC ADVISORY BOARD:•Cordis/Johnson & Johnson•Boston Scientific Corporation, Inc.•Abbott Vascular•Core Valve

RESEARCH GRANT SUPPORT:•Boston Scientific Corporation Inc.•Abbott Vascular•Medtronic•Daiichi Sankyo

CONSULTING:•Eli Lilly Co.•Daiichi Sankyo•Medtronic


AMEthystAMEthyst

Medtronic Interceptor PLUS Filter CatheterMedtronic Interceptor PLUS Filter Catheter Study Device

Nitinol Filter Basket 71% Open pore area

Low profile 2.7 Fr0.0014” wire

Actuator handle

100 µ distal pores

1400-1800 µ proximal openings


AMEthystAMEthyst

InvestigatorInvestigator HospitalHospital# #

PatientsPatients

B. McLaurinB. McLaurin Anderson Area Med. Ctr.Anderson Area Med. Ctr. 6565

R. FeldmanR. Feldman Munroe Regional Med. Ctr.Munroe Regional Med. Ctr. 6363

N.FarhatN.Farhat EMH Regional HospitalEMH Regional Hospital 6262

D. Kereiakes*D. Kereiakes* Christ HospitalChrist Hospital 4444

J. BreallJ. Breall Indiana University Med. Ctr.Indiana University Med. Ctr. 4444

M. FosterM. Foster Providence HospitalProvidence Hospital 3232

A. RabinowitzA. Rabinowitz Texsan/SW TexasTexsan/SW Texas 2525

J. PattersonJ. Patterson Forsyth Med. Ctr.Forsyth Med. Ctr. 2424

A. SzyniszewskiA. Szyniszewski St. Joseph MercySt. Joseph Mercy 2323

K. SmithK. Smith University of FloridaUniversity of Florida 2020

* Principal Investigator

Enrollment : 73 U.S. Centers - “Top 10”


Randomized, Open Label, Multicenter Trial

AMEthyst: Study DesignAMEthyst: Study Design

Primary EndpointPrimary Endpoint:: MACE (death, MI, repeat revascularization) at 30 daysMACE (death, MI, repeat revascularization) at 30 daysSecondary Endpoints:Secondary Endpoints: Elevated CK, CK-MB during index hospitalization, in hospital MACE, Elevated CK, CK-MB during index hospitalization, in hospital MACE, device and clinical successdevice and clinical success

Primary EndpointPrimary Endpoint:: MACE (death, MI, repeat revascularization) at 30 daysMACE (death, MI, repeat revascularization) at 30 daysSecondary Endpoints:Secondary Endpoints: Elevated CK, CK-MB during index hospitalization, in hospital MACE, Elevated CK, CK-MB during index hospitalization, in hospital MACE, device and clinical successdevice and clinical success

30 days30 days

De Novo or restenotic lesions of Saphenous Vein Grafts

Vessel Diameter: 2.5-5.25mm

De Novo or restenotic lesions of Saphenous Vein Grafts

Vessel Diameter: 2.5-5.25mm

Control DEP*Control DEP*n = 200n = 200

Control DEP*Control DEP*n = 200n = 200

Interceptor® PLUSInterceptor® PLUSn= 600n= 600

Interceptor® PLUSInterceptor® PLUSn= 600n= 600

2:1 randomization2:1 randomization

Clinical ProcedureClinical Procedure

*GuardWire® or FilterWireTM EZ at physician’s discretion


AMEthystAMEthyst

Includes multivessel PCI with following restrictions:Includes multivessel PCI with following restrictions:Total of 2 lesions in up to 2 native vessels (non-target lesions [NTL])Total of 2 lesions in up to 2 native vessels (non-target lesions [NTL])NTLs successfully treated before enrollment to studyNTLs successfully treated before enrollment to studyUnlimited target lesions (TL) in up to 2 SVG’sUnlimited target lesions (TL) in up to 2 SVG’s

Key Inclusion Criteria:Key Inclusion Criteria:Subjective or ObjectiveSubjective or Objective evidence of ischemiaevidence of ischemiaTL in a SVG TL in a SVG >>50 and <100% stenosed50 and <100% stenosedTarget Vessel has TIMI 1 flow or greaterTarget Vessel has TIMI 1 flow or greater

Key Exclusion Criteria:Key Exclusion Criteria:Recent Myocardial Infarction (MI) Recent Myocardial Infarction (MI) >>24 hrs, with + CK-MB, or Acute MI24 hrs, with + CK-MB, or Acute MISurgery within 30 daysSurgery within 30 daysLVEF <25%LVEF <25%TL has been previously stentedTL has been previously stentedTL within 5mm of graft ostium or TL within 5mm of graft ostium or <<35mm from graft-native anastomosis 35mm from graft-native anastomosis

Subject Selection Criteria


AMEthystAMEthyst

Core LabsQCA Core LabQCA Core Lab– Brigham and Women’s Hospital, Boston, MA, USA Brigham and Women’s Hospital, Boston, MA, USA – Jeffrey J. Popma, MDJeffrey J. Popma, MD

Data Coordinating CenterData Coordinating Center– Harvard Clinical Research Institute, Boston, MA, USA Harvard Clinical Research Institute, Boston, MA, USA – Laura Mauri, MDLaura Mauri, MD

ECG Core LabECG Core Lab

– Harvard Clinical Research Institute, Boston, MA, USAHarvard Clinical Research Institute, Boston, MA, USA

– Peter Zimetbaum, MDPeter Zimetbaum, MD

Clinical Events Committee/DSMBClinical Events Committee/DSMB– Harvard Clinical Research Institute, Boston, MA, USA Harvard Clinical Research Institute, Boston, MA, USA – Donald Cutlip, MDDonald Cutlip, MD


2:1 Randomization

Ratio

AMEthystAMEthystSample Size Calculation

INITIAL ASSUMPTIONS:

• D30 MACE rate for Interceptor and Control group <10%

• Power 80%

• 1-sided alpha error 5%

• Delta for equivalence 5.5%

Interceptor PLUS

400 patients

Control Device

200 Patients

600 Patients

SAFER Trial

Borrow additional patients using Bayesian methods


Revised Sample Size CalculationsRevised Sample Size Calculations

DSMB Safety Review 04/18/05

(first 300 patients)

No Safety Issues

However:

• Observed control 30D MACE <<10%

•? Pooling with SAFER patients

•? Study Adequately Powered

Continue Study

Add 200 patients

AMEthystAMEthyst

Revised Assumptions

• 30D MACE rate for control and Interceptor assumed < 6%

• Power 80%

• 1-sided alpha error 5%

• Delta for equivalence 4.5%


AMEthyst AMEthyst Final Patient Distribution and Follow-upFinal Patient Distribution and Follow-up

Patients Enrolledn=800

Randomized2:1

Interceptorn = 533

Control DEPn = 267

Clinical F/U30 days258/26597.4%

Clinical F/U30 days522/53397.9%

GuardWiren= 194

FilterWire*n=73

*Additional optional control device added per Amendment Feb 2006


AMEthystAMEthystPatient Demographics

Interceptor Interceptor PLUSPLUSn=533n=533

Control Control DEPDEP

n=267n=267

p valuep value

Male (%)Male (%) 79.479.4 78.378.3 0.710.71

Age (yrs+SD)Age (yrs+SD) 6969++10.2210.22 68.268.2++10.3510.35 0.270.27

Diabetes (%)Diabetes (%) 45.145.1 43.843.8 0.760.76

Hypertension (%)Hypertension (%) 86.186.1 87.687.6 0.580.58

Dyslipidemia (%)Dyslipidemia (%) 91.391.3 93.293.2 0.410.41

Unstable Angina (%)Unstable Angina (%) 60.660.6 61.461.4 0.880.88

Left Ventricular Ejection Fraction (%Left Ventricular Ejection Fraction (%++SD)SD) 50.750.7++11.611.6 51.551.5++11.611.6 0.390.39

Prior PCI to target lesion (%)Prior PCI to target lesion (%) 10.310.3 10.810.8 0.900.90


AMEthystAMEthyst

InterceptorInterceptorn = 533n = 533

ControlControln = 267n = 267 p valuep value

Age of SVG (yrs)Age of SVG (yrs) 11.1011.10++5.665.66 10.3710.37++5.465.46 0.090.09

B2/C lesions (%)B2/C lesions (%) 75.375.3 74.874.8 0.860.86

RVD (mm)RVD (mm) 3.273.27++0.690.69 3.223.22++0.610.61 0.290.29

Lesion Length (mm)Lesion Length (mm) 14.2814.28++9.739.73 14.4914.49++4949 0.760.76

Pre-procedure MLD (mm)Pre-procedure MLD (mm) 1.141.14++0.550.55 1.131.13++0.580.58 0.730.73

Post- procedurePost- procedure

In-Stent MLD (mm)In-Stent MLD (mm) 3.513.51++0.620.62 3.403.40++0.650.65 0.020.02

In-stent % stenosisIn-stent % stenosis -7.77-7.77++11.111.1 -5.38-5.38++14.2914.29 0.020.02

Procedural and Lesion CharacteristicsProcedural and Lesion Characteristics


SVG Degenerative Score (% lumen irregularities )Am J Cardiol 2005; 95(2) 173-7

0 (0-25%) 1 (26-50%)

2 (51-75%) 3 (76-100%)



ControlControln = 267n = 267 p valuep value

0.720.72

0-25%0-25% 44.844.8 43.443.4

26-50%26-50% 35.535.5 36.136.1

51-75%51-75% 15.615.6 16.416.4

76-100%76-100% 4.14.1 4.04.0

AMEthystAMEthyst

Extent of SVG DegenerationExtent of SVG Degeneration



ControlControln = 267n = 267 p p valuevalue

Number of Stents/PtNumber of Stents/Pt 1.28± 0.581.28± 0.58 1.39± 0.781.39± 0.78 0.10.1

Total Stent Length (mm)Total Stent Length (mm) 25.8 ±16.325.8 ±16.3 27.1 ±15.627.1 ±15.6 0.270.27

Stent:Lesion LengthStent:Lesion Length 1.58 ±0.691.58 ±0.69 1.61 ±1.221.61 ±1.22 0.680.68

Stent diameterStent diameter 3.0 mm (%)3.0 mm (%) 18.218.2 20.120.1 0.340.34

3.5 mm (%)3.5 mm (%) 4.0 mm (%)4.0 mm (%)

46.146.119.219.2

45.145.117.417.4

Max Deployment (ATM)Max Deployment (ATM) 16.1 ±3.316.1 ±3.3 15.8 ±3.815.8 ±3.8 0.380.38

Max Inflation (ATM)Max Inflation (ATM) 16.4 ±3.416.4 ±3.4 16.2 ±4.016.2 ±4.0 0.390.39

GP IIb/IIIa Inhibitor (%)GP IIb/IIIa Inhibitor (%) 40.040.0 39.339.3 0.880.88

AMEthystAMEthystProcedural CharacteristicsProcedural Characteristics


InterceptorInterceptorn=533n=533

ControlControln=267n=267 p p ValueValue

Death % (#)Death % (#) 00 0.7 (2)0.7 (2) 0.110.11

MI % (#)MI % (#) 7.3 (39)7.3 (39) 5.2 (14)5.2 (14) 0.300.30

Q WaveQ Wave 0.40.4 0.70.7 0.600.60

Non-Q waveNon-Q wave 6.9 (37)6.9 (37) 4.5 (12)4.5 (12) 0.210.21

Stent Thrombosis % (#)Stent Thrombosis % (#) 00 00

MACE % (#)MACE % (#) 7.3 (39)7.3 (39) 5.6 (15)5.6 (15) 0.460.46

AMEthystAMEthyst

Outcomes – in hospital


Device success defined as delivery, deployment and retrieval of the assigned device

Clinical success defined as delivery, deployment and retrieval of the assigned device with no in hospital MACE


ControlControln=267n=267 p p valuevalue

Device Success (%)Device Success (%) 90.590.5 93.893.8 0.130.13

Clinical Success (%)Clinical Success (%) 85.485.4 89.689.6 0.120.12

Final TIMI Flow (%)Final TIMI Flow (%) 0.510.51

00 00 0.70.7

11 00 00

22 1.91.9 1.81.8

33 98.198.1 97.497.4

AMEthystAMEthystDevice Effectiveness (ITT population)



ControlControln=250n=250 p p ValueValue

Death % (#)Death % (#) 00 0.8 (2)0.8 (2) 0.110.11

MI % (#)MI % (#) 8.0 (40)8.0 (40) 6.0 (15)6.0 (15) 0.370.37

Q WaveQ Wave 0.4 (2)0.4 (2) 0.8 (2)0.8 (2) 0.600.60

Non Q waveNon Q wave 7.6 (38)7.6 (38) 5.2 (13)5.2 (13) 0.280.28

Stent Thrombosis % (#)Stent Thrombosis % (#) 0.4 (2)0.4 (2) 0.8 (2)0.8 (2) 0.600.60

TLR % (#)TLR % (#) 0.2 (1)0.2 (1) 0.4 (1)0.4 (1) 1.001.00

TVR (non-TL) % (#)TVR (non-TL) % (#) 00 1.2 (3)1.2 (3) 0.040.04

MACE % (#)MACE % (#) 8.0 (40)8.0 (40) 7.2 (18)7.2 (18) 0.770.77

AMEthystAMEthyst Outcomes to 30 days


Control(n=18/250)

Interceptor(n=40/501)

7.2%7.2%8.0%8.0%

30 day MACE

P for Non-Inferiority 0.027 (for delta=4.5%)P for difference 0.77

AMEthystAMEthystPrimary Endpoint


ConclusionsConclusions

The InterceptorThe Interceptor®® PLUS filter is not inferior in safety PLUS filter is not inferior in safety and efficacy to 30 days when compared with and efficacy to 30 days when compared with currently approved DEP device standards currently approved DEP device standards (GuardWire, FilterWire EZ).(GuardWire, FilterWire EZ).

A trend toward less frequent TVR (non-TL) to 30 days A trend toward less frequent TVR (non-TL) to 30 days observed following Interceptor (vs. Control DEP)observed following Interceptor (vs. Control DEP)

Overall MACE to 30 days in DEP device-treated Overall MACE to 30 days in DEP device-treated patients appears to be less frequent in contemporary patients appears to be less frequent in contemporary PCI practice and deserves further study.PCI practice and deserves further study.

AMEthyst

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