these materials are provided to you strictly for your use in preparing to and participating in the...

These materials are provided to you strictly for your use in preparing to and participating in the SURTAVI Trial.CAUTION – Investigational device. Exclusively for Clinical Investigations. . ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français.

Medtronic CoreValve® SURTAVI Trial

SUrgical Replacement and Transcatheter Aortic Valve Implantation

UC201204978b EE


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Medtronic TAVI Clinical Research Portfolio

Demonstrate Safety and Efficacy

Expand Access to New Populations and Markets

Confirm Efficacy and Optimize Practice


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• Management of Severe Aortic Stenosis in intermediate risk patients

• CoreValve SURTAVI Trial o Inclusion Criteriao Exclusion Criteria o Study Investigatorso Current Status

• Comparisons o US Pivotal Trial and SURTAVI Trial o SURTAVI Trial and PARTNER II A


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CoreValve® SURTAVI Trial Overview1

• Randomized 1:1, non-inferiority study

• The trial will be conducted at up to 115 worldwide centers• Europe• Canada• United States

• Long-term follow-up through 5 years

• Approximately 2,500 subjects

1. Medtronic CoreValve® SURTAVI Trial. Version 6.0. Mounds View, MN: Medtronic, Inc. Clinical Research; 2013.


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• Severe, symptomatic AS

• Intermediate surgical risk, defined by Society of Thoracic Surgeons (STS) mortality risk of ≥ 4% and ≤ 10%

CoreValve® SURTAVI Trial Patient Population


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CoreValve® SURTAVI Trial Study Design

RandomizationStratified by need for

revascularization

SAVRMedtronic CoreValve® TAVI

N = ~2,500 patients

TAVI onlyTAVI + PCI SAVR onlySAVR + CABG

STS mortality risk ≥4% and ≤10%

Heart Team EvaluationConfirm Inclusion/Exclusion &

Intermediate Risk Classification

Baseline Neurological Assessments


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CoreValve® SURTAVI Trial1

Primary Objective and Endpoint

Primary ObjectiveEvaluate in a prospective randomized fashion whether TAVI is non-inferior to SAVR with respect to composite endpoint of all-cause mortality and disabling stroke at 24 months in patients with symptomatic severe aortic stenosis and at intermediate surgical risk

Primary EndpointAll-cause mortality or disabling stroke at 24-months



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Secondary Objectives

Secondary Objective •Assess differences in quality of life, clinical benefit (efficacy endpoints) and health economics in patients with symptomatic severe aortic stenosis and at intermediate risk treated with either Transcatheter Aortic Valve Implantation (TAVI) or Surgical Aortic Valve Replacement (SAVR)

Exploratory Objective •An analysis will be conducted to determine if patients can be identified as intermediate risk for Transcatheter Aortic Valve Implantation (TAVI) based upon age and the presence of a defined list of co-morbidities commonly associated with patients undergoing TAVI procedures



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Device and Access Routes

• CoreValve® System

• 23mm, 26mm, 29mm, 31mm

• Alpha-amino oleic acid (AOA®) antimineralization treatment

• Access Routes

• Transfemoral

• Subclavian

• Direct Aortic



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Coronary Artery Disease

• Subjects with CAD and a Syntax score ≤22 will be eligible

• Concomitant PCI and TAVI can be performed; staging is left at discretion of operator

• CABG should be conducted during the index SAVR procedure

• Randomization stratified by need for coronary revascularization


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Frailty Assessment

• Frailty assessments identifies:– Subject is < 80 years of age and three or more of the following

apply

– Subject is ≥ 80 years of age and two or more of the following apply• Wheelchair bound• Resides in an institutional care facility (e.g. nursing home,

skilled care center)• Body Mass Index < 20 kg/m2

• Grip strength < 16kg• Katz Index Score ≤ 4• Albumin < 3.5 g/dl



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Inclusion Criteria

1. Subject must have STS mortality risk score of ≥ 4% and ≤ 10%

2. Heart Team consisting of at least one interventional cardiologist and one cardiac surgeon agree on indication, treatment proposal, and eligibility for randomization based on their clinical judgment



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Inclusion Criteria (cont.)

3. Subject has severe aortic valve stenosis presenting with:

a) Critical aortic valve area defined as an initial aortic valve area of ≤1.0 cm2 or aortic valve area index < 0.6 cm2/m2

AND

b) Mean gradient > 40mmHg or Vmax > 4.0m/sec by resting echocardiogram [or dobutamine stress echocardiogram, if subject has a left ventricular ejection fraction (LVEF) <55%] or velocity ratio < 0.25

4. Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York Heart Association (NYHA) Functional Class II or greater



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Inclusion Criteria (cont.)

5. Subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits

6. Subject meets the legal minimum age to provide informed consent based on local regulatory requirements



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Key Exclusion Criteria

• Subject has refused surgical aortic valve replacement (SAVR) as a treatment option

• Multivessel coronary artery disease with a Syntax score >22

• Extensive mediastinal radiation

• Liver failure (Child-C)



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Key Exclusion Criteria1 (cont.)

• Reduced ventricular function with left ventricular ejection fraction (LVEF) <20% as measured by resting echocardiogram

• Pulmonary Hypertension > 80mmHg

• Severe Chronic Obstructive Pulmonary Disease (COPD) demonstrated by Forced Expiratory Volume (FEV1) < 750cc



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CoreValve® SURTAVI TrialStudy Investigators

Chairman

Prof. P.W. Serruys (Chair)

Dr. N. Van Mieghem (Deputy Chair)

Principal Investigators

Prof. S. Windecker Dr. J. Popma

Prof. A.P. Kappetein Dr. D. Adams

Prof. R. Lange Dr. M. Reardon

Prof. T. Walther


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CoreValve ® SURTAVI TrialUS Clinical Sites

Active Site


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Beth Israel Deaconess Medical Center Boston, MA

Duke University Medical Center Durham, NC

Geisinger Medical Center Danville, PA

Iowa Heart Center Des Moines, IA

Johns Hopkins Hospital Baltimore, MD

Morristown Memorial Hospital Morristown, NJ

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2

3

7

8

9

4

Pinnacle Health Harrisburg, PA

Riverside Methodist Hospital/Ohio Health Research InstituteColumbus, OH

Spectrum Health Hospitals Grand Rapids, MI

St. Francis Hospital Roslyn, NY

St John Hospital and Medical CenterDetroit, MI

St. Luke's Medical Center/Aurora Health CareMilwaukee, WI

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6

10

11

12

CoreValve ® SURTAVI TrialUS Clinical Sites - Activated


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The Mount Sinai Medical Center New York, NY

The Ohio State University Medical Center/The Richard M. Ross Heart Hospital Columbus, OH

University of Kansas Hospital Kansas City, KS

University of Michigan Health Systems Ann Arbor, MI

University of Pittsburgh Medical Center Pittsburgh, PA

University of Southern California Los Angeles, CA

Vanderbilt University Medical Center Nashville, TN

Wake Forest University/Baptist Medical Center Winston-Salem, NC

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18

19

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14

15

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CoreValve ® SURTAVI TrialUS Clinical Sites - Activated (cont.)

Baylor Heart & VascularDallas, TX

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22 Hartford HospitalHartford, CT

23 Methodist DeBakey Heart & VascularHouston, TX

24 University Hospital/Case Medical CenterCleveland, OH

25 Detroit Medical CenterDetroit, MI

26 North Shore University HospitalManhasset, NY

Loyola University Medical CenterMaywood, IL

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28

29

Cardiovascular Institute of the SouthHouma, LA

VA Palo AltoPalo Alto, CA


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CoreValve ® SURTAVI TrialUS Clinical Sites – Activated (cont.)

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Fletcher Allen Health CareBurlington, VT

NYU-Langone Medical Center New York, NY

El Camino HospitalMountain View, CA

Kaiser PermanenteLos Angeles, CA

Lenox Hill HospitalNew York, NY

University of MiamiMiami, FL

Yale New Haven HospitalNew Haven, CT

Piedmont Heart InstituteAtlanta, GA

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31

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Scripps Green HealthLa Jolla, CA

Washington Hospital CenterWashington, DC

Columbia University Medical CenterNew York, NY

Good Samaritan Hospital Cincinnati, OH

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41


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CoreValve ® SURTAVI TrialEuropean Clinical Sites

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2

3 4

5

6

7

8

1011

12

13

15

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Erasmus Medical CenterRotterdam, Netherlands

Inselspital - Universitatsspital BernBern, Switzerland

Leeds General InfirmaryLeeds, UK

Medisch Centrum LeeuwardenLeeuwarden, Netherlands

RighospitaletCopenhagen, Denmark

St. Antonius ZiekenhuisNieuwegein, Netherlands

Universitatsspital ZurichZurich, Switzerland

Hospital Universitario Central de AsturiasOviedo, Spain

Hospital Universitario Virgen de la Victoria Malaga, Spain

CoreValve ® SURTAVI TrialEuropean Clinical Sites - Activated

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2

3

4

5

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7

8

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St. George’s HospitalLondon, UK

Royal Sussex County HospitalBrighton, UK

Amphia HospitalBreda, Netherlands

Karolinska University HospitalStockholm, Sweden

German Heart CenterMunich, Germany

University HospitalBonn, Germany

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1011

12

13

1014

15


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CoreValve ® SURTAVI TrialCanadian Clinical Sites

Montreal Heart InstituteMontreal, Quebec

Royal VictoriaMontreal, Quebec

University of Ottawa Heart InstituteOttawa, Ontario

London Health Sciences Center/ University HospitalLondon, Ontario

Toronto General HospitalToronto, Ontario

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2

3

123

4

45

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ComparisonSURTAVI Trial and US Pivotal Trial

SURTAVI US Pivotal Extreme Risk

US PivotalHigh Risk

Patient Population Symptomatic severe AS at intermediate surgical risk: STS mortality risk of ≥4% and ≤10%

Symptomatic severe AS, with predicted operative mortality or serious, irreversible morbidity risk of ≥ 50% at 30 days.

Symptomatic severe AS, with predicted risk of operative mortality is ≥15% (and predicted operative mortality or serious, irreversible morbidity risk of < 50%) at 30 days.

Concomitant Coronary Revascularization

Allowed Excluded Excluded

Sample Size ~ 2,500 (adaptive design) 1597 (including High Risk) 1597 (including Extreme Risk)

Geography US, Europe, Canada US US

# of Worldwide Sites 115 45 45

Definition of Severe AS

Initial AVA of ≤1.0 cm2 or AVA index < 0.6 cm2/m2

Initial AVA of ≤ 0.8 cm2 (or AVA index ≤ 0.5 cm2/m2)

Initial AVA of ≤ 0.8 cm2 (or AVA index ≤ 0.5 cm2/m2)

Primary Endpoint All-cause mortality or disabling stroke at 24 months

All-cause death or majorstroke at 12 months

All-cause mortality at 12 months

Neuro Sub-Study Required in primary protocol Separate sub-study Separate sub-study

Key Exclusion Criteria Differences

True Porcelain Aorta; Extensive Mediastinal Radiation; Liver failure (Child –C); Frailty Assessments; Marfan Syndrome; Uncontrolled AF; Pulmonary HTN; Severe COPD


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SURTAVI PARTNER II A≥4 and ≤ 10 STS Inclusion ≥4

>22 Syntax Exclusion >32

AVA ≤ 1.0cm2

Indexed AVA < 0.6 cm2/m2

Valve Area Inclusion AVA ≤ 0.8cm2

Indexed EOA < 0.5cm2/m2

Discharge, 30 days, 3 months, 6 months, 12 months, 18 months, 24 months, annually for

5 years

Follow-up Visits Discharge, 30 days, 6 months, 1 year, annually for

5 years

Global (US, Europe, Canada)up to 115 centers

Geography United States and Canada (2) (57 centers total)

ComparisonSURTAVI Trial and PARTNER II A


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