PERIGON PIVOTAL TRIAL REVIEW AND RESULTS · october 2018 medtronic confidential 2 year data...

October 2018

MEDTRONIC CONFIDENTIAL2 YEAR DATA PRESENTED BY PROF. KLAUTZ, EACTS, OCTOBER 2018

PERIGON PIVOTAL TRIAL REVIEW

AND RESULTS

G T Stavridis MD FETCS

DISCLOSURES:

Speaker fees from Medtronic

Design specifications

▪ MEDTRONIC CONFIDENTIAL

4

AVALUSTM CE MARK APPROVED!PROVEN PLUS

The Avalus valve leverages proven surgical bioprosthetic valve concepts with added features designed to enhance clinical performance, addressing the contemporary needs of cardiac surgeons as well as patients who are candidates for aortic valve replacement.

PROVEN

• Safety & Efficacy (Perigon Pivotal Trial)

• Interior mounted leaflet Design • AOA Tissue Treatment• Low profile• Flexible and durable sewing cuff• Large EOAs (pending clinical data)

ENHANCEMENTS

• Dual component stent design for strength and durability.

• A softer more pliable cuff design• Narrow flexible stent posts• Designed For durability

PLUS

• Non Metallic MRI Safe• Low profile holder with

a 1 cut release design• 30 second Rinse• Design elements and manufacturing

process to maximize coaptation and minimize central regurgitation

• Geometry to support Valve-in-Valve

PLUSPROVEN

Design Specifications | 2018 | Confidential

5 Presentation Title (Edit on Slide Master) | June 1, 2015 | Confidential, for Internal Use Only

6

THE AVALUS™ Valve

FEATURES

▪ Anti-calcification treatment with alpha amino oleic acid (AOA)

▪ Flexible sewing cuff

▪ Sizes: 17, 19, 21, 23, 25, 27, 29

▪ Bovine, stented, pericardial tissue

▪ Lower profile height

▪ Supra-annular design

▪ Base frame material impregnated with barium sulfate for radiographic visualisation

Avalus™Bioprosthesis

VALVE DESIGN AVALUS BIOPROSTHESIS

• 3 laser cut bovine pericardial leaflets

• Internal mounted leaflets

Supra-annular design

Design Specifications | 2018 | Confidential7

VALVE DESIGN AVALUS BIOPROSTHESIS

▪ Low valve profile

▪ Sewing markers

▪ Soft and pliable sewing cuff


VALVE DESIGN AOA® Tissue Treatment

▪ Mitigate calcification

▪ Over 20 years of clinical use on Medtronic surgical tissue valve portfolio

▪ Mechanism of action is the same in bovine as in porcine tissue

9 Design Specifications | 2018 | Confidential

VALVE DESIGN LEAFLET DESIGN

Laser cut holes in the leaflet are aligned with corresponding holes in stent

▪ Facilitates consistent valve assembly

1

2

3

45

67 8 9 10

1112

1

2

34

5 6 7 89

10

11

12

Central plug used to align leaflets

▪ Consistently sized central hole meeting specification


Tri-leaflet “flexible” support frame

▪Deformation resistant posts

▪Designed to minimize central regurgitation

▪Intended to mitigate high stress zones at tissue attachment points

Non-deformable “firm” base frame

▪Maintain circularity

Dual component polymer frame

▪Strength and flexibility

▪Resistance to permanent deformation

▪No metal components – MRI Safe

▪PEEK base frame impregnated with Barium Sulfate provides for radiopacity and visibility

VALVE DESIGN DUAL COMPONENT PEEK STENT


VALVE DESIGN WEAR TESTING AND ANIMAL STUDY

Accelerated Wear Testing

Assessment of valve durability to 200M cycles or 5 years

Animal Study

90 and 150 day studies used to understand in vivo valve performance in animal (adult sheep)

model.



VALVE SIZINGPROPER USE OF THE AVALUS VALVE SIZER

Step 1: Use the barrel end to determine the initial valve size

Step 2: Use the replica end to check for interference above and below valve

Step 3: Check for interference with larger size

23mm

23mm23mm

*If the potential exists for (a) valve prosthesis interference with coronary ostia, (b) tissue obstruction to valve prosthesis inflow, or (c) distortion of the valve prosthesis stent, consider reorientation of the valve, selecting a smaller valve size, or addressing the obstruction or interference surgically.

Look through the replica to check for valve inflow obstruction *

23mm

In this example, the 25mm valve replica shows tissue interference of the valve prosthesis inflow *

25mm

25mm

17

THE AVALUS™ Valve

FEATURES

▪ Anti-calcification treatment with alpha amino oleic acid (AOA)

▪ Flexible sewing cuff

▪ Sizes: 17, 19, 21, 23, 25, 27, 29

▪ Bovine, stented, pericardial tissue

▪ Lower profile height

▪ Supra-annular design

▪ Base frame material impregnated with barium sulfate for radiographic visualisation

Avalus™Bioprosthesis

Read at the 97th Annual Meeting of The American Association for Thoracic Surgery, Boston, Massachusetts, April 29-May 3, 2017.

METHODS

▪ Primary analysis – comparison of linearized valve-related adverse event rates with the objective performance criteria (OPC) for valve-related event rates

▪ Safety endpoints:

▪ Death▪ Thromboembolism▪ Valve thrombosis▪ Hemorrhage (all and major)▪ Paravalvular regurgitation (all and major)▪ Endocarditis

▪ Effectiveness endpoints:

▪ New York Heart Association (NYHA) functional classification▪ Hemodynamic performance, including effective orifice area (EOA) and mean aortic pressure

gradient

20

KEY SUBJECT SELECTION CRITERIA

Key exclusion criteria:• Pre-existing prosthetic valve/annuloplasty

device in another position or need for replacement/repair of the mitral, pulmonary, or tricuspid valve

•Active endocarditis, active myocarditis, or other systemic infection

•Noncardiac major/progressive disease with life expectancy <2 years

• Renal failure

•Anatomic abnormality that increases surgical risk

• Previous implant and explant of study valve

•Hypoparathyroidism

Key inclusion criteria:

•Moderate or greater AS or AR with clinical indication for valve replacement, with or without

• Left atrial appendage (LAA) ligation

• Coronary artery bypass graft (CABG)

• Patent foramen ovale (PFO) closure

•Ascending aortic aneurysm or dissection repair not requiring circulatory arrest

• Resection of a subaortic membrane not requiring myectomy

Avalus Clinical Results| October 2018 | Confidential

A GLOBAL CLINICAL PROGRAM

Study Milestones

Netherlands

United Kingdom

Germany

Italy

France

Switzerland

Canada

United States

▪EU: 13 Sites▪CAN: 5 Sites▪US: 20 Sites

21 Avalus Clinical Results| October 2018 | Confidential

GLOBAL IMPLANTS BY SITETOP IMPLANTING SITES

Europe

Canada

United States

22

0 20 40 60 80 100 120 140 160

IUCPQ, Quebec City

German Heart Center, Munich

University Hospital, Bordeaux

LUMC, Leiden

The Toledo Hospital, Toledo

St. Thomas Hospital, London

Heart Center, Leipzig

Erasmus MC, Rotterdam

University Hospital, Frankfurt

Toronto General Hospital, Toronto

University of Michigan, Ann Arbor

Houston Methodist Hospital, Houston

Piedmont Hospital, Atlanta

Ottawa Heart Institute, Ottawa

Cardiothoracic and Vascular Surgeons, Austin

Mt. Sinai, New York

University of Cologne, Cologne

Hannover Medical School, Hannover

University Hospital Bichat, Paris

Aurora St. Luke's Medical Center, Milwaukee

University of Washington Medical Center, Seattle

Abbott, Minneapolis

Inselspital - Universitatsspital, Bern

Riverside Methodist Hospital, Columbus

University of Florida Shands, Gainsville

Ospedale S. Raffaele, Milan

Cleveland Clinic, Cleveland

Massachusetts General Hospital, Boston

Montreal Heart Institute, Montreal

Universitatsspital, Zurich

Maimonides Medical Center, Brooklyn

Oklahoma Heart Hospital, Oklahoma City

NY Presb.-Columbia, New York

University of Southern California, Los Angeles

University of Maryland Medical Center, Baltimore

University of Colorado, Denver

Stanford

148

89

70

64

82

45

45

50

36

47

43

46

47

29

30

30

25

18

16

15

13

19

8

8

8

6

6

6

5

4

5

4

5

2

2

1

0


Reference: 2 Year Perigon trial data presented by Prof. Klautz at EACTS, October 2018

PRINCIPAL INVESTIGATORS

Prof. Robert Klautz Dr. Joseph Sabik


BASELINE DEMOGRAPHICS

Characteristic

Subjects

(N=1110)

Age (Mean ±SD) 70.2 ±8.9

% Male 75.0

BSA (Mean ±SD) 2.0 ±0.2

NYHA Class

I 10.9%

II 46.9%

III 40.2%

IV 2.0%

STS Predicted Risk

Mortality 2.0 ±1.4

Morbidity/Mortality 14.7 ±6.0

24

Comorbidity

Subjects

(N=1110)

Rhythm on ECG

Sinus 80.5%

Pacing 2.2%

Atrial Fibrillation 4.1%

Other 13.2%

Hypertension 76.5%

Dyslipidemia 61.8%

Coronary Artery Disease 43.7%

Diabetes 26.8%

CHF 19.9%


PROCEDURE DATAINDICATION FOR SAVR, SURGICAL APPROACH

Procedure Parameter

Subjects

(N=1110)

Primary Indication for Valve Replacement

Aortic Stenosis 84.4%

Aortic Regurgitation 5.7%

Mixed 9.4%

Failed Prosthesis 0.5%

Surgical approach

Median Sternotomy 79.6%

Hemisternotomy 12.9%

Right Thoracotomy 6.2%

Other 1.3%

25

Concomitant Surgical Procedures

Subjects

(N=1110)

None 49.2%

CABG 32.6%

Implantable Cardiac Device (pacemaker,

ICD,

CRT, etc) 0.1%

LAA closure 7.7%

PFO closure 1.2%

Resection of sub-aortic membrane not

requiring myectomy 1.9%

Ascending Aortic Aneurysm not Requiring

Circulatory Arrest 7.6%

Dissection Repair not Requiring Circulatory

Arrest 0.1%


0

50

100

150

200

250

300

350

17 mm 19 mm 21 mm 23 mm 25 mm 27 mm 29 mm

PROCEDURE DATAVALVE IMPLANT DISTRIBUTION BY SIZE

0.1%

3.7%

18.9%

36.1%

31.4%

9.0%

0.8%

• Expected bell curve distribution

• 23mm most common


VALVE-RELATED ENDPOINT EVENTS VS. OPCANALYSIS BASED ON CEC ADJUDICATED EVENTS


1,7

0,10,3 0,1

0,9

2,9

2.0

0

1

2

3

4

5

6

7

8

9

10

Thrombo-embolism

ValveThrombosis

AllPVL

MajorPVL

Endocarditis AllBleeding

MajorBleeding

Eve

nt

Rat

e (

% p

er

valv

e-y

ear

)

Linearized late event rate

5.0

0.4

2.4

1.2

2.4

2.8

1.8

2× OPC

*International Organization for Standardization. Cardiovascular Implants: Cardiac Valve Prostheses. ISO 5840:2009. Geneva, Switzerland.

2-yr Freedom From SVD 100.0%2-yr Freedom From Explant 98.9%


28

SURVIVAL



EFFICACY- NYHA CLASSIFICATION AND TRANSVALVULAR LEAK


No moderate TR at 1 year; no severe TR at 2 years.

Pe

rce

nta

ge o

f P

atie

nts

(%

)


ECHOCARDIOGRAPHIC FINDINGSALL VALVE SIZES*



EU : 470 Subjects

CAN : 267 Subjects

US: 373 subjects

800 Valve-Year Cohort

38 Implanting Centers 1110 Implants Globally

PERIGON ENROLLMENT

31

400 Valve-Year Cohort


0

200

400

600

800

1000

1200

Μαϊ-

14

Ιουν-

14

Ιουλ-

14

Αυγ-

14

Σεπ

-14

Οκτ

-14

Νοε-

14

Δεκ

-14

Ιαν-

15

Φεβ

-15

Μαρ

-15

Απρ

-15

Μαϊ-

15

Ιουν-

15

Ιουλ-

15

Αυγ-

15

Σεπ

-15

Οκτ

-15

Νοε-

15

Δεκ

-15

Ιαν-

16

Φεβ

-16

Μαρ

-16

Απρ

-16

Μαϊ-

16

Ιουν-

16

Ιουλ-

16

Αυγ-

16

Σεπ

-16

Οκτ

-16

Νοε-

16

Δεκ

-16

Ιαν-

17

Φεβ

-17

Μαρ

-17

Απρ

-17

Μαϊ-

17

Ιουν-

17

Ιουλ-

17

32

SUBJECT FLOW

Subjects enrolledN = 1230

Baseline evaluationN = 1250

Procedure evaluationN = 1110

Discharge evaluationN = 1105

3- to 6-month evaluationN = 1081

1-year evaluationN = 921

Died n = 1Withdrew n = 139

Died n = 5

Died n = 14Withdrew n = 5Explant n = 5

Died n = 14Withdrew n = 8LTFU n = 3 Explant n = 3Missed n = 10Pending n=132



33 Presentation Title (Edit on Slide Master) | June 1, 2015 | Confidential, for Internal Use Only

SENSIBLE COMMENTS BY EXPERTS IN THE FIELD

VIV made easier ??

34

CONCLUSIONS

▪ The PERIGON Pivotal Trial demonstrates the safety and effectiveness of the Avalus bovine pericardial stented

valve

▪ Overall mortality and valve-related events are very low

▪ Mean gradients are comparable to or lower than for other valves

▪ Central regurgitation compares favourably to other valves



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PERIGON PIVOTAL TRIAL REVIEW AND RESULTS · october 2018 medtronic confidential 2 year data...

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