perigon pivotal trial review and results · october 2018 medtronic confidential 2 year data...
TRANSCRIPT
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
Design Specifications | 2018 | Confidential8
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
11 Design Specifications | 2018 | Confidential
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
Design Specifications | 2018 | Confidential12
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.
14 Design Specifications | 2018 | Confidential
16 Design Specifications | 2018 | Confidential
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
Avalus Clinical Results| October 2018 | Confidential
Reference: 2 Year Perigon trial data presented by Prof. Klautz at EACTS, October 2018
PRINCIPAL INVESTIGATORS
Prof. Robert Klautz Dr. Joseph Sabik
23 Avalus Clinical Results| October 2018 | Confidential
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%
Avalus Clinical Results| October 2018 | Confidential
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%
Avalus Clinical Results| October 2018 | Confidential
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
26 Avalus Clinical Results| October 2018 | Confidential
VALVE-RELATED ENDPOINT EVENTS VS. OPCANALYSIS BASED ON CEC ADJUDICATED EVENTS
27 Avalus Clinical Results| October 2018 | Confidential
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%
Reference: 2 Year Perigon trial data presented by Prof. Klautz at EACTS, October 2018
28
SURVIVAL
Avalus Clinical Results| October 2018 | Confidential
Reference: 2 Year Perigon trial data presented by Prof. Klautz at EACTS, October 2018
EFFICACY- NYHA CLASSIFICATION AND TRANSVALVULAR LEAK
29 Avalus Clinical Results| October 2018 | Confidential
No moderate TR at 1 year; no severe TR at 2 years.
Pe
rce
nta
ge o
f P
atie
nts
(%
)
Reference: 2 Year Perigon trial data presented by Prof. Klautz at EACTS, October 2018
ECHOCARDIOGRAPHIC FINDINGSALL VALVE SIZES*
30 Avalus Clinical Results| October 2018 | Confidential
Reference: 2 Year Perigon trial data presented by Prof. Klautz at EACTS, October 2018
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
Avalus Clinical Results| October 2018 | Confidential
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
Avalus Clinical Results| October 2018 | Confidential
Reference: 2 Year Perigon trial data presented by Prof. Klautz at EACTS, October 2018
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
Avalus Clinical Results| October 2018 | Confidential
Reference: 2 Year Perigon trial data presented by Prof. Klautz at EACTS, October 2018