TCT2015 Presentation - Philippe Généreux, M.D.

1. Philippe Généreux, MD
for the Tryton Bifurcation Trial Investigators
Columbia University Medical Center
Cardiovascular Research Foundation
New York City
The TRYTON PIVOTAL:
Randomized Trial & Confirmatory Study
Dedicated Bifurcation Stent in Coronary Bifurcation
Involving Large Side Branches
TCT 2015, October 12th, 2015

2. Disclosure Statement of Financial Interest
Philippe Généreux, MD
Within the past 12 months, I or my spouse/partner have had a financial
interest/arrangement or affiliation with the organization(s) listed below.
• Institutional Research Support
• Consulting Fees/Honoraria
• TRYTON Medical, Boston Scientific,
Cardiovascular System inc.
• Abbott Vascular, Cardiovascular
System Inc, Pi Cardia, Edwards
Lifesciences
Affiliation/Financial Relationship Company

3. Bifurcation Lesions
Still a Challenge
• Require more time, anxiety,
skill, and equipment (cost)
• Increased complications
peri-procedural MIs,
stent thrombosis, and
restenosis
• Suboptimal angiographic
outcomes (esp. side branch
ostium)

4. Randomized Bifurcation Stent Studies
(NORDIC, BBC ONE, CACTUS)

5. TRYTON Side Branch Stent
Transition
Zone
Side Branch
Zone
Main Branch
Zone
8 mm 4.5 mm 6.5 mm
Tryton is a Cobalt alloy bare metal stent

6. Tryton Side Branch Stent Sizes

7. Tryton Deployment Sequence
Tryton positioned
and deployed after
pre-dilatation
(secures and protects
side branch)
Main vessel treated
with approved DES
through main
vessel portion of
Tryton
Kissing balloon
post-dilatation to
insure complete lesion
& ostium coverage

8. TRYTON Pivotal RCT
Généreux et al. J Am Coll Cardiol 2015;65:533–43

9. Tryton Study Design
DES (main vessel) +
Provisional side branch
Baseline Angiography – Eligible for Randomization
True bifurcation with SB≥ 2.5mm by visual estimation
Angiographic F/U
at 9 months
Clinical F/U
at 9 months





% DS side branch
n~374
Tryton side branch +
DES (main vessel)

TVF
Primary Endpoint

N = 704
IVUS F/U
at 9 months

IVUS Cohort
n~96
Clinical F/U
at 9 months
Angiographic F/U
at 9 months
IVUS F/U
at 9 months

10. Provisional (n= 349)
Tryton (n= 355)
Additional Side Branch Stents
(Site Reported)

11. TRYTON Pivotal RCT
Primary Non-Inferiority Endpoint
Not Met
%
12.8
0
10.7
3.6
17.4
0
15.1
4.7
0
2
4
6
8
10
12
14
16
18
20
TVF Cardiac Death Target Vessel MI Clinically Driven TVR
Non Hierarchical
P= 0.11
P = 0.11
P =0.56
Provisional
Tryton
Généreux et al. J Am Coll Cardiol 2015;65:533–43

12. 38.6
31.6
0
10
20
30
40
50
60
P=0.002
Provisional
Tryton
Side Branch %DS (In-segment)
Secondary Endpoint
%
Secondary Superiority Endpoint Met
Angiographic Cohort n=326
Généreux et al. J Am Coll Cardiol 2015;65:533–43

13. 14
33
49
152
164
104
66 68
24
10 11
60
20
40
60
80
100
120
140
160
180
≥ 2.25 mm:
41% of ITT lesions
Side Branch RVD (Core Lab)#Frequency
Pre Procedure Side Branch Size

14. TRYTON Large SBs Sub-Analysis:
Side Branches ≥2.25mm
Généreux et al. Catheter Cardiovasc Interv. 2015

15. Provisional (n= 143)
Tryton (n= 146)
Side Branch Bail Out Stenting
Nearly Eliminated in Tryton Group
Side Branch ≥ 2.25 mm

16. %
15.6
0
12.1
4.3
11.3
0
9.2
3.5
0
2
4
6
8
10
12
14
16
18
TVF Cardiac Death Target Vessel MI Clinically Driven TVR
P= 0.383
P = 0.563
P =0.769
Provisional
Tryton
Target Vessel Failure (TVF)
Side Branch ≥ 2.25 mm
Provisional N=143 Tryton N=146
TVF Diff (95% CI) = -4.3%(-12.9,4.4%)
Non Hierarchical
(22/141) (16/141) (17/141) (13/141) (6/139) (5/141)
Δ (Total Study Cohort) = 5.5%
Généreux et al. Catheter Cardiovasc Interv. 2015

17. 40.6
32.1
30.4
22.2
0
5
10
15
20
25
30
35
40
45
SB % Diameter Stenosis SB Binary Restenosis
Provisional
Tryton
P = 0.004
P = 0.26
Angiographic Outcomes (QCA)
Side Branch ≥ 2.25 mm 9 Months
Provisional N=81
Tryton N=64
%
Généreux et al. Catheter Cardiovasc Interv. 2015

18. 10.3
15.6
9.2
12.1
21.7
11.3
19.2
9.2
5.5 4.33.1 3.5
0
5
10
15
20
25
30
35
<2.25 mm ≥2.25 mm <2.25 mm ≥2.25 mm <2.25 mm ≥2.25 mm
Provisional TRYTON StentEventRate(%)
44/20320/195 22/141 18/195 17/141 6/195 6/13916/141 39/203 13/141 11/201 5/141
Side Branch Size
TVF
OR =2.42
[1.37,4.28]
OR =0.69
[0.35,1.38]
P for interaction=0.006
Target Vessel MI
OR =2.34
[1.29,4.25]
OR =0.74
[0.35,1.59]
P for interaction=0.02
Clinically Driven TVR
OR =1.82
[0.66,5.03] OR =0.81
[0.24,2.73]
P for interaction=0.32
Généreux et al. Catheter Cardiovasc Interv. 2015

19. TRYTON Confirmatory Study

20. TRYTON Confirmatory Study
Rationale
• To prospectively confirm the safety
(periprocedural MI) of the TRYTON
dedicated bifurcation stent in the
treatment of true bifurcation lesions
involving large side branches (≥2.25mm
by QCA analysis)

21. TRYTON Confirmatory Study
Angiographic Inclusion Criteria: No Change
• Single de novo “true” bifurcation lesion
• Native coronary artery
• Medina 1.1.1, 1.0.1, or 0.1.1 by visual
estimation
• Symptoms or objective evidence of
ischemia
• Vessel diameter:
• Main branch: ≥ 2.5 mm and ≤ 4.0 mm;
• Side branch: ≥ 2.5 mm and ≤ 3.5 mm
• Lesion length:
• Main vessel ≤ 28 mm; Side branch ≤ 5 mm

22. TRYTON Confirmatory Study
Performance Goal: Sample Size Calculation
• Powered Endpoint:
• Peri-procedural MI 3x CK-MB @48hrs
• Observed Rate in IDE provisional: 11.9%
• Power: 90%
• Delta: 6.0%
• 1-sided 95% upper confidence bound
• Performance Goal: 17.9%
• N = 133
• Anticipated 4% lost of follow-up
• CK-MB missing, RVD <2.25mm

23. TRYTON Confirmatory Study:
Study Recruitment
28 Investigational Centers
US =13, OUS =15
12 months enrolment

24. Baseline Characteristics: Demographic
Confirmatory Study Randomized IDE ≥2.25mm
TRYTON
(N=133)
TRYTON
(N=146)
Provisional
(N=143)
Age (years) 65.6±9.5 64.5±10.7 65.2±9.2
Male 69.9% 79.5% 81.8%
MI 32.3% 29.7% 40.4%
PCI 39.8% 37.0% 43.4%
CABG 2.3% 3.4% 3.5%
TIA / CVA 6.8% 8.9% 5.7%
CHF 6.0% 1.4% 0.0%
Diabetes Mellitus 25.8% 25.3% 28.7%
Hypertension * 82 %* 68.5% * 76.8%
Hypercholesterolemia 71.2% 72.2% 77.0%
Current Smoking 21.1% 17.1% 15.5%
Atrial Fibrillation 7.5% 12.3% 8.4%
* P<0.05

25. Medina Classification: Angio Core
Laboratory Confirmation
T: 0%
P: 2.8%
Con: 0%
“True”
Bifurcation
T: 88.3%
P: 86.8%
Con: 100%
T: 45.9%
P: 39.9%
Con: 50.4%
T: 16.4%
P: 16.8%
Con: 15.0%
T: 26.0%
P: 30.1%
Con: 34.6%
T: 2.1%
P: 5.6%
Con: 0%
T: 4.1%
P: 2.8%
Con: 0%
T: 5.5%
P: 2.1%
Con: 0%
P=Provisional T=Tryton Con=Confirmatory

26. Baseline Characteristics: Side Branch
Confirmatory Study Randomized trial ≥2.25mm
TRYTON
(N=133)
TRYTON
(N=146)
Provisional
(N=143)
Vessel Location
LAD 75.2% 72.6% 65.0%
LCX 21.1% 18.5% 25.9%
RCA 3.8% 8.9% 9.1%
Lesion Location
Ostial 98.5% 96.6% 95.8%
Proximal 1.5% 2.7% 2.8%
Mid 0.0% 0.0% 0.0%
Distal 0.0% 0.7% 1.4%
RVD (mm) 2.49±0.20 2.53±0.23 2.52±0.22
Lesion Length (mm) 5.94±2.53 4.80±1.24 4.60±0.86
Morphology
angulation ≥45o 18.0% 12.3% 24.5%
thrombus 0.9% 0.0% 0.0%
calcification – mod/severe 9.8% 5.5% 5.6%
TIMI Flow (baseline) < 3 8.2% 4.1% 4.2%

27. TRYTON Confirmatory Study: Acute
Angiographic Result
Confirmatory Study Randomized Trial ≥2.25mm
TRYTON
(N=133)
TRYTON
(N=146)
Provisional
(N=143)
Main Vessel (mm)
Acute gain
In-stent 1.81±0.47 1.77±0.46 1.78±0.40
In-segment 1.49±0.48 1.38±0.46 1.45±0.44
Side Branch (mm)
Acute gain
In-stent 1.58±0.43 1.53±0.36 na
In-segment 1.37±0.41* 1.26±0.36 0.59±0.48*
* p<0.001

28. TRYTON Confirmatory Study:
Acute Success
Confirmatory Study
Randomized Trial
≥2.25mm
Acute Success(%)
TRYTON
(N=133)
TRYTON
(N=146)
Provisional
(N=143)
Procedure Success
Achievement of final in-stent
diameter <50% in SB with assigned
study device
89.3%*
(117/131)
87.4%
(125/143)
66.9%*
(95/142)
Device Success
Achievement of final in-stent residual
stenosis <30% (by QCA) in SB using
the assigned study device without
malfunction
93.8%*
(122/130)
94.4%
(135/143)
35.9%*
(51/142)
Lesion Success
Achievement of final in-stent
diameter of <50% (by QCA) within
the side branch
100%*
(133/133)
100%
(141/141)
84.5%*
(120/142)
* p<0.001

29. TRYTON Confirmatory Study:
Resources Utilization
Confirmatory Study
Randomized Trial
≥2.25mm
TRYTON
(N=133)
TRYTON
(N=146)
Provisional
(N=143)
Procedure Time (min) 64.6±26.2 68.7±30.7 55.9±27.3
Fluoroscopy Time (min) 23.3±11.4* 24.0±13.8 11.6±5.4
Contrast Used (ml) 248.2±85.6 269.2±98.3 227±88.7
*p <0.001
~10 min more and ~30 ml more contrast

30. TRYTON Confirmatory Study:
Additional Stents (Site Reported)
2.2% (3/133)
1.5% (2/133)
Dissection: 2
Lesion Coverage: 0
Dissection: 1
Lesion Coverage: 2
Dissection: 1
Lesion Coverage: 3

31. TRYTON Confirmatory Study:
Peri-Procedural MI 3x ULN CK-MB
16/143 14/133
%
Performance Goal: 17.9%
Primary Endpoint Met
Error bars represent 1-sided 95% CI
Pivotal Provisional
≥2.25mm
Confirmatory Study
11.2% 10.5%
16/143 14/133

32. TRYTON Confirmatory Study:
Peri-Procedural MI 5x ULN CKMB
Pivotal Provisional
≥2.25mm
Confirmatory Study
6.8%
5.4%
7/103 7/130
%

33. TRYTON Confirmatory Study:
Procedural and 30-day Follow-up
Confirmatory Study Randomized Trial ≥2.25mm
Endpoints (%)
TRYTON
(N=133)
TRYTON
(N=146)
Provisional
(N=143)
Death
Procedural 0% (0.0) 0% (0.0) 0% (0.0)
30 day 0% (0.0) 0% (0.0) 0% (0.0)
Myocardial Infarction
Procedural (3x CKMB) 10.5% (14/133) 9.2% (13/141) 12.1% (17/141)
Procedural (5x CKMB) 4.5% (7/133) 3.4% (4/118) 6.8% (7/103)
30 day 10.8% (14/130)* 8.2% (12/146) 11.9% (17/143)*
Stent Thrombosis 0% (0.0) 0.7% (1/146) 0.0% (0/143)
* 2 patients in Confirmatory study have not completed 30 day follow-up at datalock and 1 patient withdrew at 30 days

34. TRYTON Confirmatory Study
Conclusions
• The TRYTON Confirmatory Study,
assessing the safety of the TRYTON stent
in the treatment of bifurcation involving
large side branches, met its primary
endpoint (performance goal) related to
peri-procedural MI
• This finding confirms the safety and
efficacy of the TRYTON dedicated
bifurcation stent in the treatment of
bifurcation involving large sides branches

35. TRYTON Confirmatory Study
Conclusions
• In light of the higher procedural success rate,
improved acute angiographic result, and
higher rate of side branch patency at 9-month
follow-up compared to provisional stenting,
the TRYTON Confirmatory Study and the
TRYTON IDE trial support the use of the
dedicated bifurcation TRYTON stent in
conjunction with standard DES in the
treatment of bifurcation lesions involving
large side branches

36. Thank You