Philippe Généreux, MDfor the Tryton Bifurcation Trial Investigators

Columbia University Medical CenterCardiovascular 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

Disclosure Statement of Financial Interest

Philippe Généreux, MDWithin 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

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)

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

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

Tryton Side Branch Stent Sizes

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

TRYTON Pivotal RCT

Généreux et al. J Am Coll Cardiol 2015;65:533–43

Tryton Study Design

DES (main vessel) + Provisional side branch

Baseline Angiography – Eligible for RandomizationTrue bifurcation with SB≥ 2.5mm by visual estimation

Angiographic F/Uat 9 months

Clinical F/U at 9 months

% DS side branchn~374

Tryton side branch + DES (main vessel)

TVF Primary Endpoint

N = 704

IVUS F/Uat 9 months

IVUS Cohort n~96

Clinical F/U at 9 months

Angiographic F/Uat 9 months

IVUS F/Uat 9 months

Provisional (n= 349)28 (8.0%)

Tryton (n= 355)3 (0.9%) 7 (2.0%)

Additional Side Branch Stents(Site Reported)

TRYTON Pivotal RCT Primary Non-Inferiority Endpoint

Not Met%

TVF Cardiac Death Target Vessel MI Clinically Driven TVR

02468

101214161820

12.8

0

10.7

3.6

17.4

0

15.1

4.7

Non Hierarchical

P= 0.11P = 0.11

P =0.56

ProvisionalTryton

Généreux et al. J Am Coll Cardiol 2015;65:533–43

Series10

10

20

30

40

50

60

38.631.6

P=0.002

ProvisionalTryton

Side Branch %DS (In-segment)Secondary Endpoint

%

Secondary Superiority Endpoint MetAngiographic Cohort n=326

Généreux et al. J Am Coll Cardiol 2015;65:533–43

0 1.5 1.65 1.8 1.9

5 2.1 2.25 2.4 2.5

5 2.7 2.85 3

3.15

0

20

40

60

80

100

120

140

160

180

14

33

49

152

164

104

66 68

24

10 11 6

≥ 2.25 mm: 41% of ITT lesions

Side Branch RVD (Core Lab)#

Freq

uenc

y

Pre Procedure Side Branch Size

TRYTON Large SBs Sub-Analysis:Side Branches ≥2.25mm

Généreux et al. Catheter Cardiovasc Interv. 2015

Provisional (n= 143)8 (5.6%)

Tryton (n= 146) 1 (0.7%)

Side Branch Bail Out StentingNearly Eliminated in Tryton GroupSide Branch ≥ 2.25 mm

%

TVF Cardiac Death Target Vessel MI Clinically Driven TVR0

2

4

6

8

10

12

14

16

18

15.6

0

12.1

4.3

11.3

0

9.2

3.5

P= 0.383

P = 0.563

P =0.769

ProvisionalTryton

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

SB % Diameter Stenosis SB Binary Restenosis0

5

10

15

20

25

30

35

40

45

40.6

32.130.4

22.2

ProvisionalTryton

P = 0.004

P = 0.26

Angiographic Outcomes (QCA)Side Branch ≥ 2.25 mm 9 Months

Provisional N=81Tryton N=64

%

Généreux et al. Catheter Cardiovasc Interv. 2015

10.315.6

9.212.1

21.7

11.3

19.2

9.25.5 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 Stent E

vent

Rat

e (%

)

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

TRYTON Confirmatory Study

TRYTON Confirmatory StudyRationale

• 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)

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

TRYTON Confirmatory StudyPerformance 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

TRYTON Confirmatory Study:Study Recruitment

28 Investigational CentersUS =13, OUS =15

12 months enrolment

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±9.2Male 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

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

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±0.22Lesion Length (mm) 5.94±2.53 4.80±1.24 4.60±0.86Morphology   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%

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

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 SuccessAchievement 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

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±27.3Fluoroscopy Time (min) 23.3±11.4* 24.0±13.8 11.6±5.4Contrast Used (ml) 248.2±85.6 269.2±98.3 227±88.7

*p <0.001

~10 min more and ~30 ml more contrast

TRYTON Confirmatory Study: Additional Stents (Site Reported)

3% (4/133)

2.2% (3/133)1.5% (2/133)

Dissection: 2Lesion Coverage: 0 Dissection: 1

Lesion Coverage: 2

Dissection: 1Lesion Coverage: 3

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

TRYTON Confirmatory Study: Peri-Procedural MI 5x ULN CKMB

Pivotal Provisional ≥2.25mm

Confirmatory Study

6.8%

5.4%

7/103 7/130

%

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

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

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

Thank You