the tryton pivotal: randomized trial & confirmatory study | philippe généreux, m.d
TRANSCRIPT
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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
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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
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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)
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Randomized Bifurcation Stent Studies(NORDIC, BBC ONE, CACTUS)
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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
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Tryton Side Branch Stent Sizes
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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
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TRYTON Pivotal RCT
Généreux et al. J Am Coll Cardiol 2015;65:533–43
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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
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Provisional (n= 349)28 (8.0%)
Tryton (n= 355)3 (0.9%) 7 (2.0%)
Additional Side Branch Stents(Site Reported)
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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
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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
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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
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TRYTON Large SBs Sub-Analysis:Side Branches ≥2.25mm
Généreux et al. Catheter Cardiovasc Interv. 2015
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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
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%
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
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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
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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
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TRYTON Confirmatory Study
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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)
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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
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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
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TRYTON Confirmatory Study:Study Recruitment
28 Investigational CentersUS =13, OUS =15
12 months enrolment
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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
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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
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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%
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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
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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
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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
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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
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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
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TRYTON Confirmatory Study: Peri-Procedural MI 5x ULN CKMB
Pivotal Provisional ≥2.25mm
Confirmatory Study
6.8%
5.4%
7/103 7/130
%
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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
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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
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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
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Thank You