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AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
TRIAS HR Pilot Study
RCT comparing Genous EPC capturing stent
with Taxus Paclitaxel eluting stent
Robbert J de Winter MD PhD FESC
Academic Medical CenterUniversity of Amsterdam
The Netherlands
Late Breaking Clinical Trials Late Breaking Clinical Trials TCT, October 22TCT, October 22ndnd 2007, 2007, Washington, USAWashington, USA
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
Disclosures Dr. R.J. de WinterDisclosures Dr. R.J. de Winter
Grant and / or Research SupportOrbusNeich
ConsultingOrbusNeich, Merck-Sharp Dome
Speaker’s BureauLilly
c r e a t e
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AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
IntroductionIntroductionTRIAS HR Pilot studyTRIAS HR Pilot study
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
IntroductionIntroductionTRIAS HR Pilot studyTRIAS HR Pilot study
c r e a t e
��������������
• Accelerated Healing
• Protects Against Thrombus
• Minimizes Restenosis
• Improved Safety Profile Over Current
DES
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
ObjectiveObjective
To compare the feasibility and efficacy of the To compare the feasibility and efficacy of the GenousGenous EPCEPC--attracting stent with the attracting stent with the TaxusTaxuspaclitaxelpaclitaxel--eluting stent in the treatment of eluting stent in the treatment of coronary artery stenosis in patients / lesions coronary artery stenosis in patients / lesions with high risk of restenosis. with high risk of restenosis.
TRIAS HR Pilot studyTRIAS HR Pilot study
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
TRIAS HR Pilot studyTRIAS HR Pilot study
Restricted DES use in selected patients with Restricted DES use in selected patients with high risk of restenosis, BMS in patients with high risk of restenosis, BMS in patients with low risk of restenosislow risk of restenosis
High risk of restenosis is defined as:High risk of restenosis is defined as:
�� Lesion Lesion �� 23 mm in length23 mm in length�� Lesions in vessels Lesions in vessels �� 2.8 mm in diameter2.8 mm in diameter�� Any lesion in diabetic patientsAny lesion in diabetic patients�� Chronic total occlusionChronic total occlusion
DesignDesign
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
High risk of restenosisHigh risk of restenosis
Genous StentGenous Stent TaxusTaxus stentstent
Statins 1 wkStatins 1 wk
AngiographicAngiographicSub studySub study
Target vessel failureTarget vessel failure
NonNon--inferiorityinferiority
Clopidogrel 6Clopidogrel 6Clopidogrel 1 mClopidogrel 1 m
12 m clinical FU12 m clinical FU 12 m clinical FU12 m clinical FU
®®
5 y clinical FU5 y clinical FU 5 y clinical FU5 y clinical FUDeath / MIDeath / MI
SuperioritySuperiority
TRIAS HR Pilot studyTRIAS HR Pilot study
Lesion Lesion �� 23 mm23 mmRVD RVD �� 2.8mm2.8mmDiabetesDiabetesCTOCTO
DesignDesign
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
TRIAS HR Pilot studyTRIAS HR Pilot study
�� SingleSingle--center, prospective, randomized, singlecenter, prospective, randomized, single--blindblind
studystudy
�� Inclusion period: February 2006 Inclusion period: February 2006 -- April 2007April 2007
�� Patients with de novo coronary artery lesionPatients with de novo coronary artery lesion
with a high risk of restenosiswith a high risk of restenosis
�� Dual antiDual anti--platelet therapy for at least 1 month after platelet therapy for at least 1 month after
GenousGenous and 6 months after and 6 months after TaxusTaxus stentstent
�� 30 days, 6 months and 1, 2, 3, 4, 5 year clinical FU30 days, 6 months and 1, 2, 3, 4, 5 year clinical FU√√ telephone contact telephone contact
√√ clinical records and discharge lettersclinical records and discharge letters
MethodsMethods
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
TRIAS HR Pilot studyTRIAS HR Pilot study
�� Clinically stable patients undergoing a PCI for a Clinically stable patients undergoing a PCI for a
native, de novo, coronary artery native, de novo, coronary artery lesion(slesion(s))
�� Target lesion considered high risk of restenosisTarget lesion considered high risk of restenosis√√ Lesion Lesion �� 23 mm23 mm
√√ RVD RVD �� 2.8mm2.8mm
√√ DiabetesDiabetes
√√ CTOCTO
�� All patients on statin therapy All patients on statin therapy �� 7 days 7 days
Inclusion criteriaInclusion criteria
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
TRIAS HR Pilot studyTRIAS HR Pilot study�� < 18 years< 18 years
�� ST elevation myocardial infarctionST elevation myocardial infarction
�� Current unstable arrhythmiasCurrent unstable arrhythmias
�� Recipient of a heart transplant or any other organ transplant oRecipient of a heart transplant or any other organ transplant or is on a waitingr is on a waiting
list for any organ transplantlist for any organ transplant
�� Scheduled to receive chemotherapy or radiation therapy within 3Scheduled to receive chemotherapy or radiation therapy within 30 days prior or0 days prior or
after the procedureafter the procedure
�� Receiving immuneReceiving immune--suppression therapy or has known immunosuppressive or suppression therapy or has known immunosuppressive or
autoimmune disease (e.g. human immunodeficiency virus, systeautoimmune disease (e.g. human immunodeficiency virus, systemic lupus mic lupus
erythematosuserythematosus atcatc.).)
�� Hypersensitivity or contraindication to aspirin, either heparinHypersensitivity or contraindication to aspirin, either heparin or or bivalirudinbivalirudin, ,
clopidogrel, clopidogrel, paclitaxelpaclitaxel, cobalt, chromium, nickel, tungsten, acrylic and , cobalt, chromium, nickel, tungsten, acrylic and fluorofluoro--
polymers or contrast sensitivity that can not be adequately polymers or contrast sensitivity that can not be adequately prepre--medicatedmedicated
�� Planned elective surgery within the first 6 months after the prPlanned elective surgery within the first 6 months after the procedure that will ocedure that will
require discontinuing either aspirin or clopidogrelrequire discontinuing either aspirin or clopidogrel
Exclusion criteriaExclusion criteria
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
TRIAS HR Pilot studyTRIAS HR Pilot study�� Platelet count < 100,000 or > 700,000 cells/ mm3, a WBC < 3,000Platelet count < 100,000 or > 700,000 cells/ mm3, a WBC < 3,000 cells/ mm3, cells/ mm3,
or liver disease (including laboratory evidence of hepatitisor liver disease (including laboratory evidence of hepatitis))
�� Severe renal insufficiencySevere renal insufficiency
�� Coronary anatomy unsuited for coronary revascularization Coronary anatomy unsuited for coronary revascularization
�� CVA (hemorrhagic / ischemic) or TIA of any etiology within 30 dCVA (hemorrhagic / ischemic) or TIA of any etiology within 30 days of ays of
randomizationrandomization
�� Evidence of active abnormal bleeding within 30 days of randomizEvidence of active abnormal bleeding within 30 days of randomization ation
�� Severe hypertensionSevere hypertension
�� Previous participation in this study or any other trial within Previous participation in this study or any other trial within the previous 30 daysthe previous 30 days
�� Circumstances that prevent followCircumstances that prevent follow--up up
�� Women who are pregnant or who are of childbearing potential whoWomen who are pregnant or who are of childbearing potential who do not use do not use
adequate contraception. adequate contraception.
�� Criteria related to the EPCCriteria related to the EPC--attracting stent:attracting stent:
�� Patients who have previously received Patients who have previously received murinemurine therapeutic antibodies and therapeutic antibodies and
exhibited sensitization through the production of Human Antiexhibited sensitization through the production of Human Anti--MurineMurine Ab(HAMAAb(HAMA).).
Exclusion criteriaExclusion criteria
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
TRIAS HR Pilot studyTRIAS HR Pilot study
RandomizationRandomization�� Randomization target lesion between Randomization target lesion between GenousGenous stent stent
and and TaxusTaxus stentstentMultiple lesionsMultiple lesions
�� High risk lesions treated according to the randomizedHigh risk lesions treated according to the randomized
treatment assignment treatment assignment
�� Low risk of restenosis lesions in nonLow risk of restenosis lesions in non--target vessels target vessels
treated with BMStreated with BMS
Bailout procedureBailout procedure
�� Use bailoutUse bailout--stent according to randomized treatment stent according to randomized treatment
assignmentassignment
Treatment strategyTreatment strategy
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
TRIAS HR Pilot studyTRIAS HR Pilot study
Target vessel failureTarget vessel failure at 1 year:at 1 year:
�� Cardiac deathCardiac death
�� Myocardial infarction Myocardial infarction (unless documented to arise from the non(unless documented to arise from the non--treated coronary artery)treated coronary artery)
�� Repeat revascularization of the treated vesselRepeat revascularization of the treated vessel
Main long term endpoint Main long term endpoint at 5 years:at 5 years:
�� Death or MIDeath or MI
Primary endpointPrimary endpoint
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
TRIAS HR Pilot studyTRIAS HR Pilot study
�� Procedural success, defined as a less than 20% Procedural success, defined as a less than 20%
residual stenosis and TIMI 3 flow post PCIresidual stenosis and TIMI 3 flow post PCI
Within 1, 2 , 3, 4, and 5 years:Within 1, 2 , 3, 4, and 5 years:
�� Target Vessel FailureTarget Vessel Failure
�� Target Lesion FailureTarget Lesion Failure
�� Target Vessel Revascularization Target Vessel Revascularization
�� Target Lesion Revascularization Target Lesion Revascularization
�� Hospitalization for Acute Coronary SyndromeHospitalization for Acute Coronary Syndrome
Secondary endpointsSecondary endpoints
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
(98%)(98%)(96%)(96%)
(3%)(3%)(26%)(26%)(41%)(41%)
(15%)(15%)(85%)(85%)
(32%)(32%)(64%)(64%)(53%)(53%)(56%)(56%)(27%)(27%)
((74%)74%)±± 10 y10 y
NsNsNsNs
NsNsNsNsNsNs
NsNsNsNs
NsNsNsNsNsNsNsNs0.0250.025
NsNsNsNs
(100%)(100%)(95%)(95%)
(3%)(3%)(26%)(26%)(38%)(38%)
(18%)(18%)(82%)(82%)
(33)%(33)%(53%)(53%)(63%)(63%)(46%)(46%)(14%)(14%)
(73%)(73%)±± 10 y10 y
98989393
3325253737
18188080
32325252626245451414
72726262
33Previous CABGPrevious CABG2525Previous PCIPrevious PCI3939Previous MIPrevious MI
1414Unstable anginaUnstable angina8181Stable anginaStable angina
9393StatinsStatins9191AspirinAspirin
3030Current smokingCurrent smoking6161Family history of CADFamily history of CAD5050HypercholesterolemiaHypercholesterolemia5353HypertensionHypertension2626DiabetesDiabetes
Risk factorsRisk factors7070MaleMale6363AgeAge
TaxusN = 95
GenousN = 98
P-value
TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResultsBaseline characteristicsBaseline characteristics
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
(23%)(23%)(37%)(37%)((1% )1% )(39%)(39%)
(20%)(20%)
(80%)(80%)
(24(24%)%)
(42%)(42%)(42%)(42%)(12%)(12%)((2% )2% )
NsNs
0.0040.004
NsNs
NsNs
NsNs
(26%)(26%)(40%)(40%)( 1( 1%)%)(34%)(34%)
( 7( 7%)%)
(83%)(83%)
(32%)(32%)
(47%)(47%)(45%)(45%)( 8%)( 8%)( 0%)( 0%)
31314848
114141
99
101101
3939
575754541010
00
11LMLM4949RCARCA
Treated vesselTreated vessel
2525Vessels Vessels �� 2.8 mm2.8 mm
2929CXCX4646LADLAD
100100Lesions Lesions �� 23 mm23 mm
3030Total chronic occlusionTotal chronic occlusion
5252CC5252B2B21515B1B1
22AAType of lesionType of lesion
TaxusN = 125
GenousN = 121
P-value
TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResultsLesion characteristicsLesion characteristics
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
NsNs±± 101025.425.4±± 121226.826.8Lesion length, mmLesion length, mm
NsNs±± 0.50.53.23.2±± 0.30.33.23.2Ref vessel diameter, mmRef vessel diameter, mm
(99%)(99%)
±± 3.53.5
(70%)(70%)
±± 2.52.5
±± 1212
±± 0.480.48
(89(89%)%)
(66%)(66%)
NsNs
NsNs
NsNs
NsNs
NsNs
NsNs
NsNs
NsNs
(98%)(98%)
±± 3.63.6
(73%)(73%)
±± 2.62.6
±± 14.314.3
±± 0.540.54
(89%)(89%)
(61%)(61%)
119119
18.618.6
8888
1313
31.731.7
1.21.2
108108
7474
124124Procedural success Procedural success
1818Max Max AtmAtm post dilatationpost dilatation
8888Post dilatationPost dilatation
1414Max Max AtmAtm stent placementstent placement
30.730.7Total stent length, mmTotal stent length, mm
1.21.2Stents per lesionStents per lesion
111111PrePre--dilatationdilatation
8383PrePre--procedure TIMI 3 flowprocedure TIMI 3 flow
TaxusN = 125
GenousN = 121
P-value
TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResultsProcedural characteristicsProcedural characteristics
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
GenousGenous•• wirewire perforationperforation resultingresulting in in pericardial effusionpericardial effusion
•• stentstent loss in RCA, loss in RCA, afterafter dilatationdilatation TIMI 2 TIMI 2 flowflow
•• nono--reflowreflow phenomenonphenomenon; ; afterafter additionaladditional dilatationsdilatationsTIMI 3 TIMI 3 flowflow; ; maxmax CKCK--MB 145 MB 145 µµg/Lg/L
TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResultsProcedural complicationsProcedural complications
TaxusTaxus•• wire perforation resulting in pericardial effusionwire perforation resulting in pericardial effusion•• major major extravasationextravasation of contrastof contrast
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
NsNs(2.2%)(2.2%)22(1.1%)(1.1%)11Stent thrombosisStent thrombosis
(6.5%)(6.5%)
(2.2%)(2.2%)(7.6%)(7.6%)
(2.2%)(2.2%)
(1.1%)(1.1%)
(1.1%)(1.1%)
(1.1%)(1.1%)
00
11000011
11
000000
NsNs00TVR remoteTVR remote
00CABGCABG
NsNs22TLRTLR
0.050.0566Non TVR Non TVR
0.0280.02877Repeat PCIRepeat PCI
00CardiacCardiac00NonNon--CardiacCardiac
22
00
NsNsMIMI
DeathDeath
TaxusN=92
GenousN=95
P-value
TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResults3030--Day clinical outcomeDay clinical outcome
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
Genous StentGenous StentN = 95N = 95
TaxusTaxus stentstentN = 92N = 92
TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResults66--month clinical outcomemonth clinical outcome
On Clopidogrel:On Clopidogrel: 42 (44 %)42 (44 %) 68 (73 %)68 (73 %)
Anginal complaints:Anginal complaints:No anginaNo angina 74 (78 %)74 (78 %) 79 (86 %)79 (86 %)CCS 1CCS 1 7 (7.3 %)7 (7.3 %) 4 (4.3 %)4 (4.3 %)CCS 2CCS 2 11 (12 %)11 (12 %) 5 (5.4 %)5 (5.4 %)CCS 3CCS 3 2 (2.1 %)2 (2.1 %) 3 (3.3 %)3 (3.3 %)CCS 4CCS 4 1 (1.1 %)1 (1.1 %) 1 (1.1 %)1 (1.1 %)
Mean followMean follow--up @ 192 daysup @ 192 days
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
Repeat PCIRepeat PCI
(1.1%)(1.1%)
(14%)(14%)
(4.3%)(4.3%)
(3.2%)(3.2%)
(2.1%)(2.1%)
(3.2%)(3.2%)
(5.3%)(5.3%)
(1.1%)(1.1%)
22
3300
55
11
00
00TVR remoteTVR remote
NsNs11CABGCABG
NsNs44TLRTLR
0.0070.0071313Non TVR Non TVR
33
00
NsNsMIMI
DeathDeath
TaxusN=92
GenousN=95
P-value
TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResults66--month clinical outcomemonth clinical outcome
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
Repeat PCIRepeat PCI
(5.4%)(5.4%)
(1.1%)(1.1%)
(4.3%)(4.3%)
(3.2%)(3.2%)
(8.4%)(8.4%)
(2.1%)(2.1%)
(5.3%)(5.3%)
(1.1%)(1.1%)
88
22
00
55
11
00
NsNs55Target vessel failureTarget vessel failure
00TVR remoteTVR remote
NsNs11CABGCABG
NsNs44TLRTLR
33
00
NsNsMIMI
DeathDeath
TaxusN=92
GenousN=95
P-value
TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResults66--month clinical outcomemonth clinical outcome
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResults66--month clinical outcomemonth clinical outcome
Stent thrombosis:Stent thrombosis:
GenousGenous@ 6 hours @ 6 hours TLR, no MITLR, no MI
TaxusTaxus@ 24 hours@ 24 hours MI, TLRMI, TLR@ 10 days @ 10 days MI, TLRMI, TLR@ 155 days @ 155 days MI, TLRMI, TLR
�� All All angiographicallyangiographically documented stent thrombosisdocumented stent thrombosis�� All on dual All on dual antiplateletantiplatelet therapy at time of STtherapy at time of ST
AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology
Randomized study comparing the Genous stent and first generation DES is feasible in patients treated with PCI for high risk restenosis lesions
Similar clinical outcomes at 6-months in this (underpowered) pilot study in patients treated with PCI for high risk restenosis lesions between the GenousEPC-capturing stent and the Taxus paclitaxel eluting stent
The pilot study is followed by a large multi-center study
TRIAS HR Pilot studyTRIAS HR Pilot study ConclusionsConclusions
AMC Amsterdam AMC Amsterdam InterventionalInterventional CardiologyCardiology
AMC AMC GenousGenous experienceexperience
Interventional operators
K.T. Koch
J.P. Henriques
R.J. vd Schaaf
J. Baan
M.M .Vis
J.J. piek
de Winter RJ Drug eluting stent summit, TCT 2007de Winter RJ Drug eluting stent summit, TCT 2007
Data collection and statistics
J.G.P. Tijssen
M.A. Beijk
C.J. Verouden
M. Klomp
Cathlab nursing staff
M.G. Meesterman
F. Hoekstra
N. van Daalen
Research nursing staff
M. Klees
E. Schoenhagen
W. Rohling
Database manager
I. vd Wal
Project management
L. Peeters
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