... study stent for the PISCES trial. PISCES Paclitaxe

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PISCESPaclitaxel In-Stent Controlled Elution
Study

• As presented by
• Patrick W. Serruys, MD, PhD, FACC
• Principal Investigator
• Thoraxcentre - Erasmus University
• Rotterdam, The Netherlands

4 and 12-Month Results
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CoStar Stent Design
CoStar Paclitaxel-Eluting Coronary Stent System
Clinical Trials
A Stent Designed Specifically for Controlled and
Targeted Drug Delivery
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Conor Stainless Steel and Cobalt Chromium Stents
MedStent was the study stent for the PISCES
trial
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PISCES Paclitaxel In-Stent Controlled Elution
Study

• Study Purpose
• To evaluate safety and performance of the Conor
  MedStent and determine optimal dosing of
  Paclitaxel in a prospective, multi-center,
  sequentially enrolled study involving 6 different
  release formulations. The proposed intended use
  of the MedStent is to improve and maintain
  arterial lumen diameter in patients with ischemic
  heart disease in native coronary arteries with de
  novo lesions.

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PISCES TrialStudy Design Patient Follow-Up
Baseline Angiography
1 Month Clinical
4 Month Clinical
Dose Ranging Study
4 Month Angiographic with QCA IVUS
1 Year Clinical
12 Month Angiographic with QCA IVUS
Bi-Directional direction of paclitaxel
elution is both mural and luminal 12 Month
Angiography w/ QCA and IVUS was optional
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PISCES TrialStudy Endpoints
Safety Endpoint A composite of MACE at 4
months Efficacy Endpoints Late Loss by QCA
within the stent Stent Volume Obstruction by
IVUS Rate of Binary Restenosis The data is
presented as intent to treat.
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Participating Investigators Centers
62
Sao Paolo
J. E. Sousa / A. Abizaid
31
Rotterdam
P.W. Serruys
26
Breda
P. den Heijer
23
Eindhoven
H. Bonnier
12
Rotterdam Zuid
A. G. de Vries
11
New Zealand
D. McClean
10
Antwerp
S. Verheye
8
Buenos Aires
J. Belardi
7
Caracas
J. A. Condado
1
Kreuzlingen
M. Pieper
191
Total
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Risk Factors per Dose
D1 D2 D3 D4 D5 D6 Total Dose/ Duration/ Directio
n 10/5/b 10/10/m 10/10/b 10/30/m 30/30/m 30/10/b
N30 N31 N30 N31 N39 N30 N191 DM,
16 16 23 16 10 33 19 HT, 40 65 63 55 36 63 53
Dyslip, 67 65 73 65 62 67 66 Prior MI,
40 42 33 29 41 43 38 Prior PCI,
7 7 10 16 15 16 12
Release Direction b bi-directional, m mural
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PISCES TrialProcedural Data
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PISCES TrialBaseline Patient Demographics
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PISCES TrialBaseline Lesion Demographics
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QCA Analysis - Methodology
Distal
Proximal
17 mm
5 mm
5 mm
C
D
vessel
Side Branch
Side Branch
In-Stent
Peri-Stent
Total Vessel
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In-Stent Binary Restenosis at 4 Months
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In-Stent Binary Restenosis at 4 and 12
MonthsCumulative

5.6
5.6
0
0
N18
N32
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In-Stent Late Loss at 4 Months
(mm)
N38
N29
N26
N43
N28
N28
N29
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In-Stent Late Loss at 4 and 12 MonthsSerial
Analysis
Late loss of patients undergoing TLR at 4 months
(D50, D61) is imputed as the value of late
loss at 12 months.
p0.01
p0.53
0.52
(mm)
0.40
0.36
0.32
N32
N18
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Neo-Intimal Volume at 4 Months
(mm3)
N37
N26
N21
N39
N27
N23
N28
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Neo-Intimal Volume at 4 and 12 MonthsSerial
Analysis
(mm3)
p0.29
p0.0004
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14
11
9
N30
N15
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In-Stent Volume Obstruction at 4 Months

N39
N27
N23
N26
N28
N21
N37
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In-Stent Volume Obstruction at 4 and 12
MonthsSerial Analysis
p0.0004
p0.31
12

8
7
6
N15
N30
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MACE at 4 and 12 Months
20.7
17.2
16.7
13.3

10
8
6.7
6.9
6.7
5.1
3.4
2.6
N29
N39
N30
N50
N30
N29
N30
Between 4 and 12 months, 1 non Q-wave MI occurred
in D5 in a non-target vessel and 1 Q-wave MI
(total occlusion of target lesion) in D6.
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TLR at 4 and 12 Months

6.9
3.4
0
0
10/30/m
30/30/m
N50
N30
N30
N29
N30
N29
N39
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Proximal and Distal Edge Late Loss at 4 and 12
Months - Serial Analysis
D5
p0.44
p0.97
D6
p0.10
p0.69
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Conclusions

• This study represents one of the most
  comprehensive analyses of pharmacokinetic
  releases ever performed in a FIM Study.
• The safety profile of this system - using an
  erodable polymer and delivering 100 of the drug
  is within the accepted standards.
• Protocol called for 6 months Plavix therapy.
  There were no reported cases of delayed stent
  thrombosis in the interval period.
• Although the doses used were substantially less
  than paclitaxel-coated stents, the inhibition of
  neo-intimal hyperplasia was similar.

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Conclusions

• In the 2 long release (most effective)
  formulations the TLR and MACE rates remained low
  at 12 months.
• In D5, there was 0 in stent restenosis at both
  4 and 12 months and in D6 the restenosis rate
  remained 5.6.
• There was a modest but statistically significant
  increase in neo-intimal volume, in-stent
  obstruction and late loss between 4 months and 12
  months in D5 but not in D6. The TLR and
  restenosis rates in the D6 group were not as good
  as in D5.
• These 2 pharmacokinetic profiles are currently
  under investigation in the Eurostar trial with a
  thin strut cobalt chromium stent and 33 less
  polymer volume.