Disclosures

1
Disclosures

• Study Sponsored by ATRIUM Medical Corporation

2
COCTAIL Study Optimal treatment of intracoronary
thrombosis with local abciximab infusion through
the ClearWay system
Sponsor ATRIUM Medical Company Principal
Investigator F Prati Investigators A. F Prati,
V Ramazzotti. S Giovanni Hosp, Rome, Italy C
Tamburino, A La Manna, D Capodanno Univ of
Catania Ferrarrotto Hosp. Italy R
Gil, T Pawlosky . Central Hospital of Internal
Affairs and Adm. Ministry (A.G.), Warsaw,
Poland. Independent Core-Lab Rome Heart
Research
Tamburino, Capodanno, et al. J Cardiovasc Med 2009
3
COCTAIL Study

• Optimal treatment of intracoronary thrombosis
  with local abciximab infusion through the
  Clearway system
• F Prati, V Ramazzotti. S Giovanni Hosp, Rome,
  Italy
• C Tamburino, A La Manna, D Capodanno Univ of
  Catania Ferrarrotto Hosp. Italy
• R Gil, T Pawlosky . Central Hospital of Internal
  Affairs and Adm. Ministry (A.G.), Warsaw, Poland.

RHR
4

• Intracoronary administration of antithrombotic
  agents, such as Abciximab improves outcome in
  patients undergoing angioplasty.

5

• The local administration of abciximab at the site
  of coronary thrombosis may enhance, by increasing
  its local concentration, the binding to both
  platelet and endothelium receptors.

6
However, even the intracoronary administration of
the drug has a major limit it does not allow an
optimal contact between plaque components and the
drug, which is rapidly washed out.
7

• The ClearWay catheter is a novel local drug
  delivery modality that promises to improve
  treatment of intracoronary thrombus due to its
  distinctive features
• It has an ultra thin micro-porous PTFE balloon
  material, capable of reducing the wash out phase,
  without injuring the vessel wall.

8
ClearWay RX Design

• Atraumatic design
• The balloon is semi-compliant
• Inflates and infuses fluid at low pressures
  (1-4Atm)
• Does not damage the Internal Elastic Lamina
• of vessel during expansion and infusion.
• Pressure at balloon surface during infusion is
  nearly Zero relative to blood pressure (when
  balloon is sized equal to vessel.)
• ePTFE balloon material
• PTFE membrane compatible with medical fluids
• Will not burst or tear during use
• Gentle weeping of fluid through spaces
• in membrane microstructure no high pressure
  jetting
• Occlusion of vessel allows site specific infusion
  
• to distal microvasculature without systemic
  dilution

No damage to IEL
SEM image of ePTFE microstructure nodes and
fibrils.
9
During inflation, drug is being infused through
the microporous balloon pores while blood flow is
occluded, maximizing drug availability without
substantial dilution by the systemic circulation.
Occlusion
Containment of the treatment zone provides
extended residence time to help local drug
bioavailability, concentration and dose
Containment
Controlled infusion at 1-4 ATM throughout the
entire length of the targeted treatment zone
provides increased residence time and uptake
Infusion
10
COCTAIL Study
Open-label trial with 50 patients randomized

• intra-coronary (from the guiding catheter)
  infusion of abciximab at the dosage of 0.25 mg/kg
  (25 patients)
• local intra-coronary infusion of abciximab
  through the ClearWay System at the dosage of
  0.25 mg/kg (25 patients)

RHR
11
COCTAIL Study
Primary objective of the study is to verify
whether administration of abciximab by local
intracoronary infusion through the Clearway
Catheter is capable of reducing thrombus burden
by OCT as compared to the modality of
intra-coronary infusion (group 1). Secondary
objective is to address whether the
administration of abciximab by local
intracoronary infusion (group 2) as compared to
the modality of intra-coronary infusion (group 1)
can improve macro- and micro-circulatory
angiographic parameters obtained post
intervention.
RHR
12
COCTAIL Study
Primary end-point Verify whether administration
of abciximab by local intracoronary infusion is
capable of reducing thrombus burden.   Secondary
end-point Post-intervention assessment of the
coronary microcirculatory function evaluated by
means of the corrected TIMI frame count flow
(cTFC) . Post-intervention assessment of the
coronary microcirculatory function, evaluated by
means of the myocardial blush grade performed
post-intervention.
13
COCTAIL Study
Local drug infusion with Clearway catheters,
sized to the luminal area, assessed by OCT
14
COCTAIL Study
Study Procedures OCT assessment with LightLab
system, Goodman. M3 OCT system (3 mm/sec speed,
20 frames/sec) M2 OCT system (2 mm/sec speed,
15,6 frames/sec) OCT wire (Imagewire) with an
outer diameter of 0.019 and longitudinal
resolution of 15 µm.
RHR
15
OCT assessment of thrombus   Application of a
score based on the semi-quantitative assessment
of thrombus (number of the involved quadrants on
the cross-sectional OCT images,) and the
longitudinal extension of the thrombus itself.
By applying this semi-quantitative grading, in
each cross-section a thrombus was classified as
absent or subtending 1, 2, 3, or 4 quadrants. The
score will be calculated as the sum of each
cross-section score.
RHR
16
REF
REF
\\\
Start
Start
START
START
PRE
POST
RHR
17
PRE
Total score 22
0
2
3
3
3
3
3
3
1
1
0
0
18
POST
Total score 16
0
0
1
1
3
3
3
3
0
1
0
1
19
Change in Lumen Diameter Post ClearWay RX
Infusion of Abciximab
Pre administration
Area 3.34
Area 3.38
Area 1.91
Area 1.28
Post administration (30 to 40 increase
luminal area)
Area 4.45
Area 4.70
Area 2.30
Area 2.51
Frame Match
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RHR
21
COCTAIL Study

• The study population
• Subjects with non ST segment elevation myocardial
  infarction scheduled for coronary angioplasty and
  with a symptom onset-to-door time less than 48
  hours
• Subjects with ST segment elevation myocardial
  infarction scheduled for coronary angioplasty and
  patent infarct related artery
• Pre-intervention baseline OCT assessment obtained
  before abiciximab administration has to confirm
  presence of significant thrombus.

RHR
22
COCTAIL Study
Sample size estimation The sample size
estimation is based on the primary efficacy
variable. Based on our assumption the mean
thrombus score value in the enrolled population
will be 287 81. The calculation of this sample
size is based on the estimation that local
infusion of abciximab by means of the Clearway
system will decrease by 30 the thrombus score,
as measured by OCT, whilst intracoronary infusion
of the same drug will decrease by 5 the
thrombus score. In order to achieve an 80
chance of detecting an absolute 25 difference
of thrombus volume between group A (intracoronary
infusion of abciximab) and group B (with local
infusion abciximab by means of the Clearway) if
this difference really exists, with a significant
level of 5, 24 patients must complete the
study.      
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Rome Heart Research Validated Independent Core
Lab QCA and OCT analyses

• Softwares
• MEDIS for QCA
• Dedicated Light Lab off line review station

RHR
Rome Heart Research
24
Pre Reopro through Clearway
RHR
Post Reopro through Clearway
25
COCTAIL Study
FINAL RESULTS

• 50 patients enrolled
• 9 were discarded due to
• wrong segments matching (N 2)
• insufficient image quality (N 6)
• Insufficient thrombus score (N1)
• 41 patients entered the final analysis
• 21 with Guiding Cath Infusion
• 20 with Clearway Infusion

RHR
Only Clearway Catheter with a diam of 1,5 mm and
2,0 mm diam. used
26
COCTAIL Study
Demographic data

• Clearway Guid. Cath. P
• Inf Inf
• N 20
  N 21
• Age (years) 64 15 62
  13 NS
• Males 65 67 NS
• STEMI 9 (45) 7 (33) NS
• LAD treated 10 (50) 9 (43)
  NS

27
COCTAIL Study
Vessel treated
N 41
N 20
N 21
RHR
28
COCTAIL Study
Basal Angiographic Measurements

• Clearway Guid. Cath.
  P
• Inf Inf.
• MLD (mm) 0.57 0.38 0.61 0.33
  NS
• Ref. Diam (mm) 2.55 0.52 2.49
  0.42 NS
• DS 78.7 11.5 75.2 13.5
  NS
• TIMI 2.16 0.69 2.39
  0.61 NS
• cTFC 22.7 22.1 23.8 15.5
  NS
• MBG 2.00 0.97 2.00 0.84
  NS

29
COCTAIL Study
Basal Thrombus Score
P0,28
RHR
30
COCTAIL Study
FINAL QCA measurements

• Clearway Guid. Cath.
  P
• Inf Inf.
• MLD (mm) 2.64 0.34 2.49 0.38
  NS
• Ref. Diam (mm) 2.82 0.40 2.82
  0.37 NS
• DS 5.94 3.27 11.21 9.07
  0.022

31
COCTAIL Study
Final TIMI flow
RHR
N 20
N 21
32
COCTAIL Study
Final cTFC
9,90
10,15
P0.049
RHR
N 20
N 21
33
COCTAIL Study
0,43
Final MBG
P0.24
0,63
RHR
N 21
N 20
34
COCTAIL Study
Basal and FU Thrombus score
p 0.38
p0.0007
p 0,001
RHR
35
COCTAIL Study
Thrombus score change
33,8
P0.002
3,9
RHR
36
COCTAIL Study
Conclusions

• Administration of abciximab by local
  intracoronary infusion through the Clearway
  Catheter can reduce thrombus burden and improves
  coronary microcirculation.