Transcript The Detrimental Impact of Chronic Renal Insufficiency

Disclosures
Study Sponsored by ATRIUM Medical
Corporation
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
• Intracoronary administration of
antithrombotic agents, such as
Abciximab improves outcome
in patients undergoing
angioplasty.
• 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.
•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.
ClearWay RX Design
•
Atraumatic design




The balloon is semi-compliant
Inflates and infuses fluid at low pressures (14Atm)
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.)
No damage to IEL
•
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
SEM image of ePTFE microstructure –
nodes and fibrils.
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
Containment of the treatment zone
provides extended residence time to
help local drug bioavailability,
concentration and dose
Controlled infusion at 1-4 ATM throughout the entire
length of the targeted treatment zone provides
increased residence time and uptake
Infusion
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)
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.
Local drug infusion with Clearway catheters, sized to the luminal area,
assessed by OCT
Study Procedures
OCT assessment with
Goodman.
LightLab system,
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.
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 crosssection 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.
Start
Start
\\\
START
START
REF
PRE
REF
POST
PRE
Total score: 22
0
2
3
1
3
1
3
3
3
3
0
0
POST
Total score: 16
0
3
1
0
3
1
3
1
0
1
3
0
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
Frame Match
Area 4.70
Area 2.30
Area 2.51
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.
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.
Rome Heart Research
Validated Independent Core Lab
QCA and OCT analyses
Softwares
MEDIS for QCA
 Dedicated Light Lab off line
review station
Rome Heart Research
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
Only Clearway Catheter with a diam of 1,5 mm and 2,0 mm diam. used
Demographic data
Clearway
Inf
N 20
Age (years)
Males
STEMI
LAD treated
64 ± 15
65%
9 (45%)
10 (50%)
Guid. Cath.
Inf
N 21
P
62 ± 13
67%
7 (33%)
9 (43%)
NS
NS
NS
NS
Vessel treated
N 41
N 20
N 21
Basal Angiographic Measurements
Clearway
Inf
MLD (mm)
Ref. Diam (mm)
% DS
TIMI
NS
cTFC
NS
MBG
0.57 ± 0.38
2.55 ± 0.52
78.7 ± 11.5
2.16 ± 0.69
22.7 ± 22.1
2.00 ± 0.97
Guid. Cath.
Inf.
P
0.61 ± 0.33
NS
2.49 ± 0.42
NS
75.2 ± 13.5
NS
2.39 ± 0.61
23.8 ± 15.5
2.00 ± 0.84
NS
Basal Thrombus Score
P=0,28
FINAL QCA measurements
Clearway
Inf
MLD (mm)
Ref. Diam (mm)
% DS
2.64 ± 0.34
2.82 ± 0.40
5.94 ± 3.27
Guid. Cath.
Inf.
2.49 ± 0.38
2.82 ± 0.37
11.21 ± 9.07
P
NS
NS
0.022
Final TIMI flow
N 20
N 21
9,90
10,15
P=0.049
N 20
N 21
Final cTFC
0,43
Final MBG
P=0.24
0,63
N 20
N 21
Basal and FU Thrombus score
p= 0,001
p=0.0007
p= 0.38
Thrombus score change
40
37,9
35
30
33,8%
P=0.002
25
20
15
10
4,25
5
3,9%
0
Clearway Inf.
Guid. Cath. Inf.
Conclusions
Administration of abciximab by local intracoronary
infusion through the Clearway Catheter can reduce
thrombus
burden
and
improves
coronary
microcirculation.