Transcript Exoseal

ECLIPSE Trial: Ensure’s Vascular
Closure Device Speeds Hemostasis
S. Chiu Wong MD
Director, Cardiac Catheterization Laboratories
New York Presbyterian Hosp.- Cornell Campus
Professor of Medicine
Weill Medical College of Cornell University
SCAI / ACCi2 2008 Late Breaking Trial
April 2nd Chicago, IL
Presenter Disclosure Information
ECLIPSE Trial: Ensure’s Vascular Closure Device Speeds Hemostasis
The following relationships exist related to this presentation:
S. Chiu Wong MD
James Hermiller
Dennis Donohoe
Herbert Hutman
William Bachinsky
Patrick Cambier
Robert Stoler
Janah Aji
Jason Rogers
Ravi Nair
Consultant
Cordis
Speakers Bureau Cordis
Employee
Cordis
Employee
Cordis
No relationships to disclose
No relationships to disclose
No relationships to disclose
No relationships to disclose
No relationships to disclose
No relationships to disclose
Modest Level
Modest Level
ECLIPSE Trial
Background (1)
• In 2007, it has been estimated that ~6 million
interventional and diagnostic procedures (cardiac
& Peripheral) were performed in the U.S.with
90% via the femoral approach
• The currently approved femoral closure devices
account for about 33% of access site closures
following these percutaneous invasive procedures
ECLIPSE Trial
Background (2)
• Although most of the currently available
access site closures devices have
demonstrated reduced time to ambulation
and hemostasis with similar complication
rates compared to manual compression, the
adoption rate is relatively low due to
limitations associated with these devices
ECLIPSE Trial
Eclipse® Closure Device
• The investigational ExoSeal
device (Cordis, Miami FL) is a
novel 3rd generation 6 Fr. extravascular closure device with an
unique deployment mechanism
that delivers a poly-glycolic acid
(PGA) “felt-like” plug atop the
femoral artery anchored by the
neuro-vascular bundle sheath.
ECLIPSE Trial
Degradation of PGA
• The PGA plug
undergoes
hydrolysis in the
body and is
degraded into CO2
and H2O via the
Kreb Cycle over a
3-month period
ECLIPSE Trial
Pre-clinical Murine Gluteal Model: Evaluate Absorption & Tissue Reaction
3-day
7-day
14-day
30-day
60-day
90-day
• No adverse
tissue reaction to
plugs at 14, 30
or 60 days postimplantation
• The PGA Plugs
were almost
completely
absorbed at 60
days
ECLIPSE Trial
ECLIPSE Trial Design
• U.S. multicenter pivotal study comparing
ExoSeal and manual compression with
2:1 randomization to assess the safety and
efficacy of ExoSeal in patients
undergoing 6Fr. diagnostic and
interventional procedures in the coronary
and peripheral vasculatures
ECLIPSE Trial
Objectives
• Two primary effectiveness endpoints to be tested for
superiority:
– Time to hemostasis (TTH)
– Time to ambulation (TTA)
• Primary safety endpoint to be tested for non-inferiority:
– 30-day combined rate of access site related
complications including bleeding, infection,
ischemia or injury requiring medical or surgical
treatment
ECLIPSE Trial
Sample Size Justification (1)
• A minimum sample size of 390 randomized
patients (260 VCD patients and 130 MC patients)
is required to:
– Detect a 5 minute reduction in mean TTH for
VCD vs. MC with over 90% power and a 5%
two-sided (2.5% one-sided) type I error
– Detect a 2-hour reduction in mean TTA for
VCD vs. MC with over 90% power and a 5%
two-sided (2.5% one-sided) type I error
ECLIPSE Trial
Sample Size Justification (2)
– Rule out ≥ 4% disadvantage for VCD vs.
MC in the incidence of major
complications using a 95% upper
confidence bound with 80% power and a
5% one-sided type I error
– In order to ensure that a minimum of 390
patients enrolled into the trial with
complete follow-up, a total of 400 patients
study was proposed
ECLIPSE Trial
Key Inclusion Criteria
• Age between 18 and 85 years
• Ability to undergo emergent vascular surgery
if complication relates to VCD or MC occurs.
• Placement of a 6F arterial sheath in the
common femoral artery
• Target vessel lumen diameter  5mm
ECLIPSE Trial
Key Exclusion Criteria
• Uncontrolled HTN at time of sheath removal (BP 
180/110mmHg)
• BMI > 40 kg/m2
• Prior femoral vascular surgery or vascular graft
• Planned repeat arterial access at closure site  30 days
post procedure
• Previous target femoral artery closure  30 days
• Calcium or atherosclerostic plaque  1 cm from the
puncture site
ECLIPSE Trial
Study Definitions
• Time to Hemostasis (TTH):
– Time to achieve no or minimal subcutaneous oozing and
absence of expanding or developing hematoma following
sheath removal
• Time to Ambulation (TTA):
– Time from sheath removal to patient able to stand and walk
at least 10 meters without re-bleed
• Time to Eligibility for Hospital Discharge:·
– Time of the access site closure to the time when patient is
eligible for discharge as per the judgment of the treating
physician
• Time to Discharge:
– Time of access site closure to time of patient actually being
discharged
ECLIPSE Trial
Study Definitions
• Device Success:
– Successful deployment of PGA plug, removal of
intact delivery system, and hemostasis achieved 
5 minutes
• Procedural Success:
– Initial hemostasis achieved by assigned method with
none of the primary safety endpoint related major
adverse events on day of procedure and at 30 days
ECLIPSE Trial
Study Definitions
• Major Adverse Events:
– Vascular injury requiring vascular repair (via surgery,
ultrasound-guided compression, transcatheter
embolization, or stent graft)
– Access site-related bleeding requiring transfusion
– Access site-related infection requiring IV/IM antibiotics
and/or extended hospitalization
– Any new ipsilateral lower extremity ischemia
– Permanent (>30 days) nerve injury at the access site or
surgery for it
ECLIPSE Trial
Study Enrollment
Investigational Site
Pinnacle Health at Harrisburg
New York Presbyterian Hospital
Morton Plant Hospital
Baylor Research Institute
Cooper Health Systems
UC Davis Medical Center
Heart Center of Indiana
University Hospitals of Cleveland
Wake Heart Research
LDS Hospitals
Barnes-Jewish Hospital
Sutter memorial Hospital
St. Joseph’s Hospital Health Center
Hahnemann Hospital
Mayo Clinic Hospital
Stanford University Medical Center
Swedish Medical Center
Study Investigator
William Bachinsky, MD
S. Chiu Wong, MD
Patrick Cambier, MD
Robert Stoler, MD
Janah Aji, MD
Jason Rogers, MD
James Hermiller, MD
Ravi Nair, MD
Lee Jobe, MD
Peter Casterella, MD
John Lasala, MD, PhD
David Roberts, MD
Mike Fischi, MD
Daniel McCormick, DO
John Sweeny, MD
Alan Yeung, MD
Paul Huang , MD
Randomized
65
51
45
39
35
32
26
23
18
15
14
13
9
6
4
3
3
Roll-in
7
6
5
6
8
6
4
6
3
5
6
4
6
4
5
4
2
Total
72
57
50
45
43
38
30
29
21
20
20
17
15
10
9
7
5
ECLIPSE Trial
Deployment Procedure
Insert device into sheath to
level of black marker band
Retract sheath checking for
pulsatile flow
Retract while compressing
green cowling to secure
Retract sheath & device
until non-pulsatile flow
Indicator window changes to black,
depress plug deployment button
Remove ExoSeal® device
and sheath
ECLIPSE Trial
Patient Enrollment
ExoSeal® 6F VCD
(17 U.S. Sites)
N = 488
Withdrawn
N = 4 (4.6%)
Roll-in
N = 87
Randomized
N = 401
30 day FU
N = 83
(95.4%)
ExoSeal® (N=267)
Manual Compression (n=134)
Withdrawn
N = 8 (3.0%)
30-day FU N=259 ( 97.0%)
Withdrawn
N = 6 (4.5%)
30-day FU N=128 (95.5%)
ECLIPSE Trial
Baseline Demographics
Roll-in
(N=87)
Mean Age (years)
63.3 ± 11.61
ExoSeal®
(N=267)
MC
(N=134)
pvalue
63.3 ± 11.13 61.4 ± 10.47 0.0896
Female (%)
33.3
31.8
38.1
0.2206
Diabetes Mellitus (%)
24.1
25.5
32.8
0.1265
Renal Insufficiency (%)
8.1
8.6
6.7
0.5636
Body Mass Index (kg/m2)
29.7 ± 4.64
28.9 ± 4.99
29.5 ± 5.40
0.4445
Baseline Hematocrit (%)
40.4
41.4
40.5
0.1654
GP IIb/IIIa Use Pre and/or
During Procedure (%)
13.8
14.2
11.2
0.4379
P-values are based on the comparison of the two randomized cohorts
ECLIPSE Trial
Procedural Characteristics
Roll-in
(N=87)
Type of Procedure (%)
Diagnostic
Interventional
Type of Catheterization(%)
Cardiac
Peripheral
ExoSeal®
(N=267)
MC
(N=134)
p-value
0.9158
66.7
33.3
50.2
49.8
49.3
50.8
0.2351
92.0
8.1
91.0
9.0
94.8
5.2
ACT Level (seconds)
Prior to Sheath Removal
168.4 ± 54.79 181.3 ± 56.01 142.1 ± 33.94 <0.0001
P-values are based on the comparison of the two randomized cohorts
ECLIPSE Trial
Results: Primary Effectiveness Endpoints
Roll-in
(N=87)
ExoSeal®
(N=267)
MC
(N=134)
p-value
Procedure Success
95.4%
91.8%
91.0%
0.8500
Device Success
95.4%
89.1%
-
-
4.68  19.4
4.38  11.6
20.05  22.5 <0.0001
1° Endpoint
1.98  2.59
2.54  5.02
6.24  13.34
0.0028
TT Eligibility for Hospital
Discharge (hr.)
9.72  14.2
12.57  13.9 16.26  27.5
0.1540
TT Hospital Discharge (hr.)
13.64  18.5 16.77  19.8 19.35  29.2
0.3612
TT Device Deployment (min.)
0.94  1.13
TTH (min.)
TTA (hr.)
1.01  2.12
P-values are based on the comparison of the two randomized cohorts
-
-
ECLIPSE Trial
Time to Hemostasis: Randomized Patients
ExoSeal® (N=267)
Manual Compression (N=134)
P=0.0080
P=0.1430
ECLIPSE Trial
TTH & TTA: Patients Receiving GP IIb/IIIa During Procedure
P=0.0220
P=0.0125
ECLIPSE Trial
Results: Primary 30-Day Safety Endpoints
Roll-in
(N=87)
ExoSeal®
(N=266)
MC
(N=134)
Composite Major Adverse Event
0.0%
0.0%
0.0%
Vascular Repair
0.0%
0.0%
0.0%
Access Site Related Bleeding
Requiring Transfusion
0.0%
0.0%
0.0%
Access Site Related Infection
Requiring Treatment
0.0%
0.0%
0.0%
Any New Documented Ipsilateral
Lower Extremity Ischemia
0.0%
0.0%
0.0%
Surgery for Access Site-Related
Nerve Injury
0.0%
0.0%
0.0%
ECLIPSE Trial
Results: Secondary Safety Endpoints
Roll-in
(N=87)
ExoSeal®
(N=266)
MC
(N=134)
pvalue
Rebleeding following initial hemostasis
3.4% (3)
5.3% (14)
2.2% (3)
0.1953
Access site related bleeding requiring
>30 min. for hemostasis
1.1% (1)
0.4% (1)
0.7% (1)
1.0000
Access site hematoma  6cm
3.4% (3)
1.9% (5)
0.7% (1)
0.6683
Transient access site-related nerve injury
0.0% (0)
0.4% (1)
0.0% (0)
1.0000
Retroperitoneal bleeding
0.0% (0)
0.8% (2)
0.0% (0)
0.5533
Ecchymosis  6cm
1.1% (1)
0.0% (0)
0.7% (1)
Decrease in pedal pulse
1.1% (1)
0.0% (0)
0.0% (1)
0.3350
--
No incidence of pseudoaneurysm not requiring treatment; treated pseudoaneurysm;
documented AV fistula; post-hospital discharge access site related bleeding; ipsilateral lower
extremity arterial emboli; transient loss of ipsilateral lower extremity pulse; ipsilateral DVT;
access site related vessel laceration; access site wound dehiscence; treated, localized access site
infection; ipsilateral peripheral artery total occlusion; intraluminal plug delivery not requiring
surgical intervention; or death.
P-values are based on the comparison of the two randomized cohorts
ECLIPSE Trial
Conclusions (1)
• In this multi-center randomized trial in pts
following 6 Fr. diagnostic/interventional
procedures, a significant reduction in the TTH and
TTA (primary effectiveness endpoints) was
achieved in pts treated with the investigational
ExoSeal device compared with MC
• Device deployment was achieved promptly in
about 1 minute on average following procedure
• There was no difference in procedural success
rates in both the ExoSeal® and MC groups
ECLIPSE Trial
Conclusions (2)
• Remarkably, there were no 30-day combined
access site related complications (primary safety
endpoint) reported in either treatment cohort
• Exoseal is non-inferior to MC in composite
major adverse event at the pre-specified 4%
margin level
• Exoseal® compares favorably to manual
compression for arteriotomy site management post
6 Fr. invasive/interventional procedures.
Treatment of Calcified Lesion
Back-up Slides
ECLIPSE Trial
Patients with Retroperitoneal Bleeding
Retroperitoneal bleed in 2 patients (0.8%) in randomized VCD arm
1) First patient (interventional / cardiac):
– Diagnosed on CT scan / leg Ultrasound normal
– No documented back pain
– Ambulation was delayed
– No transfusion given
– HCT decreased from 41.3 to 32.1 at discharge
– Length of Hospital stay 4/17/07 - 4/20/07
2) Second patient (interventional / cardiac):
– Localized swelling noted on routine groin check (Pt complaining of
right groin discomfort, no documented back pain, hypotension or
nausea)
– CT confirmed small, confined retroperitoneal bleed
– HCT decrease from 27.8 to 25.4, HCT 31.3 at discharge
– No transfusion given
– Length of Hospital stay 5/22/07 - 5/26/07
ECLIPSE Trial
35
Exoseal
MC
30
P=0.9460
25
20.5 20.6
20
P=0.1257
15
11.9
10
4.9
5
0
Time to Actual Discharge (hrs.)
Eligible for Discharge (hrs.)
Time to Discharge: Diagnostic vs. Interventional
35
Exoseal
30
MC
P=0.6720
24.8 23.7
25
P=0.2420
20
14.8
15
10
8.7
5
0
Diagnostic
Interventional
Diagnostic
Interventional
ECLIPSE Trial
Patient Disposition
Roll-in
(N=87)
ExoSeal®
(N=267)
MC
(N=134)
Randomized (ITT)
--
267/267 (100.0%)
134/134 (100.0%)
Per Protocol
--
233/267 (87.3%)
115/134 (85.8%)
87/87 (100.0%)
266/267 (99.6%)
134/134 (100.0%)
83/87 (95.4%)
259/267 (97.0%)
128/134 (95.5%)
4/87 (4.6%)
8/267 (3.0%)
6/134 (4.5%)
Withdrew Consent
1/87 (1.1%)
0/267 (0.0%)
1/134 (0.7%)
Adverse Event
0/87 (0.0%)
1/267 (0.4%)
0/134 (0.0%)
Lost to Follow-up
3/87 (3.4%)
7/267 (2.6%)
4/134 (3.0%)
Death
0/87 (0.0%)
0/267 (0.0%)
0/134 (0.0%)
Other
0/87 (0.0%)
0/267 (0.0%)
1/134 (0.7%)
Treated
Safety Population
Completed Study
Withdrew from Treatment
Reasons for Early Withdrawal
ECLIPSE Trial
Device / Procedural Failures with ExoSeal®
Site
Patient
Randomized
Treatment
Time to Hemostasis
Hemostasis
Achieved
MAEs
025
025
035
266
025
401
095
266
419
266
196
417
003
004
002
011
031
026
009
039
009
022
010
036
Roll-in
Roll-in
Roll-in
VCD
VCD
VCD
VCD
VCD
VCD
VCD
VCD
VCD
7
10
21
5
9
11
12
12
14
15
20
20
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
No
No
No
No
No
No
No
No
No
416
028
VCD
23
Yes
No
025
009
VCD
25
Yes
No
416
026
VCD
25
Yes
No
280
022
VCD
30
Yes
No
417
012
VCD
30
Yes
No
416
042
VCD
34
Yes
No
Procedural failures were due to failure to achieve hemostasis by assigned method
Other Vascular Closure Devices
Definitions of Procedural & Device Success
Mynx
Device Success
93.2% Deploy delivery system, deliver the sealant and
achieve hemostasis
Procedure Success
99.5% Hemostasis using any method with freedom from
major complications
MATRIX
Device Success
90.5% Deploy delivery system, inject the precursor and
achieve hemostasis
Procedure Success
97.9% Hemostasis using any method with freedom from
major complications
StarClose
Device Success
Hemostasis using StarClose or adjunctive
94.1% compression in 5 minutes, and freedom from major
vascular complications
Procedure Success
100%
Hemostasis using any method and freedom from
major vascular complications
Other Vascular Closure Devices
Published TTH and TTA
Vascular
Closure Device
(VCD)
N
Angiolink
TTH
(min)
TTA
(hrs)
Major
Complications
Minor
Complications
VCD
MC
VCD
MC
VCD
MC
VCD
MC
50
5.9
21.2
3.1
6.3
0.0%
5.3%
9.7%
15.8%
Angioseal
100
2.0
10.6
NA
NA
NA
NA
12%
14%
Duett
630
7.0
20.0
5.1
11.8
3.6%
1.7%
NA
NA
Sponge
141
8.2
14.1
2.7
7.1
0.0%
0.0%
5.9%
8.9%
Mynx
190
1.3
(6 Fr.)
non-randomized
2.6
0.5%
3.7%
In the randomized studies, TTH and TTA were significantly improved with VCDs as compared
with manual compression. Complication rates were not significantly different between both
treatments in any of these randomized studies.