1. 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 / ACCi Late Breaking Trial April 2nd Chicago, IL

2. Presenter Disclosure Information
ECLIPSE Trial: Ensure’s Vascular Closure Device Speeds Hemostasis
The following relationships exist related to this presentation:
S. Chiu Wong MD Consultant Cordis Modest Level
James Hermiller Speakers Bureau Cordis Modest Level
Dennis Donohoe Employee Cordis
Herbert Hutman Employee Cordis
William Bachinsky No relationships to disclose
Patrick Cambier No relationships to disclose
Robert Stoler No relationships to disclose
Janah Aji No relationships to disclose
Jason Rogers No relationships to disclose
Ravi Nair No relationships to disclose 2

3. 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 3

4. 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

5. ECLIPSE Trial Eclipse® Closure Device
The investigational ExoSeal device (Cordis, Miami FL) is a novel 3rd generation 6 Fr. extra-vascular 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.

6. 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

7. ECLIPSE Trial Pre-clinical Murine Gluteal Model: Evaluate Absorption & Tissue Reaction
No adverse tissue reaction to plugs at 14, 30 or 60 days post-implantation
The PGA Plugs were almost completely absorbed at 60 days
3-day
7-day
14-day
30-day
60-day
90-day

8. 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

9. 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

10. 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 10

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. ECLIPSE Trial Study Enrollment
Investigational Site
Study Investigator
Randomized
Roll-in
Total
Pinnacle Health at Harrisburg
William Bachinsky, MD 65 7 72
New York Presbyterian Hospital
S. Chiu Wong, MD 51 6 57
Morton Plant Hospital
Patrick Cambier, MD 45 5 50
Baylor Research Institute
Robert Stoler, MD 39
Cooper Health Systems
Janah Aji, MD 35 8 43
UC Davis Medical Center
Jason Rogers, MD 32 38
Heart Center of Indiana
James Hermiller, MD 26 4 30
University Hospitals of Cleveland
Ravi Nair, MD 23 29
Wake Heart Research
Lee Jobe, MD 18 3 21
LDS Hospitals
Peter Casterella, MD 15 20
Barnes-Jewish Hospital
John Lasala, MD, PhD 14
Sutter memorial Hospital
David Roberts, MD 13 17
St. Joseph’s Hospital Health Center
Mike Fischi, MD 9
Hahnemann Hospital
Daniel McCormick, DO 10
Mayo Clinic Hospital
John Sweeny, MD
Stanford University Medical Center
Alan Yeung, MD
Swedish Medical Center
Paul Huang , MD 2

18. 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

19. ExoSeal® 6F VCD (17 U.S. Sites) N = 488 Manual Compression (n=134)
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%)
Withdrawn N = 6 (4.5%)
30-day FU N=259 ( 97.0%)
30-day FU N=128 (95.5%)

20. ECLIPSE Trial Baseline Demographics
Roll-in (N=87)
ExoSeal® (N=267)
MC (N=134)
p-value
Mean Age (years)
63.3 ± 11.61
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 20

21. ECLIPSE Trial Procedural Characteristics
Roll-in (N=87)
ExoSeal® (N=267)
MC (N=134)
p-value
Type of Procedure (%) Diagnostic Interventional
0.9158
Type of Catheterization(%) Cardiac Peripheral
0.2351
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

22. 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
89.1% -
TTH (min.)
4.68  19.4
4.38  11.6
20.05  22.5
<0.0001
TTA (hr.)
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
1.01  2.12
1° Endpoint
P-values are based on the comparison of the two randomized cohorts

23. Manual Compression (N=134)
ECLIPSE Trial Time to Hemostasis: Randomized Patients
ExoSeal® (N=267)
Manual Compression (N=134)
P=0.0080
P=0.1430 23

24. ECLIPSE Trial TTH & TTA: Patients Receiving GP IIb/IIIa During Procedure24

25. ECLIPSE Trial Results: Primary 30-Day Safety Endpoints
Roll-in (N=87)
ExoSeal® (N=266)
MC (N=134)
Composite Major Adverse Event
0.0%
Vascular Repair
Access Site Related Bleeding Requiring Transfusion
Access Site Related Infection Requiring Treatment
Any New Documented Ipsilateral Lower Extremity Ischemia
Surgery for Access Site-Related Nerve Injury
zero!

26. ECLIPSE Trial Results: Secondary Safety Endpoints
Roll-in (N=87)
ExoSeal® (N=266)
MC (N=134)
p- value
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
1.9% (5)
0.6683
Transient access site-related nerve injury
0.0% (0)
Retroperitoneal bleeding
0.8% (2)
0.5533
Ecchymosis  6cm
0.3350
Decrease in pedal pulse
0.0% (1) --
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

27. 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

28. 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.

29. Treatment of Calcified Lesion
Thank You !!!

30. Back-up Slides

31. ECLIPSE Trial Patients with Retroperitoneal Bleeding
Retroperitoneal bleed in 2 patients (0.8%) in randomized VCD arm
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
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
Length of Hospital stay 5/22/07 - 5/26/07 31

32. ECLIPSE Trial Time to Discharge: Diagnostic vs. Interventional

33. ECLIPSE Trial Patient Disposition
Roll-in (N=87)
ExoSeal® (N=267)
MC (N=134)
Treated
Randomized (ITT) --
267/267 (100.0%)
134/134 (100.0%)
Per Protocol
233/267 (87.3%)
115/134 (85.8%)
Safety Population
87/87 (100.0%)
266/267 (99.6%)
Completed Study
83/87 (95.4%)
259/267 (97.0%)
128/134 (95.5%)
Withdrew from Treatment
4/87 (4.6%)
8/267 (3.0%)
6/134 (4.5%)
Reasons for Early Withdrawal
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
Other 33

34. ECLIPSE Trial Device / Procedural Failures with ExoSeal®
Site
Patient
Randomized Treatment
Time to Hemostasis
Hemostasis Achieved
MAEs
025
003
Roll-in 7
Yes No
004 10
035
002 21
266
011
VCD 5
031 9
401
026 11
095
009 12
039
419 14
022 15
196
010 20
417
036
416
028 23 25
280 30
012
042 34
Procedural failures were due to failure to achieve hemostasis by assigned method

35. 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
90.5%
Deploy delivery system, inject the precursor and achieve hemostasis
97.9%
StarClose
94.1%
Hemostasis using StarClose or adjunctive compression in 5 minutes, and freedom from major vascular complications
100%
Hemostasis using any method and freedom from major vascular complications

36. Other Vascular Closure Devices Published TTH and TTA
Vascular Closure Device (VCD) N
TTH (min)
TTA (hrs)
Major Complications
Minor Complications
VCD MC
Angiolink (6 Fr.) 50
5.9
21.2
3.1
6.3
0.0%
5.3%
9.7%
15.8%
Angioseal
100
2.0
10.6 NA
12%
14%
Duett
630
7.0
20.0
5.1
11.8
3.6%
1.7%
Sponge
141
8.2
14.1
2.7
7.1
5.9%
8.9%
Mynx non-randomized
190
1.3
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.

37. Manual Compression (N=134)
ECLIPSE Trial Time to Ambulation: Randomized Patients
ExoSeal® (N=267)
Manual Compression (N=134)
P=0.0021
P=0.7299 37

38. ECLIPSE Trial Time to Discharge: Diagnostic vs. Interventional