1. For the CLOSE-UP study group
Randomized Comparison of Manual Compression and Use of FemoSeal Vascular Closure Device for Closure after Femoral Artery Access Coronary Angiography
CLOSE-UP
The CLOSure dEvices Used in everyday Practice study
Niels Ramsing Holm, Birthe Sindberg, Mia Schou, Michael Maeng, Anne Kaltoft, Morten Bøttcher, Lars Romer Krusell, Leif Thuesen, Christian Juhl Terkelsen, Evald Høj Christiansen, Hans Erik Bøtker, Steen Dalby Kristensen and Jens Flensted Lassen
For the CLOSE-UP study group

2. Potential conflicts of interest
Speaker’s name: Niels R. Holm
I have the following potential conflicts of interest to report:
X Research contracts; St. Jude Medical  Consulting
 Employment in industry
 Stockholder of a healthcare company
 Owner of a healthcare company
X Other(s)
Educational grant; St. Jude Medical

3. Potential conflicts of interest
The study was supported by unrestricted research grants from Vingmed Danmark A/S and St. Jude Medical

4. CLOSE-UP: Background
Vascular Closure Devices (VCD) for femoral access CAG?
Debatable safety advantages
Superior efficacy
Cost-effectiveness?
FemoSeal VCD safe in SCAAR registry*
no randomized trial
* (2007)

5. CLOSE-UP: Aim
Compare safety and efficacy of FemoSeal and Manual Compression (MC) in a randomized trial

6. CLOSE-UP: FemoSeal Sandwich type seal discs Fully resorbable polymer
No collagen or trombosing agent
FemoSeal* by RADI (Uppsala, Sweden) at study start,
now St. Jude Medical (St. Paul, MN)
*available in select markets. Not for sale in USA.

7. CLOSE-UP: Methods Investigator initiated, driven and concluded
Randomized trial
Single high-volume center
CAG patients
No invasive diagnostics or therapy
In-hospital clinical evaluation
14 days follow-up

8. CLOSE-UP: Methods Inclusion criteria Exclusion criteria Age ≥18 CAG
Femoral access
6F sheath
Exclusion criteria
Invasive treatment
Recent CAG (within 1 month)
Haematoma before closure
INR >3.1
Thrombolysis within 24h
Pregnancy
Severe hypertention (>200/110)

9. CLOSE-UP: Treatment Best practice CAG MC
Immediate sheat removal
Compression to haemostasis (at least 5 min)
Sandbag discouraged in standard care
No bandage or compression system used in standard care
One hour bedrest recommended in both groups

10. CLOSE-UP: Endpoints Primary endpoint: Secondary endpoints:
In-hospital haematoma > 5 cm
Secondary endpoints:
14 days composite of access site major adverse vascular events (MAVE)
Pseudoaneurysm, A-V fistula, surgical repair, major bleeding, infection
14 days haematoma > 5 cm (patient self assessment)
Time to haemostasis
Time to ambulation
Device / deployment failure
Need for new manual compression

11. CLOSE-UP: Power calculation
Large haematomas were expected to occur in 11% in the MC group and 6% of patients in the FemoSeal group. With an alpha of 5% and power of 80%;
423 patients were needed in each group

12. Patients randomized in the CLOSE-UP study
CLOSE-UP: Patients
14 days follow-up
(n=483 (96.4 %))
FemoSeal
(n=507)
(n=481 (96.2 %))
Manual compression
Patients randomized in the CLOSE-UP study
(n=1014)
In analysis
(n=501)
(n=500)
Excluded
(n=6)
Intervention = 2
Re-CAG = 1
Withdrawal = 3
(n=7)
Intervention = 4
Withdrawal = 2

13. CLOSE-UP: Baseline dataMC
(n=500)
FemoSeal (n=501) p
Age, yrs
64.3 ± 11
65.2 ± 11
0.19
Male gender (%)
310 (62.0)
311 (62.3)
0.94
Smoker (%)
93 (20.0)
104 (22.1)
0.57
Statin tx (%)
269 (53.8)
315 (63.1)
0.003
Hypertension (%)
255 (51.0)
291 (58.3)
0.02
Diabetes (%)
83 (16.6)
85 (17.0)
0.62
Prior AMI (%)
77 (16.6)
94 (20.0)
0.14
Prior PCI (%)
91 (18.2)
117 (23.5)
0.04
Peripheral artery disease (%)
55 (11.0)
72 (14.4)
0.22
Body mass index, kg/m
26.8±4.6
27.4±5.0
0.047
Creatinine, μmol/L
80 [69-95]
80 [67-95]
0.89

14. CLOSE-UP: Antithrombotic TXMC
(n=500)
FemoSeal (n=501) p
Aspirin (%)
381 (76.2)
402 (80.2)
0.30
Clopidogrel (%)
119 (23.8)
131 (26.2)
0.49
Dipyridamol (%)
9 (1.8)
8 (1.6)
0.95
Prasugrel (%)
1 (0.2)
3 (0.6)
0.60
Fondaparinux (%)
42 (8.4)
40 (8.0)
0.74
Dalteparin/enoxaparin (%)
0.13
Bivalirudin (%)
1.00
Abciximab (%)
Warfarin (%)
55 (11.0)
63 (12.6)
0.64
INR
38 (7.7)
INR 3.1- 1 3
0.87

15. CLOSE-UP: Procedural dataMC
(n=500)
FemoSeal (n=501) p
More than one arterial puncture, n (%)
43 (8.6)
61 (12.2)
0.08
Catheter size 6F
500 (100)
501 (100)
1.00
CAG time excl. closure, min
7.0 [5-10]
0.72
Systolic blood pressure, mmHg
140±23
139±23
0.33
Diastolic blood pressure, mmHg
73±13
73±14
0.97
Local anesthetic (Xylocain )
180 [ ]
0.87

16. CLOSE-UP: Procedural dataMC
(n=500)
FemoSeal (n=501) p
More than one arterial puncture, n (%)
43 (8.6)
61 (12.2)
0.08
Catheter size 6F
500 (100)
501 (100)
1.00
CAG time excl. closure, min
7.0 [5-10]
0.72
Systolic blood pressure, mmHg
140±23
139±23
0.33
Diastolic blood pressure, mmHg
73±13
73±14
0.97
Local anesthetic (Xylocain )
180 [ ]
0.87
Time to haemostasis, min
8.0 [6-10]
1.0 [1-1]
<
Technical / deployment failure, n (%) -
32 (6.4)
0.0001
Time to mobilization, min
84±56
89±38
0.11

17. CLOSE-UP: Primary Endpoint

18. CLOSE-UP: Primary Endpoint%
6.7 %
2.2 %
P=0.002

19. CLOSE-UP: Results 14 days access site MAVE* 1.0% 0.6% 0.70 MC (n=500)
FemoSeal (n=501) p
14 days access site MAVE*
1.0%
0.6%
0.70
Pseudoaneurysm
1 (0.2%)
2 (0.4%)
1.00
Infection
Need for vascular surgery
0 (0)
Major bleeding
0.50
Retroperitoneal bleeding
* Pseudoaneurysm, A-V fistula, surgical repair, major bleeding and infection

20. CLOSE-UP: Results MC (n=500) FemoSeal (n=501) p
14 days haematoma > 5 cm (self assessment)
8.7 %
6.4 %
0.20
Need for new compression (in-hospital)
8.8 %
11.4%
0.18
Medical evaluation after discharge
4.2%
3.8%
0.82

21. CLOSE-UP: Conclusion
Closure of femoral artery access by the FemoSeal VCD after CAG was associated with significantly fewer in-hospital large haematomas compared to manual compression
Closure was faster by FemoSeal
Incidence of major adverse vascular events were low and similar in the two groups
No differences were detected in patient measured large haematomas at 14 days, nor in the need for medical contact after discharge.

22. CLOSE-UP: Conclusion
Closure of femoral artery access by the FemoSeal VCD after CAG was associated with significantly fewer in-hospital large haematomas compared to manual compression
Closure was faster by FemoSeal
Incidence of major adverse vascular events were low and similar in the two groups
No differences were detected in patient measured large haematomas at 14 days, nor in the need for medical contact after discharge.
Acknowledgments to the staff at Dep. of Cardiology
Aarhus University Hospital, Skejby, Denmark