VeClose trialCyanoacylate closure vs. RF ablation 36-month results

LINC 2018, Leipzig 31st Jan 2018Tobias Hirsch, Halle, Germany

www.gefaessmedizin-hirsch.de

Disclosure

Tobias Hirsch

I have the following potential conflicts of interest to report:

Consulting (Medtronic, Sigvaris, L+R, Medi, Bauerfeind)

Employment in industry

Stockholder of a healthcare company

Owner of a healthcare company

Other(s)

I do not have any potential conflict of interest

Thermal ablation

USA: American Venous Forum 2011 UK: NICE Guidelines 2013

is standard

USA: American Venous Forum 2011 UK: NICE Guidelines 2013

High occlusion rate!Laser: 93.0% (3yr)

RFA: 93.2%

Stripping: 93.5%

Rasmussen et al., JVascSurg 2013

USA: American Venous Forum 2011 UK: NICE Guidelines 2013

High occlusion rate!Laser: 84.8% (5yr)

RFA: 88.7%

Stripping: 93.5%

Balint et al., Vascular 2016 (862 articles, 17 RCT)

Laser: 12 devices940nm532 – 2100nm1320nm1470nm(810nm)Bare fibreRadialRadial 2ring

RFA: 3 systemsClosureFastTM

RFiTT®EVRF® FCare

Do we need more methodsand devices?

Thermal ablation has side effects

Heat Tumescent anesthesia

Thermal ablation has side effects

NeedleHeat Tumescent anesthesia

Thermal ablation has side effects

NeedleHeat Tumescent anesthesia

Pain

Hyperpigmentation

Risk of nerve damage

Non-thermal ablation using adhesive closure

Methyl 2-cyanoacrylate 1960s nerve lesions

Isobutyl 2-cyanoacrylate 1970s wound closure

N-octyl-cyanoacrylate 1996 wound closure

N-butyl 2-cyanoacrylate 1989 intravascular use

History

Adhesive closure

Methyl 2-cyanoacrylate 1960s nerve lesions

Isobutyl 2-cyanoacrylate 1970s wound closure

N-octyl-cyanoacrylate 1996 wound closure

N-butyl 2-cyanoacrylate 2011 VenasealTM

History

Adhesive closure

Occlusion rate

Adhesive closure

Hirsch T, Phlebologie 2017(46)143-7

90,3-100,0%

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

Overview

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

TitleVenaSeal Closure System vs. Radiofrequency Ablation for Incompetent Great Saphenous Veins

PurposeDemonstrate the safety and effectiveness of the VenaSeal Closure System for the treatment of lower extremity truncal reflux compared to RFA (ClosureFASTTM system)

Study Design

US multi-center, randomized controlled IDE study. The study takes a non-inferiority approach to effectiveness for anatomical closure at 3 months. Effectiveness at 36 months is assessed and compared across groups.

Enrollment Sites

242 (20 roll-in and 222 randomized) subjects enrolled at 10 study sites (Sept 2013)

Follow-upFollow-up visits at 3 days post-procedure, 1, 3, 6, 12, 24, 36 and 60 months.

Sites and Enrollments

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

Primary Endpoint

Complete closure of the target vein at 3 months after index procedure as judged by the core laboratory. Complete closure is defined as Doppler ultrasound examination showing closure along entire treated target vein segment with no discrete segments of patency exceeding 5 cm.

SecondaryEndpoints

Intraoperative Pain evaluation :Following procedure, self rated pain experienced during 2 phases of the treatment procedure on a 0-10 NRS• Phase 1: From initial local anesthesia injection at the access site to

venous access with the micro-access catheter• Phase 2: From introduction of the RFA or CAC catheter to completion

of vein treatment and device removal

Ecchymosis at Day 3:Investigator assessment of ecchymosis along the treated area using a 0-5 point grading scale 0 - none1 - involving <25% of the treatment area2 - 25%-50%3 - 50%-75%4 - 75%-100%5 - extension above or below the treatment segment

Site # Site Name PI LocationRoll-in Randomized

11 Morrison Vein Institute Morrison Scottsdale, AZ 2 14

12 Vein Clinics of America King, Hlavcek Oakbrook Terrace, IL 2 19

13 Inovia Vein Specialty Center Jones Bend, OR 2 44

14 Lake Washington Vascular Gibson Bellevue, WA 2 58

16 Radiology Imaging Associates Spencer Greenwood Village, CO 2 4

17 GBK Cosmetic Laser Dermatology Goldman San Diego, CA 2 24

18 Prairie Education & Research Cooperative Kolluri, Matos Springfield, IL 2 9

19 Maryland Laser Skin & Vein Institute Weiss Hunt Valley, MD 2 17

20 Vein Center of Virginia/Sentara Vascular Specialists

McEnroe Virginia Beach, VA 2 24

22 Venous Institute of Buffalo Vasquez Amherst, NY 2 9

20 222

242

Endpoints

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

Primary Endpoint

Complete closure of the target vein at 3 months after index procedure as judged by the core laboratory. Complete closure is defined as a Doppler ultrasound examination showing closure along entire treated target vein segment with no discrete segments of patency exceeding 5 cm.

Endpoints

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

Primary Endpoint

Complete closure of the target vein at 3 months after index procedure as judged by the core laboratory. Complete closure is defined as Doppler ultrasound examination showing closure along entire treated target vein segment with no discrete segments of patency exceeding 5 cm.

SecondaryEndpoints

Intraoperative pain evaluation:Following procedure, self rated pain experienced during 2 phases of the treatment procedure on a 0-10 NRS• Phase 1: From initial local anesthesia injection at the access site to

venous access with the micro-access catheter• Phase 2: From introduction of the RFA or CAC catheter to completion

of vein treatment and device removal

Ecchymosis at day 3:Investigator assessment of ecchymosis along the treated area using a point scale of 0-5

0 - none1 - involving <25% of the treatment area2 - 25%-50%3 - 50%-75%4 - 75%-100%5 - extension above or below the treatment segment

Endpoints

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

Additional endpoints

Assessments related to venous disease severity:

Change in VCSS scores

Change in CEAP scores

Assessments related to QoL:

Change in AVVQ scores

Change in EQ-5D TTO scores

Comparison of adverse event rates related to target GSV

AVVQ, Aberdeen Varicose Vein Questionnaire; CEAP, Clinical-Etiology-Anatomy-Pathophysiologyclassification; GSV, great saphenous vein; EQ-5D, EuroQoL 5 Dimension; QoL, Quality of Life; TTO, time trade-off; VCSS, vein clinical severity score.

Design

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

Enrolled (N=242)

RFA (n=114)CAC (n=108)

Randomized (1:1) and treatedSubjects (N=222)

Follow up at day 3; and at 1,3,6, 12, 24, 36, 60 months

CAC Roll-In groupSubjects (N=20)

Baseline assessments

Intraoperative pain

Reevaluation of clinical assessments and adverse events

Evaluation of perioperative parameters

Ecchymosis

Demographic and Baseline Characteristics

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

AVVQ, aberdeen varicose vein questionnaire; CEAP, clinical-etiology-anatomy-pathophysiology classification; GSV, great saphenous vein; EQ-5D, euro quality of life-5D; QoL, quality of life; TTO, time trade-off; VCSS, vein clinical severity score.

Baseline Characteristics CAC (N=108)

RFA (N=114)

P-value

Age (years) 49.0 50.5 0.34

Body Mass Index 27.0 27.0 0.95

Mean GSV diameter (mm)

Proximal 6.3 6.6 0.15

Mid-thigh 4.9 5.1 0.28

Mean treatment length (cm) 32.8 (108) 35.1 (114) 0.17

Mean VCSS 5.5 ± 2.6 5.6 ± 2.6 0.99

Mean AVVQ 18.9 ± 9.0 19.4 ± 9.9 0.72

Mean EQ-5D TTO 0.935 ± 0.113 0.918± 0.116 0.29

Pain Scores

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

CAC (N=108)

RFA (N=114)

P-value

Tumescent anesthesia volume (mL)

Not applicable

272 -

Lidocaine use (mL) 1.6 2.7 0.1

Cyanoacrylate delivered (mL) 1.2 N/A -

Intraoperative pain

During vein access 1.6 2.0 0.13

During treatment 2.2 2.4 0.11

Ecchymosis at Day 3

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

Assessed by investigators with a 5-point scale on day 3

Subjects treated with VenaSeal™

system had significantly less ecchymosis on day 3 compared to RFA (p< 0.01).

Primary Endpoint – Complete Closure

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

Time Point VenaSeal RFA

Day 3 100% (108) 99.1% (114)

Month 1 100% (105) 87.3% (110)

Month 3* 99% (104) 95.4% (108)

Month 6 99% (101) 96.2% (105)

Month 12 96.8% (95) 95.9% (97)

Month 24 95.3% (86) 94% (84)

Month 36 94.4% (72) 91.9% (74)

Primary endpoint – Complete Closure

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

Time Point VenaSeal RFA

Day 3 100% (108) 99.1% (114)

Month 1 100% (105) 87.3% (110)

Month 3* 99% (104) 95.4% (108)

Month 6 99% (101) 96.2% (105)

Month 12 96.8% (95) 95.9% (97)

Month 24 95.3% (86) 94% (84)

Month 36 94.4% (72) 91.9% (74)

Primary endpoint – Complete Closure

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

Month 36 94.4% (72) 91.9% (74)

VCSS: disease severity over time

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

0 1 3 6 12 24 36

2

4

6

8

Follow-up Months

VC

SS

, M

ea

n (

SE

)

108

114

105

110

104

108

9

5

9

7

87

84

72

74

101

105

108

114

RFA 1.69 ± 2.42

VS 1.25 ± 1.60

p=0.5643

AVVQ: pain, edema, skin changes, compression use

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

RFA 8.21 ± 7.76

VS 7.33 ± 6.19

p=0.6778

0

5

1

0

1

5

2

0

2

5

0 1 3 6 12 24 36

107

111

102

109

104

108

100

105

95

95

86

84

71

73

Follow-up Months

AW

Q,

Me

an

(S

E)

EQ-5D: mobility, self-care, usual activities, pain, anxiety

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

VS 89.69 ± 12.00

RFA 88.09 ± 11.66

p=0.8024

0 1 3 6 12 24 36

70

80

100

Follow-up Months

EQ

-5D

Hea

lth

Th

erm

om

ete

r, M

ea

n (

SE

)

108

114

105

110

104

108

99

105

95

97

87

84

72

74

Adverse Events

VeClose Study

Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94

24-36 Month AE Device or Procedure Reporting

Adverse Events Reported Device/ Procedure Related

CAC 2 (phlebitis, scar at access site)

RFA 0

VenaSeal AEs from 0 to 36 months:No reports of deep vein thrombusNo allergic events reportedNo unanticipated adverse eventsMost events occurred in the first 30 days, were mild and self-limitingDelayed adverse events were minimal to non-existent

Objectives: Efficacy and safety outcomes of the VeCloseroll-in (training) group vs. randomized CAC/RFA

Results: Mean procedure 3min longer

3-month closure rate – 100%

Procedural pain, post-procedural QoL, AE similar

of clinical study of CAC for incompetent GSV

Roll-in Phase Analysis

Kolluri R, et al. J Vasc Surg and Lym Dis 2016;4;407-15

“Despite the physician’s lack of prior experience, initial treatment with CAC leads to comparable efficacy and safety results to RFA and is associated with a relatively short learning period.”

1. VenaSeal™ procedure resulted in a reported closure rate of 94.4%, demonstrating continued, non-inferiority compared to RFA (P=0.005)

2. VCSS, AVVQ and EQ-5D outcomes demonstrated statistically significant improvement from baseline with sustained results over time; no difference between treatment groups

3. No reported DVTs, allergic reactions, or other SAEs. Early events were mild and self-limiting; delayed events were uncommon

4. VenaSeal™ is easy to learn

Summary at 36 Months

VeClose Study

Thank you for your attention!

Tobias HirschVein Competency Centre Hallewww.gefaessmedizin-hirsch.de

See you at the social dinner!

Tobias Hirschand his marvellous ”Valentine B”Live at Moritzbastei Feb 1st 2018