VeClose trial Cyanoacylate closure vs. RF ablation 36-month results LINC 2018, Leipzig 31 st Jan 2018 Tobias 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 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) USA: American Venous Forum 2011 UK: NICE Guidelines 2013
Laser: 12 devices 940nm 532 2100nm 1320nm 1470nm (810nm) Bare fibre Radial Radial 2ring RFA: 3 systems ClosureFast TM RFiTT EVRF FCare
Do we need more methods and devices?
Thermal ablation has side effects Heat Tumescent anesthesia
Thermal ablation has side effects Heat Tumescent anesthesia Needle
Thermal ablation has side effects Heat Tumescent anesthesia Pain Hyperpigmentation Risk of nerve damage Needle
Non-thermal ablation using adhesive closure
Adhesive closure History 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
Adhesive closure History Methyl 2-cyanoacrylate 1960s nerve lesions Isobutyl 2-cyanoacrylate 1970s wound closure N-octyl-cyanoacrylate 1996 wound closure N-butyl 2-cyanoacrylate 2011 Venaseal TM
Adhesive closure Occlusion rate 90,3-100,0% Hirsch T, Phlebologie 2017(46)143-7
VeClose Study Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
VeClose Study Overview Title Purpose VenaSeal Closure System vs. Radiofrequency Ablation for Incompetent Great Saphenous Veins Demonstrate the safety and effectiveness of the VenaSeal Closure System for the treatment of lower extremity truncal reflux compared to RFA (ClosureFAST TM system) Study Design Enrollment Sites Follow-up US multi-center, randomized controlled IDE study. The study takes a noninferiority approach to effectiveness for anatomical closure at 3 months. Effectiveness at 36 months is assessed and compared across groups. 242 (20 roll-in and 222 randomized) subjects enrolled at 10 study sites (Sept 2013) Follow-up visits at 3 days post-procedure, 1, 3, 6, 12, 24, 36 and 60 months. Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
VeClose Study Sites and Enrollments Intraoperative Pain evaluation : Site # Site Name Following procedure, self PI rated pain experienced Location during 2 phases of the treatment procedure on a 0-10 NRS 11 Morrison Vein Institute Phase 1: From initial Morrison local anesthesiascottsdale, injection AZ at the access 2 site to 14 Primary Endpoint Secondary Endpoints Complete closure of the target vein at 3 months after index Roll-in procedure as judged by the core laboratory. Complete closure is defined as Doppler ultrasound examination showing closure along venous entire access treated with the target micro-access vein segment catheter with no discrete segments of patency exceeding 5 cm. 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 - none 1 - involving <25% of the treatment area 2-25%-50% 3-50%-75% 4-75%-100% McEnroe Virginia Beach, VA 2 24 5 - extension above or below the treatment segment Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94 Randomized 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 22 Venous Institute of Buffalo Vasquez Amherst, NY 2 9 20 222 242
VeClose Study Endpoints 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. Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
VeClose Study Endpoints Primary Endpoint Secondary Endpoints 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 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 venous entire access treated with the target micro-access vein segment catheter with no discrete segments of patency exceeding 5 cm. 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 - none 1 - involving <25% of the treatment area 2-25%-50% 3-50%-75% 4-75%-100% 5 - extension above or below the treatment segment Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
VeClose Study Endpoints 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-Pathophysiology classification; GSV, great saphenous vein; EQ-5D, EuroQoL 5 Dimension; QoL, Quality of Life; TTO, time trade-off; VCSS, vein clinical severity score. Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
VeClose Study Design Enrolled (N=242) Randomized (1:1) and treated Subjects (N=222) CAC Roll-In group Subjects (N=20) CAC (n=108) RFA (n=114) Evaluation of perioperative parameters Baseline assessments Intraoperative pain Ecchymosis Follow up at day 3; and at 1,3,6, 12, 24, 36, 60 months Reevaluation of clinical assessments and adverse events Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
VeClose Study Demographic and Baseline Characteristics 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 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 Mean trade-off; EQ-5D VCSS, TTOvein clinical severity score. 0.935 ± 0.113 0.918± 0.116 0.29 Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
VeClose Study Pain Scores Tumescent anesthesia volume (ml) CAC (N=108) Not applicable RFA (N=114) 272 - Lidocaine use (ml) 1.6 2.7 0.1 Cyanoacrylate delivered (ml) 1.2 N/A - Intraoperative pain P-value During vein access 1.6 2.0 0.13 During treatment 2.2 2.4 0.11 Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
VeClose Study Ecchymosis at Day 3 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). Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
VeClose Study Primary Endpoint Complete Closure 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) Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
VeClose Study Primary endpoint Complete Closure 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) Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
VeClose Study Primary endpoint Complete Closure Month 36 94.4% (72) 91.9% (74) Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
VCSS, Mean (SE) VeClose Study VCSS: disease severity over time 8 6 4 2 108 108105104 101 9 87 72 114 114110108 105 5 84 74 0 1 3 6 9 12 7 Follow-up Months 24 36 RFA 1.69 ± 2.42 VS 1.25 ± 1.60 p=0.5643 Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
AWQ, Mean (SE) VeClose Study AVVQ: pain, edema, skin changes, compression use 2 5 2 0 1 5 1 0 5 RFA 8.21 ± 7.76 VS 7.33 ± 6.19 p=0.6778 0 107 102 104 111 109 108 100 105 95 95 0 1 3 6 12 24 36 Follow-up Months 86 84 71 73 Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
EQ-5D Health Thermometer, Mean (SE) VeClose Study EQ-5D: mobility, self-care, usual activities, pain, anxiety 100 VS 89.69 ± 12.00 RFA 88.09 ± 11.66 p=0.8024 80 70 108 105 114 110 104 108 99 105 95 97 0 1 3 6 12 24 36 Follow-up Months Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94 87 84 72 74
VeClose Study Adverse Events 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 thrombus No allergic events reported No unanticipated adverse events Most events occurred in the first 30 days, were mild and self-limiting Delayed adverse events were minimal to non-existent Morrison N, Gibson K, McEnroe S et al., J Vasc Surg 2015. 61.985-94
Roll-in Phase Analysis of clinical study of CAC for incompetent GSV Objectives: Efficacy and safety outcomes of the VeClose roll-in (training) group vs. randomized CAC/RFA Results: Mean procedure 3min longer 3-month closure rate 100% Procedural pain, post-procedural QoL, AE similar 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. Kolluri R, et al. J Vasc Surg and Lym Dis 2016;4;407-15
VeClose Study Summary at 36 Months 1. VenaSeal procedure resulted in a reported closure rate of 94.4%, demonstrating continued, noninferiority 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
Thank you for your attention! Tobias Hirsch Vein Competency Centre Halle www.gefaessmedizin-hirsch.de
See you at the social dinner! Tobias Hirsch and his marvellous Valentine B Live at Moritzbastei Feb 1 st 2018