Randomized controlled multicenter trial of N-butyl cyanoacrylate endovenous ablation and radiofrequency endovenous ablation for incompetent great saphenous veins

doi:10.16139/j.1007-9610.2025.04.03

Abstract

Abstract:

Objective To compare the 12-month efficacy and safety of N-butyl cyanoacrylate (NBCA) versus radiofrequency ablation (RFA) in treating great saphenous vein (GSV) insufficiency. Methods A total of 155 patients with GSV insufficiency from five centers were randomly allocated to the NBCA group or RFA group. Postoperative efficacy and safety outcomes were evaluated. Results Immediate postoperative closure rates of the GSV trunk were 100% in both groups. The closure rates of NBCA and RFA group were 98.6% and 98.5% at 3 months, 97.1% and 98.5% at 6 months, 98.1% and 95.9% at 12 months, with no statistically significant differences (P>0.05). After treatment, CEAP classification improved significantly from baseline in both groups. In terms of safety, 1 case of phlebitis, 1 case of ablation-related thrombus extension (ARTE) and 2 cases of calf muscle venous thrombosis(CMVT) occurred in the NBCA group, while 2 cases of limb numbness, 1 case of persistent thigh pain and 2 cases of CMVT in the RFA group. All reported serious adverse events in both groups were assessed as unrelated to the medical device or the trial procedure. Conclusions NBCA demonstrates non-inferior efficacy and safety compared to RFA for treating GSV insufficiency over 12 months.

Key words: Great saphenous vein(GSV) insufficiency, N-butyl cyanoacrylate(NBCA), Endovenous nonthermal ablation, Radiofrequency ablation (RFA)

CLC Number:

R654.4

JIANG Jinsong, WU Hao, WANG Xinye, XIE Dang, WANG Changming, FANG Xin, HE Chunshui, LIU Zhenjie. Randomized controlled multicenter trial of N-butyl cyanoacrylate endovenous ablation and radiofrequency endovenous ablation for incompetent great saphenous veins[J]. Journal of Surgery Concepts & Practice, 2025, 30(04): 302-309.

Figures/Tables 7

Fig 1

Tab 1

Tab 2

Tab 3

Fig 2

Tab 4

Tab 5

References 32

[1]	ROBERTSON L, EVANS C, FOWKES F G. Epidemio-logy of chronic venous disease[J]. Phlebology, 2008, 23(3):103-111.
[2]	RABE E, GUEX J J, PUSKAS A, et al. Epidemiology of chronic venous disorders in geographically diverse populations: results from the vein consult program[J]. Int Angiol, 2012, 31(2):105-115.
[3]	WINTERBORN R J, FOY C, EARNSHAW J J. Causes of varicose vein recurrence: late results of a randomized controlled trial of stripping the long saphenous vein[J]. J Vasc Surg, 2004, 40(4):634-639. pmid: 15472588
[4]	MORRISON N, GIBSON K, VASQUEZ M, et al. VeClose trial 12-month outcomes of cyanoacrylate closure versus radiofrequency ablation for incompetent great saphenous veins[J]. J Vasc Surg Venous Lymphat Disord, 2017, 5(3):321-330.
[5]	ALHEWY M A, ABDO E M, GHAZALA E A E, et al. Outcomes of cyanoacrylate closure versus radiofrequency ablation for the treatment of incompetent great saphenous veins[J]. Ann Vasc Surg, 2024,98:309-316.
[6]	吴昊, 卢凯平, 孙婧, 等. 氰基丙烯酸酯胶腔内常温闭合与射频腔内热闭合治疗大隐静脉功能不全的随机对照研究[J]. 中华普通外科杂志, 2023, 38(8):605-610.
	WU H, LU K P, SUN J, et al. Randomized controlled trial of endovenous N-butylcyanoacrylate endovenous nonthermal ablation and radiofrequency endovenous thermal ablation for incompetent great saphenous veins[J]. Chin J Gen Surg, 2023, 38(8):605-610.
[7]	LURIE F, PASSMAN M, MEISNER M, et al. The 2020 update of the CEAP classification system and reporting standards[J]. J Vasc Surg Venous Lymphat Disord, 2020, 8(3):342-352. doi: S2213-333X(20)30063-9 pmid: 32113854
[8]	VAN DEN BOS R, ARENDS L, KOCKAERT M, et al. Endovenous therapies of lower extremity varicosities: a meta-analysis[J]. J Vasc Surg, 2009, 49(1):230-239. doi: 10.1016/j.jvs.2008.06.030 pmid: 18692348
[9]	NESBITT C, BEDENIS R, BHATTACHARYA V, et al. Endovenous ablation (radiofrequency and laser) and foam sclerotherapy versus open surgery for great saphenous vein varices[J]. Cochrane Database Syst Rev, 2014,(7):CD005624.
[10]	CARROLL C, HUMMEL S, LEAVISS J, et al. Systematic review, network meta-analysis and exploratory cost-effectiveness model of randomized trials of minimally invasive techniques versus surgery for varicose veins[J]. Br J Surg, 2014, 101(9):1040-1052.
[11]	ALMEIDA J I, JAVIER J J, MACKAY E G, et al. Two-year follow-up of first human use of cyanoacrylate adhesive for treatment of saphenous vein incompetence[J]. Phlebology, 2015, 30(6):397-404. doi: 10.1177/0268355514532455 pmid: 24789750
[12]	MORRISON N, GIBSON K, MCENROE S, et al. Randomized trial comparing cyanoacrylate embolisation and radiofrequency ablation for incompetent great saphenous veins (VeClose)[J]. J Vasc Surg, 2015, 61(4):985-994.
[13]	RASMUSSEN L, LAWAETZ M, BJOERN L, et al. Randomized clinical trial comparing endovenous laser ablation and stripping of the great saphenous vein with clinical and duplex outcome after 5 years[J]. J Vasc Surg, 2013, 58(2):421-426. doi: 10.1016/j.jvs.2012.12.048 pmid: 23768792
[14]	ALMEIDA J I, MIN R J, RAABE R, et al. Cyanoacrylate adhesive for the closure of truncal veins: 60-day swine model results[J]. Vasc Endovascular Surg, 2011, 45(7):631-635.
[15]	GIBSON K, MORRISON N, KOLLURI R, et al. Twenty-four month results from a randomized trial of cyanoacrylate closure versus radiofrequency ablation for the treatment of incompetent great saphenous veins[J]. J Vasc Surg Venous Lymphat Disord, 2018, 6(5):606-613.
[16]	WITTENS C, DAVIES A H, BÆKGAARD N, et al. Editor's choice - management of chronic venous disease: clinical practice guidelines of the European Society for Vascular Surgery (ESVS)[J]. Eur J Vasc Endovasc Surg, 2015, 49(6):678-737.
[17]	GLOVICZKI P, COMEROTA A J, DALSING M C, et al. The care of patients with varicose veins and associated chronic venous diseases: clinical practice guidelines of the society for vascular surgery and the American Venous Forum[J]. J Vasc Surg, 2011, 53(5 Suppl):2S-48S.
[18]	CHI Y W, WOODS T C. Clinical risk factors to predict deep venous thrombosis post-endovenous laser ablation of saphenous veins[J]. Phlebology, 2014, 29(3):150-153. doi: 10.1177/0268355512474254 pmid: 23434616
[19]	ROSALES-VELDERRAIN A, GLOVICZKI P, SAID S M, et al. Pulmonary embolism after endovenous thermal ablation of the saphenous vein[J]. Semin Vasc Surg, 2013, 26(1):14-22.
[20]	SUFIAN S, ARNEZ A, LAKHANPAL S. Case of the disappearing heat-induced thrombus causing pulmonary embolism during ultrasound evaluation[J]. J Vasc Surg, 2012, 55(2):529-531. doi: 10.1016/j.jvs.2011.07.070 pmid: 21958568
[21]	KIGUCHI M M, REYNOLDS K B, CUTLER B, et al. The need for perforator treatment after VenaSeal and ClosureFast endovenous saphenous vein closure in CEAP 6 patients[J]. J Vasc Surg Venous Lymphat Disord, 2021, 9(6):1510-1516.
[22]	BISSACCO D, STEGHER S, CALLIARI F M, et al. Saphenous vein ablation with a new cyanoacrylate glue device: a systematic review on 1000 cases[J]. Minim Invasive Ther Allied Technol, 2019, 28(1):6-14. doi: 10.1080/13645706.2018.1464029 pmid: 29671660
[23]	ALMEIDA J I, JAVIER J J, MACKAY E G, et al. Thirty-sixth-month follow-up of first-in-human use of cyanoacrylate adhesive for treatment of saphenous vein incompetence[J]. J Vasc Surg Venous Lymphat Disord, 2017, 5(5):658-666. doi: S2213-333X(17)30166-X pmid: 28818217
[24]	PROEBSTLE T M, ALM J, DIMITRI S, et al. The European multicenter cohort study on cyanoacrylate embolization of refluxing great saphenous veins[J]. J Vasc Surg Venous Lymphat Disord, 2015, 3(1):2-7. doi: 10.1016/j.jvsv.2014.09.001 pmid: 26993674
[25]	KORAMAZ İ, EL KILIÇ H, GÖKALP F, et al. Ablation of the great saphenous vein with nontumescent n-butyl cyanoacrylate versus endovenous laser therapy[J]. J Vasc Surg Venous Lymphat Disord, 2017, 5(2):210-215.
[26]	AU -YEUNG C L K, TSE O H R, PANG Y C S, et al. Review of thermal and non-thermal based endovenous treatment: our local experience[J]. Surg Pract, 2020, 24(4):151-155.
[27]	TANG T Y, YAP C J Q, CHAN S L, et al. Early results of an Asian prospective multicenter VenaSeal real-world postmarket evaluation to investigate the efficacy and safety of cyanoacrylate endovenous ablation for varicose veins[J]. J Vasc Surg Venous Lymphat Disord, 2021, 9(2):335-345.e2. doi: 10.1016/j.jvsv.2020.03.020 pmid: 32387378
[28]	ZIERAU U T. 100 months experiences with VenaSeal^® vein glue: long time follow-up study conducted on 2912 truncal saphenous veins in 1509 cases[J]. J Angiol Vasc Surg, 2020,5:54.
[29]	EROGLU E, YASIM A. A randomised clinical trial comparing N-butyl cyanoacrylate, radiofrequency ablation and endovenous laser ablation for the treatment of superficial venous incompetence: two year follow up results[J]. Eur J Vasc Endovasc Surg, 2018, 56(4):553-560.
[30]	ALMEIDA J I, JAVIER J J, MACKAY E, et al. First human use of cyanoacrylate adhesive for treatment of saphenous vein incompetence[J]. J Vasc Surg Venous Lymphat Disord, 2013, 1(2):174-180. doi: 10.1016/j.jvsv.2012.09.010 pmid: 26992340
[31]	GIBSON K, FERRIS B. Cyanoacrylate closure of incompetent great, small and accessory saphenous veins without the use of post-procedure compression: initial outcomes of a post-market evaluation of the VenaSeal System (the WAVES study)[J]. Vascular, 2017, 25(2):149-156. doi: 10.1177/1708538116651014 pmid: 27206470
[32]	YIĞIT G. How effective is cyanoacrylate closure in small saphenous vein insufficiency? A single center experience[J]. Vascular, 2022, 30(6):1182-1188.

Clinical data	NBCA group （n=78）	RFA group （n=77）	Statistical value	P value
Gender			χ²=0.50	0.48
Male	30（38.5）	34（44.2）
Female	48（61.5）	43（55.8）
Age(years)	58.1±11.6	58.0±11.2	t=0.08	0.94
CEAP classification				<0.001
C2	23（29.5）	18（23.4）
C3	6（7.7）	21（27.3）
C4a	35（44.9）	36（46.8）
C4b	5（6.4）	1（1.3）
C5	9（11.5）	1（1.3）
VCSS	4.1±2.6	3.7±1.9	U=2650.5	0.21
AVVQ	5.0±4.0	4.2±3.4	U=2699.0	0.27
GSV diameter（mm）	8.0±2.3	7.6±2.1	t=1.34	0.18
Reflux time（s）	5.3±3.6	5.1±2.4	t=1.61	0.11

Closure rates	NBCA group	RFA group	P value
at 3 months	98.6%(70/71)	98.5%(67/68)	1.00
at 6 months	97.1%(66/68)	98.5%(64/65)	0.62
at 12 months	98.1%(52/53)	95.9%(47/49)	0.61

Item	NBCA group	RFA group	χ² value	P value
CEAP grade at 3 months			1.67	0.43
C0-C1	53（74.6）	54（79.4）
C2-C3	8（11.3）	9（13.2）
C4a	10（14.1）	5（7.4）
CEAP grade at 6 months			0.60	0.74
C0-C1	60（87.0）	60（90.9）
C2-C3	2（2.9）	1（1.5）
C4a	7（10.1）	5（7.6）

Item	NBCA group	RFA group	P value
Thrombus	3.8(3/78)	2.6(2/77)	1.00
Petechia	1.3(1/78)	5.2(4/77)	0.21
Pain	2.6(2/78)	2.6(2/77)	1.00
Numbness	0	2.6(2/77)	0.24
Infection	3.8(3/78)	2.6(2/77)	1.00
Pigment	2.6(2/78)	0	0.24