Efficacy and safety of mechanochemical ablation versus laser ablation in the treatment of primary great saphenous vein reflux: A randomized,open,parallel controlled clinical trial

Abstract

Objective

To evaluate the efficacy of a new mechanochemical ablation (MOCA) device versus endovenous laser ablation (EVLA) for primary great saphenous vein (GSV) reflux.

Materials and methods

Prospectively analyze the demographics, treatment detail and outcomes data of 57 primary GSV reflux patients. Patients were randomly assigned to MOCA or EVLA group with random envelope method. Primary endpoint was 6-month closure rate of GSV. Secondary endpoint including technical success rate, the venous clinical severity score (VCSS), chronic venous insufficiency questionnaire (CIVIQ-20) score and visual analogue scale (VAS) for pain.

Results

The procedures were well tolerated according to the VAS score. The 6-month closure rate was 85.71% in MOCA and 96.55% in EVLA group (p = .194). Significant changes were observed in regard of VCSS and CIVIQ-20 score at 6-month follow-up. Skin paresthesia occurred in 0 in MOCA and 5 in EVLA group.

Conclusion

The new MOCA device is safe and effective in treating primary great saphenous vein reflux. The 6-month closure rate is non-inferior compared with EVLA. However, the long-term results need further follow-up.

Keywords

Primary great saphenous vein reflux mechanochemical ablation endovenous laser ablation

Introduction

Varicose vein is a common problem worldwide, affecting approximately 25% of the population^1,2 and causing significant impairment in health related quality of life (HRQoL).^3–5 Symptoms span from cosmetic worries to severe refractory ulcer can present in patients with primary great saphenous vein (GSV) reflux.⁶

The current treatment options for primary GSV reflux are multiple. Conventional surgery, consisting of ligation and stripping, had been the “golden standard” for a long time. However, it may be associated with significant postoperative morbidity.⁷ In the past decades, endovenous thermal ablation (laser and radiofrequency) have become widely used as alternatives to open surgery because of minimally invasive nature, fewer complications and shorter recovery period.⁸ Tumescent local anesthesia fluid injection is necessary during endovenous thermal ablation to reduce heat-induced complications. In an attempt to avoid these complications and unnecessary puncture, non-thermal non-tumescent ablation including foam sclerotherapy, mechanochemical ablation (MOCA) and cyanoacrylate glue embolization have been introduced.⁹ The emergence of non-thermal non-tumescent ablation has added to the controversy over optimal treatment for primary GSV reflux.

MOCA has been widely used in some countries. However, no available commercial device could be used in China so far. The current study aims to assess the efficacy of a new Chinese domestic MOCA device versus endovenous laser ablation (EVLA) in the treatment of primary GSV reflux.

Materials and methods

Study design

This is a randomized, open, parallel controlled non-inferiority clinical trial. Consecutive patients were randomly assigned in a 1:1 ratio to the experimental or control group with random envelope method. Patients in experimental group were treated with a new Chinese domestic MOCA microcatheter (BHKY medical, Beijing, China) and patients in control group were treated with 1470 nm ring laser (LASEmaR 1500™, Eufoton, Italy). We aim to evaluate the efficacy and safety of MOCA microcatheter in the treatment of primary GSV reflux. All data was collected prospectively. The study was approved by the institutional ethics committee of our hospital and written informed consent was obtained from all patients.

The new Chinese domestic MOCA device is called intravenous closure microcatheter, which is produced by BHKY in China. This device is similar to Clarivein by Merit Medical. Four rotational speed was set for the tip: 2000 rpm, 2500 rpm, 3000 rpm and 3500 rpm. The microcatheter length is 45 cm and 65 cm.

Inclusion and exclusion criteria

Inclusion criteria was (1) Age between 18 and 75 years old (including 18 and 75 years old), regardless of gender; (2) The diagnosis was primary GSV reflux (CEAP category, C2-C6), Doppler ultrasound showed GSV valve reflux time > 1.0 s, and the diameter of GSV ≤ 8 mm and ≥ 2 mm; (3) Single leg involved; (4) Sign the ‘informed consent form’ voluntarily.

Exclusion criteria were (1) Allergic to any instrument component or polidocanol, allergic constitution (allergic to 2 or more kinds of food, drug, or pollen); (2) Allergic to alcohol; (3) Inflammation or infection exist at the puncture site; (4) History of varicose vein surgery; (5) Long-term confined to bed rest; (6) Severe tortuosity of GSV, phlebitis, severe peripheral arterial occlusive disease; (7) Acute deep or superficial venous thrombosis and/or pulmonary embolism or high risk of thrombosis, such as history of thromboembolism event and tendency to severe thrombosis; (8) Heart disease with right to left shunt; (9) Pregnant, lactating or planned pregnancy within 6 months; (10) NYHA (New York Heart Association) heart function grade 3-4, liver and kidney dysfunction (Creatinine, Alanine aminotransferase or Aspartate aminotransferase > 2 times of the upper limit of normal range); (11) Bleeding tendency or coagulation disorders (prothrombin time, activated partial thromboplastin time > 1.5 times of the upper limit of normal range); (12) Those who have participated in clinical trials of other medical devices or drugs within 6 months before screening; (13) Mental illness or disorder; (14) Other situations that are not suitable.

Preoperative ultrasound examination

Preoperative ultrasound examination was carried out in standing position to confirm the access site, GSV ablation length and varicosities need ambulatory phlebectomy. If the reflux ended above the knee, we usually choose where the reflux ended as access site. If the reflux ended below the knee, we usually choose 2 cm below the knee as access site in fear of saphenous nerve injury.

Mechanochemical ablation and endovenous laser ablation procedure

The whole procedure was carried out under local anesthesia. Patients were in supine position with slight hip abduction and knee flexion. We punctured GSV under the guidance of ultrasound with a 21-Gauge micro puncture needle (Micropuncture Check-Flo Performer Introducer Set, Cook) and introduced a sheath. The laser or MOCA catheter was inserted until the tip reached about 2 cm below the saphenofemoral junction (SFJ). In EVLA group, perivenous tumescent local anesthesia fluid injection was carried out under ultrasound guidance (10 mL/cm). EVLA was delivered via a ring fiber with 360°emission using a 1470 nm laser generator. Energy density was 40 J/cm with 8W continuous energy delivery.

In MOCA group, the tip rotating speed was 3500 rpm with a recession velocity of 1–2 mm/s. 3% polidocanol was injected simultaneously with the wire rotating. Ultrasound assessment was routinely carried out to ensure safety and evaluate immediate technical success.

After GSV ablation, ambulatory phlebectomy or 1% polidocanol foam injection for varicosities was carried out according to the preoperative plan. After surgery, a constrictive bandage was applied from ankle to groin for 24 h followed by a 23–32 mmHg graduated compression stocking for 14 days.

Technical success refers to instrument arrived at the designated position as expected, completed the operation without device malfunction.

Endpoints

The primary endpoint was 6-month closure rate of GSV. GSV closure was defined as total occlusion (incompressible under ultrasound) and segmental occlusion with reflux time less than 0.5 s.

The secondary endpoint including technical success rate, the venous clinical severity score (VCSS), chronic venous insufficiency questionnaire (CIVIQ-20) score and visual analogue scale (VAS) for pain. The VAS was measured 1-day after surgery. VCSS score and CIVIQ-20 score were measured 6-month atter surgery.

Safety evaluation

Index to evaluate the safety including vital signs monitoring and laboratory test (blood routine, urine routine, blood biochemistry text).

Record any adverse events occurred during the trial. The type of adverse events, occurring time, duration, severity and relationship with the device were recorded.

Device defect refers to malfunction during the normal use of the device, which may endanger health and life safety, including label error, quality problem, and breakdown, et al.

Statistical analysis

The sample size was calculated to be 60 at 90% power, 5% significance, 20% closure rate difference and allowing for 10% loss to follow up.

The data analysis was performed according to intention-to-treat principle. Mean ± SD was used for presentation of continuous variables and percentages for discrete variables. A two-sided independent sample t test was used for comparison of continuous variables. For discrete variables comparison, chi-square test or Fisher’s exact test was performed. Rank sum test was used for rank data. Data analysis was performed using SPSS version 22 (SPSS Inc., Chicago, IL, USA). A p value of <0.05 was considered statistically significant.

Results

Demographics and clinical features

A total of 69 patients were screened for the study and 9 were screened out. Then 60 patients were enrolled with 2 withdrew and 1 lost to follow up. Finally, 57 patients finished the study with 28 in MOCA group and 29 in EVLA group (Figure 1)

Figure 1.

Flow chart for patient selection process MOCA, mechanochemical ablation; EVLA, endovenous laser ablation.

The mean age was 51.95 ± 10.62 years and 14 were male gender. The CEAP classification for most patients was C3 (52.6%). The demographics and clinical features were shown in Table 1. The median preoperative VCSS was 4.5 (IQR 3–5.75) and 4 (IQR 3–6.5) in MOCA and EVLA group, respectively. The median preoperative VAS was 1 (IQR 1–2.75) and 3 (IQR 1–4) in MOCA and EVLA group, respectively.

Table 1.

demographics and clinical features.

	MOCA	EVLA	p value	All patient
No.	28	29		57
Age	49.96 ± 11.93	53.86 ± 8.98	0.168	51.95 ± 10.62
Gender male/female	11/17	13/16	0.672	14/33
CEAP classification			0.527
C2	5	3		8
C3	13	17		30
C4	10	7		17
C5	0	1		1
C6	0	1		1
GSV reflux time
1–3 s	3	7		10
3–5 s	7	4		11
>5 s	18	18		36
Initial VCSS score	Median 4.5 (IQR 3-5.75)	Median 4 (IQR 3-6.5)
Diameter, mm
2 cm below SFJ	6.34 ± 1.08	5.98 ± 1.39	0.291	6.16 ± 1.25
2 cm below the knee	4.94 ± 1.69	4.48 ± 1.68	0.301	4.71 ± 1.69

MOCA, mechanochemical ablation; EVLA, endovenous laser ablation; CEAP, clinical-etiology-anatomic-pathophysiologic; GSV, great saphenous vein; VCSS, venous clinical severity score; SFJ, saphenous femoral junction.

Procedural details

A typical MOCA procedure was shown in Figure 2. Technical success was achieved in 100% of the patients in both MOCA and EVLA group. No device defect occurred. All GSV main trunk appeared to be occluded on ultrasound scan just after the procedure. Additional ambulatory phlebectomy was carried out in 73.68% (42/57) of the patients, with 71.43% (20/28) in MOCA group and 75.86% (22/29) in EVLA group, respectively. Additional 1% polidocanol foam injection for varicosities was carried out in 87.72% (50/57) of the patients, with 89.29% (25/28) in MOCA group and 86.21% (25/29) in EVLA group, respectively.

Figure 2.

The typical MOCA procedure MOCA, mechanochemical ablation; SFJ, saphenous femoral junction; GSV, great saphenous vein. (a) the new domestic mechanochemical ablation device. (b) preoperative ultrasound confirmed severe SFJ reflux (left) and the GSV puncture point (right). (c) ultrasound confirmed catheter tip and SFJ (left). The tip should be pulled back about 2 cm below SFJ when starting ablation (right). (d) no reflux at SFJ (left) and GSV spasm (right) immediately after MOCA procedure. (e) 3-day follow-up showed no reflux at SFJ (left) and GSV occlusion (right). (f) 6-month follow-up showed no reflux at SFJ (left) and GSV occlusion (right).

Endpoints

The procedures were well tolerated, the post-operative VAS score (1 day after the procedure) was 0 for 26 patients and 1 for 2 patients in MOCA group, 0 for 24 patients and 1 for 5 patients in EVLA group. All the 57 patients finished 6-month follow-up. The GSV main trunk closure rate was 85.71% (24/28) in MOCA group and 96.55% (28/29) in EVLA group (p = .194), respectively. Though recanalized, 2 patients in MOCA group and 1 in EVLA group present with no reflux and symptom. 2 patients in MOCA group present with > 4s reflux but no symptom.

Significant changes were observed in regard of VCSS and CIVIQ at 6-month follow-up. The 6-month post-operative VCSS was 0 for 22 patients, 1 for 4 patients, 2 for 1 patient, and 3 for 1 patient in MOCA group; 0 for 22 patients, 1 for 4 patients, 2 for 1 patient, 3 for 1 patient, and 4 for 1 patient in EVLA group. The 6-month post-operative CIVIQ score was 20.64 ± 1.25 in MOCA group and 20.31 ± 1.00 in EVLA group (p = .273), respectively (Table 2).

Table 2.

Outcomes.

	MOCA	EVLA	p Value
No.	28	29
Preoperative CIVIQ	30.43 ± 7.13	30.03 ± 13.14	0.206
Post-operative CIVIQ at 6-month	20.64 ± 1.25	20.31 ± 1.00	0.273
Closure rate at 6-month	85.71%	96.55%	0.194

MOCA, mechanochemical ablation; EVLA, endovenous laser ablation.

VAS, visual analogue scale; CIVIQ, chronic venous insufficiency questionnaire.

Complications

The vital signs and laboratory tests showed both procedures were safe. Skin paresthesia occurred in 0 in MOCA group and 5 in EVLA group. 1 patient in MOCA group suffered from femoral vein mural thrombosis 3 days after the surgery and was treated with Rivaroxaban. The thrombus disappeared in 2 weeks One patient in EVLA group was discovered with posterior tibial vein thrombosis at 6-month ultrasound follow-up, but the patient has no symptom, and no treatment is required. 1-year ultrasound showed that the posterior tibial vein thrombosis remained stable. Local ecchymosis was observed in 10.71% (3/28) in MOCA group and 13.79% (4/29) in EVLA group, respectively. The ecchymosis all resolved in 7 days without any treatment.

Discussion

Endovascular treatment for varicose veins has emerged as an effective and safe therapeutic strategy in the past decades.¹⁰ Endothermal ablation (ETA) including EVLA and radiofrequency ablation (RFA) has been recommended as the first choice based on large amount of clinical data.¹¹

Compared with traditional surgery, EVT was minimally invasive. However, complications such as thermal damage to superficial nerve appears to be potentially possible, especially for small saphenous veins.^12–14 The injection of tumescent local anesthesia fluid also prolonged the operation time and need additional puncture. In an attempt to avoid these complications and unnecessary puncture, non-thermal non-tumescent ablation including foam sclerotherapy, MOCA and cyanoacrylate vein ablation (CAVA) have been introduced.⁹ MOCA combined mechanical injury and sclerosant injury to the vein wall. An ex vivo study showed that MOCA can cause both endothelium damage and media tearing, the damage of endothelium was significantly increased by MOCA when compared with mechanical ablation or sclerosant alone.¹⁵

Previously, Vähäaho et al¹⁶ reported that the 3-year closure rate of MOCA was 80%, Kim et al reported 92% at 2-year,¹⁷ and Witte reported 87% at 3-year.¹⁸ In the study carried out by Vähäaho et al.,^16,19 the device rotation speed was 3500 r.p.m and 1.5% liquid sodium tetradecyl sulphate was used as sclerosant. They also carried out phlebectomy with small incision. The 1-year closure rate of MOCA was 82%, as a comparison, the 1-year and 3-year closure rate of EVLA or RFA was both 100%. Another meta-analysis²⁰ showed that the efficacy of MOCA in the mid-term period for VCSS improvement and GSV closure rates was inferior than EVLA or RFA. In the present study population, technical success was achieved in 100% of the patients and the GSV closure rate was 85.71% in MOCA group at 6-month. The anatomical closure rate also seems lower in MOCA group; however, no symptom recurrence occurred in the 4 recanalized patients and no further treatment was needed.

The closure rate may also be affected the sclerosant. Polidocanol is the only available option in China, Sodium tetradecyl sulfate may cause more endothelial and media damage compared with polidocanol.²¹ It is reported that change the sclerosant to sodium tetradecyl sulfate and treat the proximal GSV twice may increase the closure rate.^22–23

The CIVIQ score in both MOCA and EVLA group were significantly decreased postoperatively, which showed that the quality of life improved significantly. Less postoperative pain was reported after MOCA than ETA.²² The compliance to MOCA procedure also has been reported to be superior than ETA.²⁴ In our study series, the post-operative VAS score showed less pain present in MOCA group than in EVLA group.

In the present study, ambulatory phlebectomy also may cause cutaneous nerve injury. 5 local skin paresthesia occurred in EVLA group, it’s hard to distinguish whether it is caused by heat-induced tissue injury or local phlebectomy. Nerve injury was quite rare in EVLA. All these skin paresthesia alleviated at 6-month follow-up.

One of the major barriers to the prior MOCA device was the cost. Because this is a pre-marketing study, the cost of the MOCA device is not yet confirmed. As this device is domestic, we think that the price might be cheaper. The application of more similar device will popularize the MOCA technique.

Several limitations may exist in this study. First, the concomitantly performed ambulatory phlebectomy and foam sclerotherapy may increase technical success rate because the potential outflow veins for a GSV at risk for recanalization are closed. Second, the length of treated GSV main trunk was not recorded, thus made the relevant analysis deficient. Third, the follow up time was relatively short, the sample size was relatively small and it was only our preliminary experience.

Conclusion

The new domestic MOCA device is safe and effective in treating primary great saphenous vein reflux. The 6-month closure rate is non-inferior compared with EVLA. However, the long-term results need further follow up.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National High Level Hospital Clinical Research Funding (2023-NHLHCRF-YYPPLC-TJ-26); Elite Medical Professionals Project of China-Japan Friendship Hospital (ZRJY2021-QM13).

ORCID iD

Zhidong Ye

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