Efficacy, Safety, and Real-World Evidence of VenaSeal™ in the Management (EVOLVE-V) of Varicose Veins: A Prospective Multicenter Study.

Study****Title

 Efficacy, Safety, and Real-World Evidence of VenaSeal™ in the Management of Varicose Veins: A Prospective Multicenter Study

|Background

Varicose veins are the most common manifestation of chronic venous disease (CVD), a spectrum of lower limb venous disorders that collectively account for significant morbidity worldwide.(1) Characterized by dilated, tortuous subcutaneous veins more than or equal 3 mm in diameter, varicose veins most often involve the great saphenous vein (GSV), small saphenous vein (SSV), anterior accessory saphenous vein (ASV), and their tributaries.(2) As the disease progresses, patients may develop edema, skin pigmentation, eczema, lipodermatosclerosis, and, in advanced stages, venous ulceration. These complications extend far beyond cosmetic concerns, often leading to impaired mobility, reduced productivity, and diminished quality of life.(3) Globally, varicose veins affect an estimated 20 to 30% of adults, with prevalence increasing with age.(4) In India, where occupational risk factors such as prolonged standing and heavy manual labor are common, the disease is widespread but frequently under-recognized and under-treated.(5) Consequently, many patients present late, often with advanced complications.

The introduction of Duplex ultrasonography has transformed the

diagnosis of varicose veins by allowing precise mapping of reflux patterns, with superficial axial reflux now recognized as the diagnostic hallmark.(6) These advances in imaging have paved the way for minimally invasive therapies, shifting practice away from conventional surgery. Among these, the VenaSeal closure system represents a novel cyanoacrylate-based technology that permanently occludes incompetent veins under ultrasound guidance. Once delivered into the target vein, the adhesive rapidly polymerizes, coapting the vein walls and leading to fibrosis and eventual resorption of the treated segment. This eliminates reflux by rerouting venous circulation through collateral pathways.(7) Unlike thermal ablation, VenaSeal™ does not require tumescent anesthesia, thermal energy, or perivenous injections, thereby minimizing procedural discomfort, reducing the risk of nerve

injury, and enabling early return to daily activities.(8) International

studies have consistently demonstrated high closure rates, durable efficacy, and favorable safety profiles; however, evidence from Indian patients remains limited. Given the regional variations in venous anatomy, disease presentation, and healthcare-seeking behavior, generating local data is essential.

To address this gap, the present study employs a prospective design. To ensures systematic evaluation under defined protocols. We aim to generate real-world evidence on the efficacy and safety of the VenaSeal closure system in Indian

patients with varicose veins.

|Study****Objective

 ·      Primary Objective: To evaluate the efficacy and safety of VenaSeal™ closure system for GSV, ASV and SSV incompetence through a structured follow up at 1,3 and 6 months.

·      Secondary****Objectives:

 o    To evaluate changes in Venous Clinical Severity Score (VCSS) at follow- up visits.

o    To assess patient-reported quality of life using SF 36.

 o    To analyze time to closure, recanalization, and durability of outcomes.

 o    To characterize adverse events including hypersensitivity and phlebitis.

|Study****Design

Multicentre, Prospective, single arm, observational study

|Study****Sites

10 centers across India handling the management of chronic venous disease.

|Sample****Size

We plan to enroll 400 patients in the prospective

|**Inclusion/**Exclusion Criteria

Inclusion****Criteria

·     Adults aged 21 to 80 years at the time of procedure.

·     Documented reflux (more than 0.5 seconds) GSV, ASV or SSV.

·     Vein diameter up to 12 mm, with a minimum 1 cm skin depth.

·     Presence of one or more symptoms attributable to venous incompetence, including visible dilated veins, pain, swelling, heaviness, pruritus, night cramps, skin changes, or ulceration.

·     CEAP classification C2 to C6.

·     Patient has chosen VenaSeal™ nonthermal, nontumescent endovenous ablation after understanding the risks and benefits of available modalities

·     Willingness to attend follow-up visits and comply with post- procedure compression.

Exclusion****Criteria

·      Prior treatment of the target GSV, ASV, or SSV.

·      Symptomatic peripheral arterial disease with ankle-brachial index (ABI) less than 0.8.

·      History of deep vein thrombosis, pulmonary embolism, or venous aneurysm more than 12 mm.

·      Tortuous target vein not amenable to catheter placement.

·      Known hypersensitivity to cyanoacrylate adhesives or adhesives (skin glue, acrylic nails, eyelash glue, adhesive bandages).

·      Significant autoimmune or systemic inflammatory disorders.

·      History of multiple drug or food allergies.

·      Active psoriasis or atopic dermatitis.

·      Diameter of target vein more than 12 mm in any segment.

·      Patients unwilling/unable to provide informed consent or adhere to follow-up.

|Study****Device

VenaSeal closure system

|Study****Timelines

1.   Prospective enrolment: 5-6 months (Jan 2026-May 2026)

 2.   Follow-up duration per patient: 6 months (May 2026– Nov 2026)

3.   Data analysis & CSR: 2-4 months (Nov 2026 – Jan 2027)

|Primary Endpoints

Duplex-confirmed complete closure of the treated target vein at 1 and 3 months, defined as

absence of flow with no patent segment more than 5 cm on color flow, compression, and pulsed Doppler ultrasound.

|Secondary Endpoints

·       Incidence and characterization of adverse events, including phlebitis, hypersensitivity, and recanalization.

·       Requirement for re-intervention or adjunctive procedures during follow-up.

·       Time to closure and/or recanalization.

 ·       Change in Venous Clinical Severity Score (VCSS) at 1 and 3 months.

 ·       Patient-reported quality of life (QoL) at 3 and 6 months (telephonically), using SF 36.

  

Study****Methodology

This is a multicentre, Prospective, single-arm, observational study designed to evaluate the efficacy and safety of the VenaSeal closure system in Indian patients with varicose veins. The Prospective approach ensures that the study captures real-world practice patterns and providing protocol-driven evaluation with standardized follow- up.

Patients will be enrolled across 10 centres in India that are handling the management of chronic venous disease and performing endovenous interventions. Eligible patients will be categorized into three severity levels; mild, moderate and severe. Diameters of the veins to be treated will be categorized as; 5 to 8 mm, 8 to 10 mm and 10 to 12 mm. Distance of the veins from the skin surface will be recorded. Treatment with Venaseal will be done for unilateral or bilateral limb and the quantity of the glue used will be recorded. Data will be collected at baseline, immediately post-procedure (3 to 7 days), 1 month, 3 months, and 6 months (completely via telephone). These patients will undergo systematic evaluation including duplex ultrasonography pre and post procedure. Venous Clinical Severity Score and quality- of-life assessment (SF36) will be done the follow up visits.

|Statistical****Methodology

Prospective data will be analyzed using both descriptive and inferential methods. Vein closure at 1 and 3 months will be expressed as proportions with 95% confidence intervals, while longitudinal changes in VCSS and quality-of-life scores will be assessed using paired t-tests or repeated measures models, depending on data distribution. Time-to-event outcomes, including closure and recanalization, will be analyzed using survival methods. Adverse events will be summarized descriptively by frequency, severity, and relationship to treatment. Multivariable regression may be used to identify predictors of non-closure or adverse events, with adjustment for prespecified covariates such as age, sex, baseline CEAP class,

and vein diameter.