Management of Endothelial Dysfunction in Patients With Chronic Venous Insufficiency After Endovenous Surgical Procedure
Condition: Venous Insufficiency of Leg; Venous Insufficiency (Chronic)(Peripheral); Endothelial Dysfunction
MeSH terms: Venous Insufficiency
Study type: Interventional

Summary: 
      Endothelial dysfunction is assessed in patients with chronic venous insufficiency of lower
      limbs (grade C4 according to C - clinical manifestations, E - etiologic factors, A - anatomic
      distribution of disease, and P - underlying pathophysiologic findings (CEAP) classification)
      prior to and after endovenous surgical procedure, i.e. endovenous laser ablation of great
      saphenous vein, microphlebectomy of varicose branches. Two treatment groups (with and without
      additional pharmacotherapy) are compared.
    

Detailed description: 
      Each patient will be examined 4 times:

      Visit 1 (day -1)

        -  collecting and documenting patients' complaints and medical history

        -  local examination

        -  ultrasound angiography of the lower limbs veins

        -  assessment of clinical grade according to CEAP classification

      Visit 2 (day 0)

        -  assessment of venous disease severity according to Venous Clinical Severity Score (VCSS)

        -  assessment of quality of life with Chronic Venous Insufficiency Quality of Life
           Questionnaire (CIVIQ-20)

        -  assessment of clinical grade according to CEAP classification

        -  measurement of microcirculation in the operated limb by laser flowmetry using portable
           device (laser Doppler flowmetry (LDF) registration will be performed on leg anterior
           surface (lower third) for 10 minutes)

        -  assesment of blood laboratory parameters of endothelial dysfunction: homocysteine, von
           Willebrand factor, plasminogen activator inhibitor-1 (PAI-1), E-selectin, P-selectin,
           soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular endothelial cell
           adhesion molecule-1 (sVCAM-1)

        -  flow cytometry analysis of circulating cells expressing surface markers (clusters of
           differentiation (CD)): CD 45-, CD 34+, CD 146+, CD 31+, CD 105+ and CD 309+

        -  surgical treatment is performed as endovenous laser ablation of GSV and microphlebectomy
           of varicose branches according to a standard protocol

        -  patients' randomization (method of random numbers) into 2 treatment groups of 20
           subjects each with sulodexide treatment (250 LSU bid for 30 day) for the active
           treatment group and without any additional pharmacotherapy for the control group

      Visit 3 (day 4 after intervention)

      - ultrasound angiography of the operated limb (evaluation of the venous ablation and
      examination of endothermal heat-induced thrombosis (EHIT))

      Visit 4 (day 32 after intervention)

        -  collecting and documenting patients' complaints

        -  local examination

        -  ultrasound angiography of the lower limbs veins

        -  assessment of clinical grade according to CEAP classification

        -  assessment of venous disease severity according to VCSS

        -  assessment of quality of life with CIVIQ-20

        -  measurement of microcirculation in the operated limb by laser flowmetry using portable
           device

        -  assesment of blood laboratory parameters of endothelial dysfunction: homocysteine, von
           Willebrand factor, PAI-1, E-selectin, P-selectin, sICAM-1, sVCAM-1

        -  flow cytometry analysis of circulating cells expressing surface markers: CD 45-, CD 34+,
           CD 146+, CD 31+, CD 105+ and CD 309+
    

Intervention name(s): Endovenous laser ablation of great saphenous vein (GSV) and microphlebectomy of varicose veins; Pharmacotherapy
Intervention type(s): Procedure; Drug
Intervention description(s): Surgical treatment is performed as endovenous laser ablation of GSV and microphlebectomy of varicose branches according to a standard protocol:
The intervention includes treatment of the pathological upright reflux and varicose veins. Ultrasound-guided GSV puncture at the upper third of the leg under local anesthesia. The light guide is inserted into the vein lumen and pushed through to the saphenofemoral junction. Under ultrasound guidance the light guide is positioned at v. epigastrica superficialis junction. Under ultrasound guidance tumescent anesthesia is produced around the GSV from puncture site up to the saphenofemoral junction. Laser coagulation (with radial light guide), linear energy density - 75 J/cm, automatic traction of the light guide at the speed 0.7 mm/sec. Varicose veins are resected through skin punctures using Varady hook 1-2 mm.; After surgical intervention the active treatment group will receive sulodexide 250 lipasemic units (LSU) bid for 30 days.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science