Efficacy and Tolerability of Venoactive Drugs in Patients With Chronic Venous Diseases C4a&b in Real Clinical Practice.

The study is aimed at evaluating the efficacy and tolerability of systemic pharmacotherapy as a part of combination treatment, and its influence on the overall treatment outcomes in patients with skin changes (CEAP class C4a and C4b).

Primary goal:

To study the efficacy of systemic pharmacotherapy as part of combination therapy and its impact on the:

* thickness of the skin-fat fold (ultrasound examination);
* change in the venous clinical severity score (VCSS);
* change in the CEAP clinical class of CVD;
* evolution of CVD symptoms characteristic for CEAP class C4 (sensations of skin tightening, burning, itching, pain, and exudation) using the Visual Analogue Scale (VAS).

Secondary goals:

1. To study the efficacy of systemic pharmacotherapy as part of combination therapy and its impact on the:

   * area of affected skin determined by curvimetry technique (only in selected centers that use this technique routinely) before and after the treatment in patients with skin changes of CEAP class C4a or C4b in real clinical practice;
   * skin density determined by durometry technique (only in selected centers that use this technique routinely).
2. To evaluate the changes in the quality of life using the CIVIQ-14 questionnaire (global index score \[GIS\]) .
3. To study the tolerability of systemic pharmacotherapy as part of combination therapy in patients with skin changes of CEAP class C4a or C4b.

Eligibility Criteria:
Inclusion Criteria:

* Age 18 years old or above
* Written informed consent
* Patient did not receive treatment with venoactive drugs within the past 4 -weeks prior to the inclusion in the study
* Diagnosis of chronic venous disease of CEAP class C4
* No surgical intervention for CVD is planned by a doctor

Exclusion Criteria:

* Chronic venous disease of СЕАР class C0-С3 or class С4-С6
* History of alcohol or drug abuse or use of narcotic drugs
* Peripheral artery disease
* Lymphatic edema of the lower extremities
* Secondary varicose veins, angiodysplasia, or neoplasia
* Arterial disease (ankle-brachial index \<0.9)
* Infection within the past 6 weeks
* Any of the following concomitant diseases, which can affect the results:
* Connective tissue disease (including rheumatoid arthritis), arthritis
* Heart failure
* Chronic kidney disease
* Decompensated diabetes mellitus
* Skin diseases of non-venous origin
* Intermittent claudication (peripheral artery disease)
* Diseases of the bones or joints of the lower extremities
* Malignancy

Treatment with drugs potentially causing leg edema (calcium channel blockers, hormonal drugs, NSAIDs, etc.) History of deep vein thrombosis (within the past year) History of superficial thrombophlebitis (within the past 3 months) History of surgical intervention (within the past 3 months) Patient cannot walk (regardless of the cause) Predictable poor adherence to treatment Participation of a patient in the intervention study within the previous 3 months For women: pregnancy or breastfeeding, the desire to become pregnant within at least 2 months after the study Patients with a contraindication to diosmin-containing agents, including Detralex Patient uses the topical treatments contraindicated in case of skin integrity violation.