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).
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.