Sulodexide in the Treatment of Chronic Primary Venous Disease of the Lower Extremities

Inclusion Criteria:

• Diagnosed primary venous disease of the lower limbs in stage C2 - C6 according to theCEAP classification, clinical involvement of the venous system of the lower limbs isverified by duplex ultrasonography
• Presence of objective and subjective symptoms of the disease (classified according torVCSS score ≥ 4)
• At the time of the enrolment, patient is not using nor planning to use compressiontherapy from his own decision or the decision of the treating physician
• The patient signed an informed consent for inclusion in the clinical trial and consentto the processing of personal data
• Patient over 18 years of age
• Male or female patient of non-childbearing potential, i.e.: post-menopausal (at least 2 years without spontaneous menses) or surgically sterile (bilateral tubal occlusionor hysterectomy or ablation of both ovaries); OR of childbearing potential but with anegative pregnancy test result at Visit 1 AND agrees to use a highly effective methodof contraception

Exclusion Criteria:

• Use of a drug with venoactive effect in the last month
• Regular use of compression therapy or use of mechanical devices for reduction ofoedema in the last month
• Heart Failure as per NYHA III and IV, congestive heart failure with peripheral oedemas
• Chronic kidney disease with GF < 30 ml/min (< 0,5 ml/s) and/or proteinuria > 0,5 g/24hours, nephrotic syndrome, renal oedemas
• Advanced liver disease (Child-Pugh B and C or laboratory values of ALT or AST morethan 3 times upper limit of normal range)
• Deep venous thrombosis lower limb thrombosis and / or documented residual venousobstruction or deep venous reflux due to post-thrombotic changes in the deep venoussystem
• Superficial venous thrombosis of the lower limbs in the previous 6 months
• Congenital venous / venolymphatic venous malformation
• Neuropathy of any aetiology
• Diabetic foot syndrome
• Refractory (uncontrollable) arterial hypertension (inability to achievetherapeutically systolic blood pressure ≤ 160 mmHg or diastolic blood pressure ≤ 100mmHg)
• Symptomatic ischemic disease of lower limbs
• Lymphoedema: primary, posttraumatic, postoperative, post-radiation, malignant
• Manual/instrumental lymphatic drainage in the last 6 months
• Invasive procedure on the lower limbs in the last 6 months
• Trauma of the lower extremity that has not fully healed
• Use of oral/parenteral anticoagulants, dual antiplatelet therapy, diuretics,corticosteroids, oestrogens, or progesterone and its derivates
• Chronic pain treatment ≥ 14 days
• Psychopharmaceuticals affecting fluid retention (antipsychotics, combinedantidepressants)
• Pathologic obesity (BMI > 40 kg/m2)
• The patient is currently enrolled in another interventional or non-interventionalstudy
• Contraindications to the administration of sulodexide according to IB (haemorrhagicdiathesis, hypersensitivity to the drug substance or any of the excipients, heparin,heparinoids or other glycosaminoglycans (GAGs), etc.)
• Patients with active malignant disease or malignant disease in remission for less than 5 years
• Pregnancy
• Breastfeeding Continuous exclusion criteria:
• Clinically significant progression of the investigated condition, which requiresurgent or early invasive therapy (as assessed by the investigating physician)
• Onset of any condition requiring initiation of the not permitted medication/treatment
• Serious adverse reactions
• Pregnancy Compression therapy can be initiated anytime during the trial participation in case thatpatient experiences worsening of the rVCSS score of at least 4 points compared to baselineAND the treating physician decides to prescribe such regimen. Certified/notifiedcompression stockings of class II (23-32 mmHg) based on circular knit are allowed. Patientsinitiating compression therapy are not excluded but the stocking need to be taken off a daybefore the scheduled study visit. The treatment allocation in patients initiatingcompression therapy remain blinded. In case compression therapy is initiated during study participation, information about thedate of initiation, type and adherence is collected in the following visits. If sufficient proportion of subjects is switched to compression therapy, compressiontherapy will be tested as effect modifier across CEAP classes.