Efficacy and Safety of Coumarin and Troxerutin in the Symptomatic Treatment of Chronic Venous Insufficiency
Condition: Chronic Venous Insufficiency
MeSH terms: Venous Insufficiency
Intervention: Coumarin/troxerutin; Placebo
Intervention description: Coumarin + troxerutin fixed-dose combination tablets; Coumarin + troxerutin placebo-matching tablets
Intervention MeSH terms: Troxerutin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 829.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purpose of this study is to evaluate the efficacy and safety of the fixed-dose
      combination of coumarin and troxerutin versus placebo in the symptomatic treatment of chronic
      venous insufficiency.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Consent of subject or legal representative

          2. Men or women of any ethnicity, aged between 18 and 75 years, and body mass index (BMI)
             equal or less than 40.

          3. Is able to use properly the medication according to protocol.

          4. Has chronic venous insufficiency in the reference leg with the clinical classification
             C3, or C4a orC4b or C5, provided that in two last situations the present
             lipodermatosclerosis does not compromise more than 1/3 portion of the leg immersed or
             immersible in the plethysmometer.

          5. Has stable edema (in a steady state), equivalent to a variation lower than or equal to
             10% in partial volume of the reference leg between the screening visit and the
             randomization visit, and present for at least 6 months.

          6. Scoring in "Severity Score of Local Complaints" equal to or higher than 5 total
             points.

          7. Women who are using an effective (at the discretion of the investigator), but not
             hormonal, birth control method (not hormonal intrauterine device (IUD), surgical
             sterilization, among others), or who are postmenopausal, in addition to condom use
             (mandatory).

        Exclusion Criteria:

          1. Has chronic venous insufficiency classified as C1, C2 in the reference leg or C6 in
             any leg.

          2. Has chronic venous insufficiency C4b or C5 in the reference leg, with
             lipodermatosclerosis present in more than 1/3 portion of the leg immersed in the
             plethysmometer.

          3. Has unstable edema, equivalent to variation of more than 10% of partial volume in the
             reference leg between the screening visit and randomization visit, prior to start of
             treatment.

          4. Has venous obstruction and/or deep vein thrombosis (DVT) and/or presence of phlebitis
             in lower limbs during the last 3 (three) months.

          5. Has developed deep vein insufficiency during the last 3 (three) months.

          6. Has other diseases that may interfere in the findings of the study such as:
             lymphedema, thrombosis, clotting disorders, edema of lower limbs due to right-sided
             heart failure, arterial obstruction of lower limbs and other conditions that, at
             medical discretion, are relevant to exclusion, particularly symptoms which are similar
             to the symptomatology of chronic venous insufficiency.

          7. Has a history of surgery at the venous system or sclerotherapy or who received any
             treatment for chronic venous insufficiency during the last 03 months, whether it was
             by drug, elastic stocking, laser, or surgery.

          8. Has used previously Venalot® and had no benefits with the treatment.

          9. Has a previous history of known or suspected allergy or intolerance to any of the
             ingredients of the medicinal product under investigation.

         10. Has any clinical finding (history and physical examination) that is interpreted by the
             physician-investigator as a risk to participant's participation in the study.

         11. Has known serious systemic disease, according to the medical and/or laboratory
             history.

         12. Has history of a known liver disease such as hepatitis A, hepatitis B, or C.

         13. Has changed at least one lab parameters: aspartate aminotransferase (AST), alanine
             aminotransferase (ALT), gamma-glutamyltransferase (gamma-GT), or alkaline phosphatase
             2.5 times above the upper limit of normal range; hemoglobin less than 10 g/dL;
             clearance of creatinine estimative equal or above 60mL/min/1.73 m^2; platelets below
             90,000/mL; and total bilirubin and fractions 1.5 times above the normal values.

         14. Has been using diuretics for a period less than or equal to 6 months due to any
             disease (hypertension, renal failure, or other).

         15. Has serious chronic liver or kidney disease, according to the medical and/or
             laboratory history.

         16. Has uncontrolled blood hypertension (systolic blood pressure > 180 mmHg or diastolic
             blood pressure > 100 mmHg) at randomization or clinical hypertensive urgency.

         17. Has a previous history of diabetes mellitus on use of insulin.

         18. Has received treatment with immunosuppressive drugs, including systemic
             corticosteroids within 30 days before the start of study (randomization visit), or who
             are receiving immunosuppressive treatments, or who have known congenital or acquired
             immunodeficiency.

         19. Has malignant neoplasms, from any etiology, or who are receiving any type of
             anticancer treatment, unless when properly treated and with no evidence of recurrence
             during the last five years. Non-melanoma skin cancer is not an exclusion criterion.

         20. Is unable to understand the guidelines specified in this protocol or who cannot attend
             all the study visits.

         21. Has a previous history of alcoholism, drug abuse, psychological or emotional problems
             in the last 5 years that can invalidate the Informed Consent Form or restrain
             participant's ability to comply with the requirements of the protocol.

         22. Pregnant or breastfeeding women, or those who have the potential to become pregnant
             and are not using an appropriate contraceptive method.

         23. Women who are using hormonal contraceptives or hormone replacement treatment,
             including phytoestrogens, within the last 3 months.

         24. Took part in clinical trials during the last year.