Assess the Efficacy and Tolerability of Antistax Film-coated Tablets in Patients With Chronic Venous Insufficiency

Study Overview
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Brief Summary
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To assess the efficacy and tolerability of Antistax film coated tablets in patients with chronic venous insufficiency (CVI, CEAP Classification: Clinical class 3 and 4a).

Official Title
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A 12-week, Double-blind, Randomised, Placebo-controlled, Multicentre Trial to Evaluate Efficacy and Tolerability of Antistax® Film Coated Tablets, 720 mg/Day Orally, in Male and Female Patients Suffering From Chronic Venous Insufficiency

Conditions
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Venous Insufficiency

Intervention / Treatment
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* Drug: Red vine leaf extract (AS 195)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female 18 years of age or older CVI, Clinical Class 3 and Class 4a according to the CEAP classification Presence of stable edema determined by a pretibial pit after 30 seconds pressure with the thumb documented by a photo Stable and reproducible status of swelling documented by difference of less than 150g between screening and baseline as determined by water displacement method Presence of moderate to severe varicoses (dilated, tortuous veins in the subcutaneous tissue with a diameter of more than 3mm Intensity of leg pain at least 5 cm on the Visual Analogue Scale at baseline and presence of hyperpigmentation or eczema and presence of moderate to severe edema Willing and able to give written informed consent prior to participation in the trial Patients expected to be compliant (compliance with run-in medication greater than 80% as checked by drug count) Exclusion Criteria: Decompensated cardiac insufficiency according to the New York Heart Association (NYHA) classification III and IV for cardiac patients Edema not due to venous disease of the legs(e.g. latent cardiac insufficiency, renal insufficiency, lymphoedema, etc) Severe skin changes, e.g. lipodermatosclerosis Current florid venous ulcer Peripheral arterial disease (ankle/arm pressure index less than 0.9) Untreated or insufficiently controlled hypertension Current acute phlebitis of thrombosis with the last 3 months. Post-thrombotic syndrome, who do not currently receive an anticoagulation treatment can be included in the trial Renal insufficiency Liver disease; hepatic insufficiency Hyper- or hypocalcemia Malignancies Anamnestic indications of diabetic microangiopathy or polyneuropathy Drug and/or alcohol abuse Severe climacteric complaints; changes in or initiation of post-menopausal hormone replacement therapy within the last 3 months Immobility Avalvulia Klippel-Trénaunay-Weber-Syndrome State after pulmonary embolism Recognized hypersensitivity to the trial drug ingredients Clinical indication for a specific phlebologic treatment, e.g. compression treatment phlebectomy, etc Previous Treatments: Compression therapy and/or wearing of support stockings less than 2 weeks prior to the visit at baseline Venous surgery or sclerotherapy with the last 3 months at the leg used for volumetry Treatment with drugs affecting the veins less than 4 weeks prior to visit 1 Changes in or unstable response to treatment with theophylline, cardiac glycosides, ACE-inhibitors, calcium antagonists, or laxatives with the last 2 weeks prior to visit 1 Concomitant Treatment: Compression therapy Diuretics Nitrates Ergot alkaloids All preparations which are used as compounds for venous therapy in CVI (e.g. vasoprotectives for antivaricose therapy, preparations with heparin, sclerosing agents, flavonoid-containing preparations, other phytopharmaceuticals Other drugs active on blood vessels and circulation Extensive use of laxatives Anticipated changes in the intake of hormones, ie contraceptives Scheduled major surgery requiring full anesthesia Other exclusion Criteria: Previously studied under the present protocol Participation in another clinical trial within less than 90 days prior to Visit 1 Participation in another clinical trial during the present trial Patient is investigator, co-investigator, trial nurse in this trial or is a relative of the investigator, co-investigator or trial nurse in this trial Pregnant or nursing women or inadequate birth control methods (this applies to females of childbearing potential only; reliable contraceptive methods are hormonal contraceptives, intrauterine devices, sexual abstinence of sterilization) Patients considered as mentally ill as well as unable to work or with limited working ability, or unable (or only partially able) to follow the spoken or written explanations concerning the trial Patients in bad general health state according to the investigator's judgment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Antistax film-coated tablets 360 mg<br>Patient to receive 2 tablets daily as a morning dose, each containing 360 mg Antistax | Drug: Red vine leaf extract (AS 195)<br>* Antistax film-coated tablet 360 mg<br>|
| Placebo Comparator: Placebo<br>Patient to receive 2 tablets identical to those containing 360 mg Antistax daily as a morning dose | Drug: Placebo<br>* Placebo tablets identical to those containing Anstistax 360 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in limb volume determination at day 84 (water displacement method) |  | 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in limb volume determination at day 21 and 42 (water displacement method) |  | 21 and 42 days | 
| Change from baseline in the subjective symptoms of CVI (tired, heavy legs, sensation of tension in the legs) pain in the legs) measured by Visual Analogue Scales at day 21,42 and 84 |  | 21, 42 and 84 days | 
| Incidence of adverse events |  | 84 days | 
| Global assessment of efficacy by the patient at day 84 |  | 84 days | 
| Change from baseline in the calf circumference at day 21, 42 and 84 |  | 21, 42 and 84 days | 
| Global assessment of efficacy by the investigator at day 84 |  | 84 days | 
| Time to improvement in symptoms |  | 84 days | 
| Vital signs (pulse rate, blood pressure) |  | 84 days | 
| Number of patients with abnormal Serum Laboratory Parameters |  | 84 days | 
| Global assessment of tolerability by the patient at day 84 |  | 84 days | 
| Global assessment of tolerability by the investigator at day 84 |  | 84 days |