Efficacy of Antistax® in Improving Microcirculation of the Skin in the Leg in Patients Suffering From Chronic Venous Insufficiency

Study Overview
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Brief Summary
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Study to determine the efficacy and safety of Antistax® film coated tablets in improving microcirculation of the skin in the leg of patients with chronic venous insufficiency (CVI)

Official Title
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A 17 Week, Randomised, Double-blind, Placebo Controlled Cross-over Trial to Evaluate the Efficacy of Antistax® Film Coated Tablets (Extr. Vitis Vinifera Siccum), 360 mg/Day p.o. in Improving Microcirculation of the Skin in the Leg of Male and Female Patients Suffering From Chronic Venous Insufficiency

Conditions
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Venous Insufficiency

Intervention / Treatment
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* Drug: Antistax®
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female >= 18 years of age CVI I or CVI II (without expanded trophic disturbances) Willing and able to give written informed consent in accordance to Good Clinical Practice and local legislation prior to participation in the study Exclusion Criteria: Concomitant disease(s) exclusion criteria: Decompensated cardiac insufficiency Edema not due to venous disease of the legs (e.g. latent cardiac insufficiency, renal insufficiency, lymph edema, etc) Peripheral arterial disease (ankle/arm pressure index < 0.9) Current acute phlebitis or thrombosis Renal insufficiency (Serum creatinine > 1.5 mg/dl) Liver disease (SGPT (ALAT) > 3x upper limit of normal) Other diseases: insulin-dependent diabetes mellitus, neuropathies, hyper- or hypocalcaemia, malignancies Anamnestic indications of diabetic microangiopathy or polyneuropathy Drug and/or alcohol abuse Pregnant or nursing women or inadequate birth control methods (this applies to females of childbearing potential only) Severe climacteric complaints or changes in, or initiation with post-menopausal hormone replacement therapy within the last 3 months Immobility Avalvulie Klippel-Trénaunay-Weber-Syndrome (Naevus varicosis osteohypertrophicus, Haemangiectasia hypertrophicans) State after pulmonary embolism Recognized hypersensitivity to the trial drug ingredients Current florid venous ulcus Clinical indication for a necessary, specific phlebologic acute treatment, e.g. compressive treatment, phlebectomy, etc. Previous treatment(s) exclusion criteria: Treatment with venous drugs within the last 4 weeks Changes in, or initiation with, treatment with theophylline, diuretics, cardiac glycosides, ACE inhibitors or calcium antagonists within the last 8 days Concomitant treatment/non-drug therapy exclusion criteria: Other venous drugs apart from the trial medication Compression bandages Venous surgery of the leg used for the fluxmetry Extensive use (i.e. on more than a total of 6 days during the entire trial) of laxatives which affect fluid or electrolyte balance Major surgery requiring full anesthesia Other exclusion criteria: Previously studied under this protocol Participation in another clinical trial within the previous 90 days or during the present study 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 a 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antistax®<br>1 x 360 mg for 42 days | Drug: Antistax®<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in the resting flux | measured in the frequency range 10-37 kHz on the skin of the inside lower leg using the Laser Doppler Fluxmetry | Baseline, after 6 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in the resting flux | measured in the frequency range 10-37 kHz | Baseline, after 3 weeks of treatment | 
| Changes in the resting flux | measured in the frequency range <10 kHz | Baseline, after 3 and 6 weeks of treatment | 
| Changes in the combined resting fluxes (<37 kHz) |  | Baseline, after 3 and 6 weeks of treatment | 
| Changes in the transcutaneous oximetry (TcPO2) | measured on the inside lower leg of the more CVI-affected leg | Baseline, after 3 and 6 weeks of treatment | 
| Change from baseline in the calf circumference of the most affected leg |  | Baseline, after 3 and 6 weeks of treatment | 
| Change from baseline in the ankle circumference of the most affected leg |  | Baseline, after 3 and 6 weeks of treatment | 
| Change from baseline in the subjective symptoms of CVI measured by Visual Analogue Scales (VAS) |  | Baseline, after 3 and 6 weeks of treatment | 
| Global efficacy assessment by patient on a 4-point verbal rating scale (VRS) |  | after 6 weeks of treatment | 
| Global efficacy assessment by investigator on a 4-point VRS |  | after 6 weeks of treatment | 
| Number of patients with adverse events |  | up to 16 weeks | 
| Number of patients with clinically relevant changes in laboratory values |  | Baseline, up to 16 weeks | 
| Number of patients with clinically significant changes in vital signs |  | Baseline, up to 16 weeks | 
| Global tolerability assessment by investigator on a 4-point VRS |  | after 6 weeks of treatment | 
| Global tolerability assessment by patient on a 4-point VRS |  | after 6 weeks of treatment |