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

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

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)

Study Overview

• Status: Completed
• Conditions: Venous Insufficiency
• Intervention / Treatment: Drug: Placebo; Drug: Antistax®

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: Antistax®; 1 x 360 mg for 42 days	Drug: Antistax®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Martinez-Zapata MJ, Vernooij RW, Simancas-Racines D, Uriona Tuma SM, Stein AT, Moreno Carriles RMM, Vargas E, Bonfill Cosp X. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 2020 Nov 3;11(11):CD003229. doi: 10.1002/14651858.CD003229.pub4.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2002
• Primary Completion (Actual): August 1, 2002

Study Registration Dates

• First Submitted: July 15, 2014
• First Submitted That Met QC Criteria: July 15, 2014
• First Posted (Estimate): July 16, 2014

Study Record Updates

• Last Update Posted (Estimate): July 16, 2014
• Last Update Submitted That Met QC Criteria: July 15, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Venous Insufficiency
• Other Study ID Numbers: 1138.3