Efficacy and tolerability of a red-vine-leaf extract in patients suffering from chronic venous insufficiency--results of a double-blind placebo-controlled study.
OBJECTIVE
The aim of this study was to investigate the effect of a red-vine-leaf extract (AS195, Antistax(®), Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany) on the volume of the leg and clinical symptoms in patients with chronic venous insufficiency (CVI).


METHODS
A multicentre, randomised, double-blind and placebo-controlled study was carried out with 720 mg AS195 per day over 12 weeks in CVI patients (CEAP Grades 3-4a) and moderate-to-severe clinical symptoms. Efficacy endpoints were changes in limb volume determined by water displacement volumetry, clinical CVI symptoms assessed on a 10-cm visual analogue scale and global efficacy evaluations.


RESULTS
The full-analysis set included 248 patients (placebo: n = 122; AS195: n = 126). After 12 weeks, AS195 significantly reduced lower limb volume by a mean of 19.9 standard error (SE) 8.9 ml over placebo (95% confidence interval (CI): -37.5, -2.3; p = 0.0268; analysis of covariance, ANCOVA). The standardised effect size of 0.28 for volume reduction indicates a clinically relevant effect. On Day 84, the symptom of 'pain in the legs' assessed by visual analogue scale decreased in the AS195 group compared with the placebo group: mean difference -6.6 SD 3.3 mm (95% CI: -13.1,-0.1; p = 0.047). Other symptoms showed no significant change. The tolerability of AS195 was similar to that of placebo.


CONCLUSIONS
AS195 treatment for 84 days resulted in an approximately 20 ml reduction of limb volume in the active treatment group compared with the placebo group. Patients reported subjective improvement following treatment with AS195 compared with placebo. However, patients' overall rating of efficacy did not correlate well with measured reductions in limb volume.


BACKGROUND
ClinicalTrials.gov NCT00855179.
Department of Dermatology, University of Bonn, Sigmund-Freud-Strasse 25, 53229 Bonn, Germany. Eberhard.Rabe@ukb.uni-bonn.de
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Rabe
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Stücker
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Esperester
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Schäfer
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Ottillinger
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D004311:Double-Blind Method; D004487:Edema / Q000188:drug therapy / Q000209:etiology; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D010147:Pain Measurement; D015990:Placebo Effect; D010936:Plant Extracts / Q000009:adverse effects / Q000627:therapeutic use*; D018515:Plant Leaves; D011794:Quercetin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013607:Tablets; D013997:Time Factors; D016896:Treatment Outcome; D014689:Venous Insufficiency / Q000150:complications / Q000188:drug therapy*; D027843:Vitis; D055815:Young Adult
C522873:Antistax; D002317:Cardiovascular Agents; D010936:Plant Extracts; D013607:Tablets; D011794:Quercetin