Clinical trial NCT00855179: Assess the Efficacy and Tolerability of Antistax Film-coated Tablets in Patients With Chronic Venous Insufficiency
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Venous Insufficiency
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-03-04
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

1. Male or Female
2. 18 years of age or older
3. CVI, Clinical Class 3 and Class 4a according to the CEAP classification
4. Presence of stable edema determined by a pretibial pit after 30 seconds pressure with the thumb documented by a photo
5. Stable and reproducible status of swelling documented by difference of less than 150g between screening and baseline as determined by water displacement method
6. Presence of moderate to severe varicoses (dilated, tortuous veins in the subcutaneous tissue with a diameter of more than 3mm
7. 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
8. Willing and able to give written informed consent prior to participation in the trial
9. Patients expected to be compliant (compliance with run-in medication greater than 80% as checked by drug count)

Exclusion Criteria:

1. Decompensated cardiac insufficiency according to the New York Heart Association (NYHA) classification III and IV for cardiac patients
2. Edema not due to venous disease of the legs(e.g. latent cardiac insufficiency, renal insufficiency, lymphoedema, etc)
3. Severe skin changes, e.g. lipodermatosclerosis
4. Current florid venous ulcer
5. Peripheral arterial disease (ankle/arm pressure index less than 0.9)
6. Untreated or insufficiently controlled hypertension
7. 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
8. Renal insufficiency
9. Liver disease; hepatic insufficiency
10. Hyper- or hypocalcemia
11. Malignancies
12. Anamnestic indications of diabetic microangiopathy or polyneuropathy
13. Drug and/or alcohol abuse
14. Severe climacteric complaints; changes in or initiation of post-menopausal hormone replacement therapy within the last 3 months
15. Immobility
16. Avalvulia
17. Klippel-Trénaunay-Weber-Syndrome
18. State after pulmonary embolism
19. Recognized hypersensitivity to the trial drug ingredients
20. Clinical indication for a specific phlebologic treatment, e.g. compression treatment phlebectomy, etc

Previous Treatments:

1. Compression therapy and/or wearing of support stockings less than 2 weeks prior to the visit at baseline
2. Venous surgery or sclerotherapy with the last 3 months at the leg used for volumetry
3. Treatment with drugs affecting the veins less than 4 weeks prior to visit 1
4. 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:

1. Compression therapy
2. Diuretics
3. Nitrates
4. Ergot alkaloids
5. 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
6. Other drugs active on blood vessels and circulation
7. Extensive use of laxatives
8. Anticipated changes in the intake of hormones, ie contraceptives
9. Scheduled major surgery requiring full anesthesia

Other exclusion Criteria:

1. Previously studied under the present protocol
2. Participation in another clinical trial within less than 90 days prior to Visit 1
3. Participation in another clinical trial during the present trial
4. 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
5. 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)
6. 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
7. Patients in bad general health state according to the investigator's judgment

Primary outcomes:
measure: Change from baseline in limb volume determination at day 84 (water displacement method)
timeFrame: 84 days
Secondary outcomes:
measure: Change from baseline in limb volume determination at day 21 and 42 (water displacement method)
timeFrame: 21 and 42 days
measure: 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
timeFrame: 21, 42 and 84 days
measure: Incidence of adverse events
timeFrame: 84 days
measure: Global assessment of efficacy by the patient at day 84
timeFrame: 84 days
measure: Change from baseline in the calf circumference at day 21, 42 and 84
timeFrame: 21, 42 and 84 days
measure: Global assessment of efficacy by the investigator at day 84
timeFrame: 84 days
measure: Time to improvement in symptoms
timeFrame: 84 days
measure: Vital signs (pulse rate, blood pressure)
timeFrame: 84 days
measure: Number of patients with abnormal Serum Laboratory Parameters
timeFrame: 84 days
measure: Global assessment of tolerability by the patient at day 84
timeFrame: 84 days
measure: Global assessment of tolerability by the investigator at day 84
timeFrame: 84 days
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: 1138.11.49004 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1138.11.49016 Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: 1138.11.49019 Boehringer Ingelheim Investigational Site
city: Bonn
country: Germany
facility: 1138.11.49014 Boehringer Ingelheim Investigational Site
city: Breisach
country: Germany
facility: 1138.11.49023 Boehringer Ingelheim Investigational Site
city: Coburg
country: Germany
facility: 1138.11.49003 Boehringer Ingelheim Investigational Site
city: Dülmen
country: Germany
facility: 1138.11.49024 Boehringer Ingelheim Investigational Site
city: Freiburg
country: Germany
facility: 1138.11.49007 Boehringer Ingelheim Investigational Site
city: Freiburg
country: Germany
facility: 1138.11.49020 Boehringer Ingelheim Investigational Site
city: Greifswald
country: Germany
facility: 1138.11.49009 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 1138.11.49013 Boehringer Ingelheim Investigational Site
city: Lübeck
country: Germany
facility: 1138.11.49010 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1138.11.49011 Boehringer Ingelheim Investigational Site
city: Minden
country: Germany
facility: 1138.11.49012 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1138.11.49005 Boehringer Ingelheim Investigational Site
city: Oberhausen
country: Germany
facility: 1138.11.49022 Boehringer Ingelheim Investigational Site
city: Oberkirch
country: Germany
facility: 1138.11.49002 Boehringer Ingelheim Investigational Site
city: Rottach-Egern
country: Germany
facility: 1138.11.49001 Boehringer Ingelheim Investigational Site
city: Rottweil
country: Germany
facility: 1138.11.49006 Boehringer Ingelheim Investigational Site
city: Tübingen
country: Germany
facility: 1138.11.49018 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Rabe E, Stucker M, Esperester A, Schafer E, Ottillinger B. Efficacy and tolerability of a red-vine-leaf extract in patients suffering from chronic venous insufficiency--results of a double-blind placebo-controlled study. Eur J Vasc Endovasc Surg. 2011 Apr;41(4):540-7. doi: 10.1016/j.ejvs.2010.12.003. Epub 2011 Jan 15.