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

Venous Insufficiency Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00855179
• Other study ID #: 1138.11
• Status: Completed
• Phase: Phase 3
• First received: March 3, 2009
• Last updated: April 30, 2014
• Start date: March 2009

Study information

• Verified date: April 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Venous Insufficiency

Intervention

Drug:
• Red vine leaf extract (AS 195)
Antistax film-coated tablet 360 mg
• Placebo
Placebo tablets identical to those containing Anstistax 360 mg

Locations

Country	Name	City	State
Germany	1138.11.49004 Boehringer Ingelheim Investigational Site	Berlin
Germany	1138.11.49016 Boehringer Ingelheim Investigational Site	Berlin
Germany	1138.11.49019 Boehringer Ingelheim Investigational Site	Bochum
Germany	1138.11.49014 Boehringer Ingelheim Investigational Site	Bonn
Germany	1138.11.49023 Boehringer Ingelheim Investigational Site	Breisach
Germany	1138.11.49003 Boehringer Ingelheim Investigational Site	Coburg
Germany	1138.11.49024 Boehringer Ingelheim Investigational Site	Dülmen
Germany	1138.11.49007 Boehringer Ingelheim Investigational Site	Freiburg
Germany	1138.11.49020 Boehringer Ingelheim Investigational Site	Freiburg
Germany	1138.11.49009 Boehringer Ingelheim Investigational Site	Greifswald
Germany	1138.11.49013 Boehringer Ingelheim Investigational Site	Köln
Germany	1138.11.49010 Boehringer Ingelheim Investigational Site	Lübeck
Germany	1138.11.49011 Boehringer Ingelheim Investigational Site	Mainz
Germany	1138.11.49012 Boehringer Ingelheim Investigational Site	Minden
Germany	1138.11.49005 Boehringer Ingelheim Investigational Site	München
Germany	1138.11.49022 Boehringer Ingelheim Investigational Site	Oberhausen
Germany	1138.11.49002 Boehringer Ingelheim Investigational Site	Oberkirch
Germany	1138.11.49001 Boehringer Ingelheim Investigational Site	Rottach-Egern
Germany	1138.11.49006 Boehringer Ingelheim Investigational Site	Rottweil
Germany	1138.11.49018 Boehringer Ingelheim Investigational Site	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in limb volume determination at day 84 (water displacement method)		84 days	No
Secondary	Change from baseline in limb volume determination at day 21 and 42 (water displacement method)		21 and 42 days	No
Secondary	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	No
Secondary	Incidence of adverse events		84 days	No
Secondary	Global assessment of efficacy by the patient at day 84		84 days	No
Secondary	Change from baseline in the calf circumference at day 21, 42 and 84		21, 42 and 84 days	No
Secondary	Global assessment of efficacy by the investigator at day 84		84 days	No
Secondary	Time to improvement in symptoms		84 days	No
Secondary	Vital signs (pulse rate, blood pressure)		84 days	No
Secondary	Number of patients with abnormal Serum Laboratory Parameters		84 days	No
Secondary	Global assessment of tolerability by the patient at day 84		84 days	No
Secondary	Global assessment of tolerability by the investigator at day 84		84 days	No