Study of Antiinflammatory Effects of Detralex (Daflon)

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Servier
Information provided by (Responsible Party):
Marko Ajduk, MD PhD, University Hospital Dubrava
ClinicalTrials.gov Identifier:
NCT01654016
First received: July 24, 2012
Last updated: August 20, 2012
Last verified: August 2012
  Purpose

Aim of the study:

To investigate if there is a differences in expression of inflammatory markers in venous wall and blood among patients treated with Detralex and those not treated with Detralex (control group).


Condition Intervention Phase
Chronic Venous Insufficiency
Drug: Detralex
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Study of Antiinflammatory Effects of Detralex (Daflon) in Patients With Chronic Venous Disease

Further study details as provided by University Hospital Dubrava:

Primary Outcome Measures:
  • Antiinflammatory Effects of Detralex (Daflon) [ Time Frame: 14 months ] [ Designated as safety issue: No ]

    The following markers of inflammation will be analyzed:

    Blood (biochemical analysis): soluble ICAM-1, soluble VCAM-1, E-selectin, L selectin PAI-1, TIMP-1, Angiopoietin-1, Angiopoietin-2 and Tie-2.

    Vein wall ([immuno]histological and biochemical analysis) : CD 45 (leukocytes), S100 (C-fibers), MMP3, MMP9, SMC (smooth muscle cells). Presence (or not) of microthrombi in the vein lumen



Secondary Outcome Measures:
  • Clinical effects of Detralex (Daflon) [ Time Frame: 14 months ] [ Designated as safety issue: Yes ]

    Subjective perception of pain, leg heaviness, cramping and itching will be assessed using visual analogue scale (VAS) graded from 0 to 10. Leg edema will be assessed by measuring the leg circumference. Data will be recorded as follow:

    1. three months before the surgery
    2. one day before the surgery
    3. one week after the surgery
    4. one month after bthe surgery
    5. three months after the surgery


Estimated Enrollment: 84
Study Start Date: August 2012
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Detralex
Detralex 500 mg twice daily for three month prior to surgery
Drug: Detralex
Detralex 500 mg twice daily for three month prior to surgery
Other Name: Daflon
No Intervention: Not taking Detralex
Not taking Detralex for three months prior to surgery

Detailed Description:

Chronic venous disease (CVD) represents one of the most common vascular disorder. It's different clinical manifestations (most often seen as varicose veins) can be observed in up to 40% of adult female population and in about 30% of adult males.

Different mechanical and biological factors play role in the process of deterioration of venous wall tone and consequent vein valve disfunction that eventually lead to increase venous pressure . Evidence suggest that inflammation has a central place in this process even from the early stage of CVD.

Usual symptoms of venous insufficiency are pain, leg heaviness, night cramping, itching, and are often accompanied with leg edema. The extent of clinical manifestation may not correlate with patients' symptoms. Treatment of varicose veins encompasses vein surgery (stripping, phlebectomy, radiofrequency and laser ablation), sclerotherapy and compression therapy. Detralex (in some countries registered as Daflon) is an oral flavonoid that consists of 90% micronized diosmin and 10% flavonoids expressed as hesperidin. Several studies showed some beneficial effects of Detralex in alleviating symptoms in patients with CVD. It may be used in conjunction with surgery, sclerotherapy, or compression therapy or it may be the only therapy when other therapeutical modalities are not indicated or not feasable.

Animal studies showed antiinflammatory effects of Daflon in way that Daflon acts favorably on microcirculatory complications by normalizing the synthesis of prostaglandins and free radicals. It decreases bradykinin-induced microvascular leakage and inhibits leukocyte activation, trapping, and migration.

However, by searching the available literature (MEDLINE) we found no study that investigated what are the antiinflammatory effects of flavonoids in humans.

The aim of this study is to investigate if there is a differences in expression of inflammatory markers in venous wall and blood between patients treated with Detralex and those not treated with Detralex (control group).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Chronic venous disease (CEAP 2 and 3) and saphenofemoral insufficiency

Exclusion Criteria:

  • Previous deep venous thrombosis
  • Previous or acute thrombophlebitis of the GSV (confirmed by duplex findings - morphologic changes of the GSV above the knee)
  • Immunological disorders
  • Diabetes type I or II,
  • Severe inflammatory disease: such as Behcet, lupus, Horton and other arteritis, polyarthritis, spondylarthritis or sclerodermia
  • Recent (less than 3 months) or scheduled non-authorized non-pharmacological treatments:
  • Sclerotherapy,
  • Surgical treatment of varicose veins (crossectomy, phlebectomy),
  • Endovenous treatment (endovenous laser, radiofrequency),
  • Non-authorized pharmacological treatment in the last 3 months and during the study:
  • Anti-inflammatory agents (except acetylsalicylic acid at dose 350 mg daily),
  • Systemic corticosteroids or immunosuppressives,
  • Venoactive drugs including open label MPFF,
  • Pentoxifylline
  • Patients already (at the time of randomization) taking Detralex for symptoms linked to chronic venous disease
  • Arterial insufficiency (absent pedal pulses or ABI < 0.9)
  • Any important clinical or laboratory abnormalities
  • Pregnancy, breastfeeding or wish of becoming pregnant during the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01654016

Locations
Croatia
University Hospital Dubrava
Zagreb, Croatia, 10000
Sponsors and Collaborators
University Hospital Dubrava
Servier
Investigators
Principal Investigator: Marko Ajduk, PhD University Hospital Dubrava
  More Information

Publications:
Responsible Party: Marko Ajduk, MD PhD, Principal Investigator, University Hospital Dubrava
ClinicalTrials.gov Identifier: NCT01654016     History of Changes
Other Study ID Numbers: Detra-001-Ajd
Study First Received: July 24, 2012
Last Updated: August 20, 2012
Health Authority: Croatia: Agency for Medicinal Product and Medical Devices

Keywords provided by University Hospital Dubrava:
varicose veins
inflammation

Additional relevant MeSH terms:
Venous Insufficiency
Vascular Diseases
Cardiovascular Diseases
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014