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Study of Antiinflammatory Effects of Detralex (Daflon)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01654016
Recruitment Status : Completed
First Posted : July 31, 2012
Last Update Posted : November 1, 2019
Information provided by (Responsible Party):
Marko Ajduk, MD PhD, University Hospital Dubrava

Brief Summary:

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 or disease Intervention/treatment Phase
Chronic Venous Insufficiency Drug: Detralex Phase 4

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Study of Antiinflammatory Effects of Detralex (Daflon) in Patients With Chronic Venous Disease
Study Start Date : August 2012
Actual Primary Completion Date : May 2019
Actual Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Antiinflammatory Effects of Detralex (Daflon) [ Time Frame: 14 months ]

    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 :
  1. Clinical effects of Detralex (Daflon) [ Time Frame: 14 months ]

    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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01654016

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University Hospital Dubrava
Zagreb, Croatia, 10000
Sponsors and Collaborators
University Hospital Dubrava
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Principal Investigator: Marko Ajduk, PhD University Hospital Dubrava
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Marko Ajduk, MD PhD, Principal Investigator, University Hospital Dubrava Identifier: NCT01654016    
Other Study ID Numbers: Detra-001-Ajd
First Posted: July 31, 2012    Key Record Dates
Last Update Posted: November 1, 2019
Last Verified: October 2019
Keywords provided by Marko Ajduk, MD PhD, University Hospital Dubrava:
varicose veins
Additional relevant MeSH terms:
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Venous Insufficiency
Vascular Diseases
Cardiovascular Diseases