Study of Antiinflammatory Effects of Detralex (Daflon)

Study Overview
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Brief Summary
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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).

Detailed Description
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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).

Official Title
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Study of Antiinflammatory Effects of Detralex (Daflon) in Patients With Chronic Venous Disease

Conditions
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Chronic Venous Insufficiency

Intervention / Treatment
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* Drug: Detralex


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Detralex<br>Detralex 500 mg twice daily for three month prior to surgery | Drug: Detralex<br>* Detralex 500 mg twice daily for three month prior to surgery<br>* Other names: Daflon;|
| No Intervention: Not taking Detralex<br>Not taking Detralex for three months prior to surgery | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antiinflammatory Effects of Detralex (Daflon) | 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 | 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical effects of Detralex (Daflon) | 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: three months before the surgery one day before the surgery one week after the surgery one month after bthe surgery three months after the surgery | 14 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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varicose veins, inflammation