Study of Antiinflammatory Effects of Detralex (Daflon)

Phase 4

Completed

• Conditions: Chronic Venous Insufficiency
• Interventions: Drug: Detralex

• Registration Number: NCT01654016
• Lead Sponsor: 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).

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).

Study Timeline

• Study First Submitted: 2012-07-24
• Study First Submitted QC: 2012-07-27
• Study First Posted: 2012-07-31
• Study Start: 2012-08
• Primary Completion: 2019-05
• Study Completion: 2019-09
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-31
• Last Update Posted: 2019-11-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 84

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Detralex	Detralex	Detralex 500 mg twice daily for three month prior to surgery

Primary Outcome Measures

Name	Time	Method
Antiinflammatory Effects of Detralex (Daflon)	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

Name	Time	Method
Clinical effects of Detralex (Daflon)	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

Trial Locations

Locations (1)

University Hospital Dubrava; 🇭🇷 Zagreb, Croatia