Study of Antiinflammatory Effects of Detralex (Daflon)

Chronic Venous Insufficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01654016
• Other study ID #: Detra-001-Ajd
• Status: Completed
• Phase: Phase 4
• Start date: August 2012
• Est. completion date: September 2019

Study information

• Verified date: October 2019
• Source: University Hospital Dubrava
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: September 2019
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Venous Insufficiency
• Venous Insufficiency

Intervention

Drug:
• Detralex
Detralex 500 mg twice daily for three month prior to surgery

Locations

Country	Name	City	State
Croatia	University Hospital Dubrava	Zagreb

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Dubrava	Servier

Country where clinical trial is conducted

Croatia, 

References & Publications (5)

Bergan JJ. Chronic venous insufficiency and the therapeutic effects of Daflon 500 mg. Angiology. 2005 Sep-Oct;56 Suppl 1:S21-4. Review. — View Citation

Eberhardt RT, Raffetto JD. Chronic venous insufficiency. Circulation. 2005 May 10;111(18):2398-409. Review. — View Citation

Nicolaides AN. From symptoms to leg edema: efficacy of Daflon 500 mg. Angiology. 2003 Jul-Aug;54 Suppl 1:S33-44. Review. — View Citation

Perrin M, Ramelet AA. Pharmacological treatment of primary chronic venous disease: rationale, results and unanswered questions. Eur J Vasc Endovasc Surg. 2011 Jan;41(1):117-25. doi: 10.1016/j.ejvs.2010.09.025. Epub 2010 Dec 3. Review. — View Citation

Sezer A, Usta U, Kocak Z, Yagci MA. The effect of a flavonoid fractions diosmin + hesperidin on radiation-induced acute proctitis in a rat model. J Cancer Res Ther. 2011 Apr-Jun;7(2):152-6. doi: 10.4103/0973-1482.82927. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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