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Study of Antiinflammatory Effects of Detralex (Daflon)

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ClinicalTrials.gov Identifier: NCT01654016
Recruitment Status : Completed
First Posted : July 31, 2012
Last Update Posted : November 1, 2019
Sponsor:
Collaborator:
Servier
Information provided by (Responsible Party):
Marko Ajduk, MD PhD, University Hospital Dubrava

Tracking Information
First Submitted Date  ICMJE July 24, 2012
First Posted Date  ICMJE July 31, 2012
Last Update Posted Date November 1, 2019
Study Start Date  ICMJE August 2012
Actual Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2012)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2012)
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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Antiinflammatory Effects of Detralex (Daflon)
Official Title  ICMJE Study of Antiinflammatory Effects of Detralex (Daflon) in Patients With Chronic Venous Disease
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Chronic Venous Insufficiency
Intervention  ICMJE Drug: Detralex
Detralex 500 mg twice daily for three month prior to surgery
Other Name: Daflon
Study Arms  ICMJE
  • Active Comparator: Detralex
    Detralex 500 mg twice daily for three month prior to surgery
    Intervention: Drug: Detralex
  • No Intervention: Not taking Detralex
    Not taking Detralex for three months prior to surgery
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 27, 2012)
84
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2019
Actual Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Croatia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01654016
Other Study ID Numbers  ICMJE Detra-001-Ajd
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Marko Ajduk, MD PhD, University Hospital Dubrava
Study Sponsor  ICMJE University Hospital Dubrava
Collaborators  ICMJE Servier
Investigators  ICMJE
Principal Investigator: Marko Ajduk, PhD University Hospital Dubrava
PRS Account University Hospital Dubrava
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP