Chronic Venous InsufficiencyPhase 4NCT01654016
Study of Antiinflammatory Effects of Detralex (Daflon)
A Phase 4 study testing Detralex in people with Chronic Venous Insufficiency, run by University Hospital Dubrava at 1 site in Croatia.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Venous Insufficiency
- What is being tested?
- Detralex
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 1 siteCroatia
- Study dates
- Aug 2012to Sep 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic venous disease (CEAP 2 and 3) and saphenofemoral insufficiency
Who cannot join
- 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:
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study of Antiinflammatory Effects of Detralex (Daflon) in Patients With Chronic Venous Disease
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).
Read the 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).
- Conditions
- Chronic Venous Insufficiency
- Being tested
- Detralex
- Keywords
- varicose veins, inflammation
- Medical subject headings
- Varicose Veins, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DetralexDrug
Also called Daflon
Detralex 500 mg twice daily for three month prior to surgery
| Study group | Role | What they receive |
|---|---|---|
| Detralex | Active comparator | Detralex 500 mg twice daily for three month prior to surgery Receives: Drug: Detralex |
| Not taking Detralex | No intervention | Not taking Detralex for three months prior to surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 14 months
Secondary outcomes (1)
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
Measured: 14 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2012 (estimated)
- Study startAug 2012
- Primary completionMay 2019
- Study completionSep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Chronic Venous InsufficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Dubrava
- Sponsor type
- University, hospital or other
- Collaborators
- Servier
- Responsible party
- Principal investigator, Marko Ajduk, MD PhD, University Hospital Dubrava
- Investigators
- Marko Ajduk, PhD, Principal investigator, University Hospital Dubrava
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01654016
- Sponsor's protocol ID
- Detra-001-Ajd
- Status last verified
- Oct 2019
- First submitted
- 24 Jul 2012
- Last updated
- 1 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Eberhardt RT, Raffetto JD. Chronic venous insufficiency. Circulation. 2005 May 10;111(18):2398-409. doi: 10.1161/01.CIR.0000164199.72440.08. No abstract available.
PubMed 15883226Nicolaides AN. From symptoms to leg edema: efficacy of Daflon 500 mg. Angiology. 2003 Jul-Aug;54 Suppl 1:S33-44. doi: 10.1177/0003319703054001S05.
PubMed 12934755Sezer 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.
PubMed 21768702Perrin 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.
PubMed 21126890Bergan JJ. Chronic venous insufficiency and the therapeutic effects of Daflon 500 mg. Angiology. 2005 Sep-Oct;56 Suppl 1:S21-4. doi: 10.1177/00033197050560i104.
PubMed 16193222Martinez-Zapata MJ, Vernooij RW, Simancas-Racines D, Uriona Tuma SM, Stein AT, Moreno Carriles RMM, Vargas E, Bonfill Cosp X. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 2020 Nov 3;11(11):CD003229. doi: 10.1002/14651858.CD003229.pub4.
PubMed 33141449
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Antiinflammatory Effects of Detralex (Daflon) in Patients With Chronic Venous Disease
- ClinicalTrials.gov ID
- NCT01654016
- Acronym / sponsor ID
- Detra-001-Ajd
- Conditions
- Chronic Venous Insufficiency
- Keywords
- varicose veins, inflammation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- University Hospital DubravaUniversity, hospital or other
- Collaborators
- Servier
- Study start
- Aug 2012
- Primary completion
- May 2019 (actual)
- Study completion
- Sep 2019 (actual)
- First posted
- 31 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Detralex | Active comparator | Drug: DetralexDetralex 500 mg twice daily for three month prior to surgery |
| Not taking Detralex | No intervention | –Not taking Detralex for three months prior to surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Chronic venous disease (CEAP 2 and 3) and saphenofemoral insufficiency
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DetralexAlso: DaflonDetralex 500 mg twice daily for three month prior to surgery | Drug | Detralex |
Primary outcome
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
1 secondary outcome
Clinical effects of Detralex (Daflon)
Time frame: 14 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2019.
- Background: PubMed 15883226Eberhardt RT, Raffetto JD. Chronic venous insufficiency. Circulation. 2005 May 10;111(18):2398-409. doi: 10.1161/01.CIR.0000164199.72440.08. No abstract available.
- Background: PubMed 12934755Nicolaides AN. From symptoms to leg edema: efficacy of Daflon 500 mg. Angiology. 2003 Jul-Aug;54 Suppl 1:S33-44. doi: 10.1177/0003319703054001S05.
- Background: PubMed 21768702Sezer 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.
- Background: PubMed 21126890Perrin 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.
- Background: PubMed 16193222Bergan JJ. Chronic venous insufficiency and the therapeutic effects of Daflon 500 mg. Angiology. 2005 Sep-Oct;56 Suppl 1:S21-4. doi: 10.1177/00033197050560i104.
- Derived from this study: PubMed 33141449Martinez-Zapata MJ, Vernooij RW, Simancas-Racines D, Uriona Tuma SM, Stein AT, Moreno Carriles RMM, Vargas E, Bonfill Cosp X. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 2020 Nov 3;11(11):CD003229. doi: 10.1002/14651858.CD003229.pub4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marko Ajduk, PhD principal investigator
University Hospital Dubrava
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Detralex in people with Chronic Venous Insufficiency, run by University Hospital Dubrava at 1 site in Croatia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Antiinflammatory Effects of Detralex (Daflon) (time frame: 14 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01654016, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2019.