Venous Insufficiency of LegNCT02936271
Efficacy of Vasculera in Prevention on Post-op Pain and Edema Following Lower Extremity Venous Treatment in the Outpatient Setting
A study testing Vasculera in people with Venous Insufficiency of Leg and Venous Reflux, run by Corewell Health West at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the effectiveness of Vasculera in reducing post procedural pain, bruising and edema in the post procedure period for patients diagnosed with C2-C5 disease requiring an intervention(s). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Venous Insufficiency of Leg, Venous Reflux, Varicose Veins
- What is being tested?
- Vasculera
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2016to 1 Apr 2017
- Phase
- Interventional
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients 18 years of age or older with C2-C5 disease undergoing radiofrequency ablation; foam and/or sclerotherapy
- Women of childbearing age must be using birth control to be candidates for study participation
Who cannot join
- Pregnant or nursing women
- Patients that are 85 years of age or older
- Patients who are unable to provide consent
- Prisoners or vulnerable population, including non-English speaking patients
- C1 Disease
- Patient on Chlorzoxazone, Diclofenac, Metronidazole
Show all 9Show fewer
- Use of recreational drugs including alcohol in excess of 1 unit daily (for purposes of this study, a unit of alcohol is defined as 6 oz of wine, 12 oz of beer or 2 oz of hard spirits)
- Participation in another clinical trial within 7 half-lives of the prior study agent prior to the screening visit
- More than three planned surgical intervention procedures
Trial locations and contacts
1 site in 1 country.
United States1 site
Spectrum Health Hospitals
Grand Rapids, Michigan, 49503
About this study
Official title: Efficacy of Vasculera in Prevention on Post-op Pain and Edema Following Lower Extremity Venous Treatment in the Outpatient Setting.
The purpose of this study is to evaluate the effectiveness of Vasculera in reducing post procedural pain, bruising and edema in the post procedure period for patients diagnosed with C2-C5 disease requiring an intervention(s).
The hypothesis is that Vasculera will reduce post procedural pain, bruising and edema for patients requiring an intervention.
Read more
This will be a randomized, double-blind, placebo-controlled study. Vasculera is a specially formulated prescription medical food product for the clinical dietary management of the metabolic processes of chronic venous insufficiency. Vasculera has limited side effects, please see the product insert.
A total of 110 patients will be enrolled into this study. Patients will be randomized to receive Vasculera (Study Product) or placebo. Study Product or placebo will be prescribed as one (1) tablet twice a day.
Read the detailed description
Lower extremity venous disease is thought to affect 50 percent of woman and 40 percent of men at some point in their lifetime. Many of these patients seek venous treatment and undergo surgical procedures in the outpatient setting. Patient undergoing surgical intervention for treatment of venous reflux disease often experience discomfort, edema and discoloration in the areas of treatment. These symptoms may affect them for weeks to months after the procedure.
Radiofrequency ablation (RFA) of greater saphenous, small saphenous or accessory saphenous vein follow by sclerotherapy of remaining tributary veins 1-2 weeks later is a common minimally invasive treatment. Both the RFA and the ultrasound guided sclerotherapy cause an inflammatory response which can make the post-operative period more difficult for patients then the procedure itself.
Vasculara has been shown to reduce inflammation, improve vascular tone and decrease tissue acidosis. It has also been shown to be effective in the treatment of post phlebitic syndrome and may reduce thrombotic complication. Recent animal data has demonstrated decreased postsclerotherapy inflammation in rabbits. In anecdotal reports providers have had good result with prescribing this medication to patients to be take a week or two prior to the procedure and in the post-op period, however, evidence for this practice is lacking. Vasculara is a generally safe product with very limited side effects and thus could be applied to a large patient population if clear benefit were documented.
Vasculera is a prescription medical food product composed of the flavonoid, diosmin and a proprietary systemic blood alkalinizing agent, Alka4-complex. Diosmin has been used successfully in Europe for more than 35 years in the treatment of chronic venous insufficiency and its complications. There is a large body of published literature regarding the molecular activity, clinical efficacy and safety of diosmin as well as its effects on the microvasculature where it has been shown to reduce inflammation, improve structural integrity, improve capillary flow and reduce capillary leakage of serum proteins and red blood cells. It decreases bradykinin-induced microvascular leakage and may act favorably to inhibit leukocyte activation, trapping, and migration. Clinically, edema is reduced, ulcer healing is accelerated, and leukocyte trapping diminished.
A similar study with similar design to this study from a Russian group demonstrated the "feasibility of using the drug Detralex, a brand of diosmin marketed in Europe, as an agent for nonspecific pharmacological protection in endovascular treatment of varicose disease." In 2007 the DEFANS trial, also from Russia concluded, micronized diosmin in pre- and postoperative period after phlebectomy helps to attenuate pain syndrome, to decrease postoperative hematomas and accelerate their resorption, to increase exercise tolerance in early postoperative period. Studies performed within the United States with modern surgical procedures are lacking.
- Being tested
- Vasculera, Placebo
- Keywords
- Radiofrequency Ablation, Sclerotherapy, Vasculera
- Medical subject headings
- Varicose Veins
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VasculeraOther
Also called Diosmiplex, Prescription medical food product
Vasculera is a specially formulated prescription medical food product. This study compares Vasculera to placebo at reducing post procedural pain, bruising and edema for patients requiring an intervention for lower extremity venous disease.
Patient will be randomized to receive Active Vasculera or Vasculera Placebo. The study product will be taken for two weeks prior to the patient's planned procedure and continued for four weeks after their procedure. If multiple procedures are required the patient will be instructed to use the product throughout treatment.
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Active Vasculera (diosmiplex) | Active comparator | Active Vasculera will be prescribed as one (1) tablet (630 mg) twice a day. Receives: Other: Vasculera |
| Vasculera Placebo | Placebo comparator | Vasculera Placebo will be prescribed as one (1) tablet twice a day. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post-procedure Bruising
Physician and nurse examination
Measured: 2 weeks pre-procedure to 6 weeks post-procedure
Post-procedure Bleeding
Physician and nurse examination
Measured: 2 weeks pre-procedure to 6 weeks post-procedure
Post-procedure Pain
Pain scale
Measured: 2 weeks pre-procedure to 6 weeks post-procedure
Post-procedure Edema
Physician and nurse examination
Measured: 2 weeks pre-procedure to 6 weeks post-procedure
Secondary outcomes (2)
Adverse Events
Adverse events per package insert.
Measured: 2 weeks pre-procedure to 6 weeks post-procedure
Serious Adverse Events
Deep Vein Thrombosis (DVT) Pulmonary Embolism (PE) and Infection.
Measured: 2 weeks pre-procedure to 6 weeks post-procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2016 (estimated)
- Study startOct 2016
- Primary completion1 Apr 2017
- Study completion1 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Venous Insufficiency of LegStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Corewell Health West
- Sponsor type
- University, hospital or other
- Collaborators
- Primus Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Jennifer J. Watson, MD, Principal investigator, Corewell Health West
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02936271
- Sponsor's protocol ID
- 2016-137
- Status last verified
- Nov 2022
- First submitted
- 3 Oct 2016
- Last updated
- 23 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Brand FN, Dannenberg AL, Abbott RD, Kannel WB. The epidemiology of varicose veins: the Framingham Study. Am J Prev Med. 1988 Mar-Apr;4(2):96-101.
PubMed 3395496Callam MJ. Epidemiology of varicose veins. Br J Surg. 1994 Feb;81(2):167-73. doi: 10.1002/bjs.1800810204.
PubMed 8156326Zahariev T, Anastassov V, Girov K, Goranova E, Grozdinski L, Kniajev V, Stankev M. Prevalence of primary chronic venous disease: the Bulgarian experience. Int Angiol. 2009 Aug;28(4):303-10.
PubMed 19648874Bergan 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 16193222Tsimoyiannis EC, Floras G, Antoniou N, Papanikolaou N, Siakas P, Tassis A. Low-molecular-weight heparins and Daflon for prevention of postoperative thromboembolism. World J Surg. 1996 Oct;20(8):968-71; discussion 972. doi: 10.1007/s002689900145.
PubMed 8798349de Souza Md, Cyrino FZ, Mayall MR, Virgini-Magalhaes CE, Sicuro FL, de Carvalho JJ, Verbeuren TJ, Bouskela E. Beneficial effects of the micronized purified flavonoid fraction (MPFF, Daflon(R) 500 mg) on microvascular damage elicited by sclerotherapy. Phlebology. 2016 Feb;31(1):50-6. doi: 10.1177/0268355514564414. Epub 2014 Dec 15.
PubMed 25514922Lyseng-Williamson KA, Perry CM. Micronised purified flavonoid fraction: a review of its use in chronic venous insufficiency, venous ulcers and haemorrhoids. Drugs. 2003;63(1):71-100. doi: 10.2165/00003495-200363010-00005.
PubMed 12487623Ramelet AA. Clinical benefits of Daflon 500 mg in the most severe stages of chronic venous insufficiency. Angiology. 2001 Aug;52 Suppl 1:S49-56. doi: 10.1177/0003319701052001S07.
PubMed 11510597Shoab SS, Scurr JH, Coleridge-Smith PD. Plasma VEGF as a marker of therapy in patients with chronic venous disease treated with oral micronised flavonoid fraction - a pilot study. Eur J Vasc Endovasc Surg. 1999 Oct;18(4):334-8. doi: 10.1053/ejvs.1999.0890.
PubMed 10550269Bogachev VIu, Golovanova OV, Kuzhetsov AN, Shekoian AO. [On advisability of perioperative phleboprotection in endovascular treatment of lower in varicose disease: first initial results of the decision study]. Angiol Sosud Khir. 2012;18(2):90-5. Russian.
PubMed 22929677International Task Force. The management of chronic venous disorders of the leg: an evidence-based report of an international task force. Epidemiology. Phlebology. 1999;14(suppl 1):23-34.
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Vasculera in Prevention on Post-op Pain and Edema Following Lower Extremity Venous Treatment in the Outpatient Setting.
- ClinicalTrials.gov ID
- NCT02936271
- Acronym / sponsor ID
- 2016-137
- Keywords
- Radiofrequency Ablation, Sclerotherapy, Vasculera
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Corewell Health WestUniversity, hospital or other
- Collaborators
- Primus Pharmaceuticals
- Study start
- Oct 2016
- Primary completion
- 1 Apr 2017 (actual)
- Study completion
- 1 Apr 2017 (actual)
- First posted
- 18 Oct 2016 (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.
The purpose of this study is to evaluate the effectiveness of Vasculera in reducing post procedural pain, bruising and edema in the post procedure period for patients diagnosed with C2-C5 disease requiring an intervention(s).
The hypothesis is that Vasculera will reduce post procedural pain, bruising and edema for patients requiring an intervention.
This will be a randomized, double-blind, placebo-controlled study. Vasculera is a specially formulated prescription medical food product for the clinical dietary management of the metabolic processes of chronic venous insufficiency. Vasculera has limited side effects, please see the product insert.
A total of 110 patients will be enrolled into this study. Patients will be randomized to receive Vasculera (Study Product) or placebo. Study Product or placebo will be prescribed as one (1) tablet twice a day.
Detailed description
Lower extremity venous disease is thought to affect 50 percent of woman and 40 percent of men at some point in their lifetime. Many of these patients seek venous treatment and undergo surgical procedures in the outpatient setting. Patient undergoing surgical intervention for treatment of venous reflux disease often experience discomfort, edema and discoloration in the areas of treatment. These symptoms may affect them for weeks to months after the procedure.
Radiofrequency ablation (RFA) of greater saphenous, small saphenous or accessory saphenous vein follow by sclerotherapy of remaining tributary veins 1-2 weeks later is a common minimally invasive treatment. Both the RFA and the ultrasound guided sclerotherapy cause an inflammatory response which can make the post-operative period more difficult for patients then the procedure itself.
Vasculara has been shown to reduce inflammation, improve vascular tone and decrease tissue acidosis. It has also been shown to be effective in the treatment of post phlebitic syndrome and may reduce thrombotic complication. Recent animal data has demonstrated decreased postsclerotherapy inflammation in rabbits. In anecdotal reports providers have had good result with prescribing this medication to patients to be take a week or two prior to the procedure and in the post-op period, however, evidence for this practice is lacking. Vasculara is a generally safe product with very limited side effects and thus could be applied to a large patient population if clear benefit were documented.
Vasculera is a prescription medical food product composed of the flavonoid, diosmin and a proprietary systemic blood alkalinizing agent, Alka4-complex. Diosmin has been used successfully in Europe for more than 35 years in the treatment of chronic venous insufficiency and its complications. There is a large body of published literature regarding the molecular activity, clinical efficacy and safety of diosmin as well as its effects on the microvasculature where it has been shown to reduce inflammation, improve structural integrity, improve capillary flow and reduce capillary leakage of serum proteins and red blood cells. It decreases bradykinin-induced microvascular leakage and may act favorably to inhibit leukocyte activation, trapping, and migration. Clinically, edema is reduced, ulcer healing is accelerated, and leukocyte trapping diminished.
A similar study with similar design to this study from a Russian group demonstrated the "feasibility of using the drug Detralex, a brand of diosmin marketed in Europe, as an agent for nonspecific pharmacological protection in endovascular treatment of varicose disease." In 2007 the DEFANS trial, also from Russia concluded, micronized diosmin in pre- and postoperative period after phlebectomy helps to attenuate pain syndrome, to decrease postoperative hematomas and accelerate their resorption, to increase exercise tolerance in early postoperative period. Studies performed within the United States with modern surgical procedures are lacking.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Vasculera (diosmiplex) | Active comparator | Other: VasculeraActive Vasculera will be prescribed as one (1) tablet (630 mg) twice a day. |
| Vasculera Placebo | Placebo comparator | Other: PlaceboVasculera Placebo will be prescribed as one (1) tablet twice a day. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients 18 years of age or older with C2-C5 disease undergoing radiofrequency ablation; foam and/or sclerotherapy
- Women of childbearing age must be using birth control to be candidates for study participation
Key exclusion criteria (9 listed)
- Pregnant or nursing women
- Patients that are 85 years of age or older
- Patients who are unable to provide consent
- Prisoners or vulnerable population, including non-English speaking patients
- C1 Disease
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 |
|---|---|---|
| VasculeraAlso: Diosmiplex, Prescription medical food productVasculera is a specially formulated prescription medical food product. This study compares Vasculera to placebo at reducing post procedural pain, bruising and edema for patients requiring an intervention for lower extremity venous disease. Patient will be randomized to receive Active Vasculera or Vasculera Placebo. The study product will be taken for two weeks prior to the patient's planned procedure and continued for four weeks after their procedure. If multiple procedures are required the patient will be instructed to use the product throughout treatment. | Other | Active Vasculera (diosmiplex) |
| Placebo | Other | Vasculera Placebo |
Primary outcome
Post-procedure Bruising
Time frame: 2 weeks pre-procedure to 6 weeks post-procedure
Physician and nurse examination
Post-procedure Bleeding
Time frame: 2 weeks pre-procedure to 6 weeks post-procedure
Physician and nurse examination
Post-procedure Pain
Time frame: 2 weeks pre-procedure to 6 weeks post-procedure
Pain scale
Post-procedure Edema
Time frame: 2 weeks pre-procedure to 6 weeks post-procedure
Physician and nurse examination
2 secondary outcomes
Adverse Events
Time frame: 2 weeks pre-procedure to 6 weeks post-procedure
Serious Adverse Events
Time frame: 2 weeks pre-procedure to 6 weeks post-procedure
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2022.
- Background: PubMed 3395496Brand FN, Dannenberg AL, Abbott RD, Kannel WB. The epidemiology of varicose veins: the Framingham Study. Am J Prev Med. 1988 Mar-Apr;4(2):96-101.
- Background: PubMed 8156326Callam MJ. Epidemiology of varicose veins. Br J Surg. 1994 Feb;81(2):167-73. doi: 10.1002/bjs.1800810204.
- Background: PubMed 19648874Zahariev T, Anastassov V, Girov K, Goranova E, Grozdinski L, Kniajev V, Stankev M. Prevalence of primary chronic venous disease: the Bulgarian experience. Int Angiol. 2009 Aug;28(4):303-10.
- 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.
- Background: PubMed 8798349Tsimoyiannis EC, Floras G, Antoniou N, Papanikolaou N, Siakas P, Tassis A. Low-molecular-weight heparins and Daflon for prevention of postoperative thromboembolism. World J Surg. 1996 Oct;20(8):968-71; discussion 972. doi: 10.1007/s002689900145.
- Background: PubMed 25514922de Souza Md, Cyrino FZ, Mayall MR, Virgini-Magalhaes CE, Sicuro FL, de Carvalho JJ, Verbeuren TJ, Bouskela E. Beneficial effects of the micronized purified flavonoid fraction (MPFF, Daflon(R) 500 mg) on microvascular damage elicited by sclerotherapy. Phlebology. 2016 Feb;31(1):50-6. doi: 10.1177/0268355514564414. Epub 2014 Dec 15.
- Background: PubMed 12487623Lyseng-Williamson KA, Perry CM. Micronised purified flavonoid fraction: a review of its use in chronic venous insufficiency, venous ulcers and haemorrhoids. Drugs. 2003;63(1):71-100. doi: 10.2165/00003495-200363010-00005.
- Background: PubMed 11510597Ramelet AA. Clinical benefits of Daflon 500 mg in the most severe stages of chronic venous insufficiency. Angiology. 2001 Aug;52 Suppl 1:S49-56. doi: 10.1177/0003319701052001S07.
- Background: PubMed 10550269Shoab SS, Scurr JH, Coleridge-Smith PD. Plasma VEGF as a marker of therapy in patients with chronic venous disease treated with oral micronised flavonoid fraction - a pilot study. Eur J Vasc Endovasc Surg. 1999 Oct;18(4):334-8. doi: 10.1053/ejvs.1999.0890.
- Background: PubMed 22929677Bogachev VIu, Golovanova OV, Kuzhetsov AN, Shekoian AO. [On advisability of perioperative phleboprotection in endovascular treatment of lower in varicose disease: first initial results of the decision study]. Angiol Sosud Khir. 2012;18(2):90-5. Russian.
- BackgroundInternational Task Force. The management of chronic venous disorders of the leg: an evidence-based report of an international task force. Epidemiology. Phlebology. 1999;14(suppl 1):23-34.
- Product websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Jennifer J. Watson, MD principal investigator
Corewell Health West
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vasculera in people with Venous Insufficiency of Leg and Venous Reflux, run by Corewell Health West at 1 site in United States.
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 2 inclusion and 9 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: withdrawn, as of the sponsor's last update on 23 Nov 2022. 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 United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Post-procedure Bruising (time frame: 2 weeks pre-procedure to 6 weeks post-procedure). The study lists 4 primary outcomes in all. 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 NCT02936271, which also lists 11 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 23 Nov 2022.