Efficacy of Vasculera in Prevention on Post-op Pain and Edema Following Lower Extremity Venous Treatment in the Outpatient Setting

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.

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.

Study Overview

• Status: Withdrawn
• Conditions: Varicose Veins; Venous Insufficiency of Leg; Venous Reflux; Lower Extremity Edema Chronic
• Intervention / Treatment: Other: Placebo; Other: Vasculera

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 Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Vasculera (diosmiplex); Active Vasculera will be prescribed as one (1) tablet (630 mg) twice a day.	Other: Vasculera; 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.; Other Names: Diosmiplex; Prescription medical food product
Placebo Comparator: Vasculera Placebo; Vasculera Placebo will be prescribed as one (1) tablet twice a day.	Other: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-procedure Bruising	Physician and nurse examination	2 weeks pre-procedure to 6 weeks post-procedure
Post-procedure Bleeding	Physician and nurse examination	2 weeks pre-procedure to 6 weeks post-procedure
Post-procedure Pain	Pain scale	2 weeks pre-procedure to 6 weeks post-procedure
Post-procedure Edema	Physician and nurse examination	2 weeks pre-procedure to 6 weeks post-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Adverse events per package insert.	2 weeks pre-procedure to 6 weeks post-procedure
Serious Adverse Events	Deep Vein Thrombosis (DVT) Pulmonary Embolism (PE) and Infection.	2 weeks pre-procedure to 6 weeks post-procedure

Collaborators and Investigators

• Sponsor: Spectrum Health Hospitals
• Collaborators: Primus Pharmaceuticals
• Investigators: Principal Investigator: Jennifer J. Watson, MD, Spectrum Health Hospitals

Publications and helpful links

General 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.
• Callam MJ. Epidemiology of varicose veins. Br J Surg. 1994 Feb;81(2):167-73. doi: 10.1002/bjs.1800810204.
• Zahariev 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.
• Bergan 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.
• Tsimoyiannis 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.
• de 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.
• Lyseng-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.
• Ramelet 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.
• Shoab 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.
• Bogachev 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.
• International 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.

Helpful Links

• Product website

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: October 3, 2016
• First Submitted That Met QC Criteria: October 14, 2016
• First Posted (Estimate): October 18, 2016

Study Record Updates

• Last Update Posted (Actual): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 22, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Sclerotherapy; Radiofrequency Ablation; Vasculera
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Edema; Venous Insufficiency; Varicose Veins
• Other Study ID Numbers: 2016-137

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No