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

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.

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