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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Venous Insufficiency of Leg, Venous Reflux, Varicose Veins, Lower Extremity Edema Chronic

Intervention / Treatment
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* Other: Vasculera
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Vasculera (diosmiplex)<br>Active Vasculera will be prescribed as one (1) tablet (630 mg) twice a day. | Other: Vasculera<br>* 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.<br>* Other names: Prescription medical food product;|
| Placebo Comparator: Vasculera Placebo<br>Vasculera Placebo will be prescribed as one (1) tablet twice a day. | Other: Placebo<br> <br> |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiofrequency Ablation, Sclerotherapy, Vasculera