Polidocanol Endovenous Microfoam Research Articles

Factors Associated with Recanalization and Reintervention Following Below-knee Polidocanol Endovenous Microfoam Ablation for Great Saphenous and Small Saphenous Veins

Factors Associated with Recanalization and Reintervention Following Below-knee Polidocanol Endovenous Microfoam Ablation for Great Saphenous and Small Saphenous Veins

Factors associated with recanalization and reintervention following below knee polidocanol endovenous microfoam ablation for great saphenous and small saphenous veins

BackgroundPolidocanol endovenous microfoam (PEM) has been used to treat lower extremity venous reflux for almost one decade with specific advantages for below knee (BK) truncal veins where thermal ablation poses a risk of injury to adjacent nerves. The current literature of the BK segment often examines short-term outcomes with modest sample sizes. We aim to identify factors associated with recanalization and reintervention in this subset of patients. MethodsWe performed a retrospective study of a prospectively maintained database of patients from a single institution who underwent 1% PEM ablation for BK great saphenous vein (GSV) and small saphenous vein (SSV) reflux. Patients underwent duplex ultrasound (DU) within 7 days after injection, every 3 to 6 months for 1 year, and every 6 to 12 months thereafter. Patients with symptomatic recanalization underwent reintervention. The 26 patients lost to follow-up without DU after ablation were excluded. The factors associated with recanalization and reintervention were examined by multivariate and nonparametric analyses. ResultsBetween March 2018 and July 2023, 411 patients (166 male, 245 female) with 573 treated limbs (284 right, 289 left) met the study criteria. Of the 573 included limbs, 457 (79.8%) had undergone prior above knee saphenous ablations. A total of 554 BK GSV and 42 SSV ablations were performed. The most recent DU was performed at a mean of 231 ± 329 days. The overall recanalization rate was 10.6% (55 GSVs and 8 SSVs) at a mean follow-up of 104 ± 180 days. Comparing the closed and recanalized veins, we found no significant difference in age (P = .90), treated laterality (P = .14), patient body mass index (P = .59), preprocedural CEAP (clinical-etiology-anatomy-pathophysiology) score (P = .79), recanalization rate in GSVs vs SSVs (P = .06), or administered PEM volume (P = .24). The recanalized veins had significantly larger preprocedural diameters than the veins that remained closed (recanalized, 4.9 mm; closed, 4.3 mm; P = .001). Men had higher incidence of recanalization than women (men, 14.2%; women, 8%; P = .015). Anticoagulation use was associated with recanalization (odds ratio, 1.96; 95% confidence interval, 1.1-3.6; P = .03). Early recanalization at the first DU accounted for 31 failures (49.2%) and had a significantly lower administered PEM volume compared with later recanalization (early, 4 mL; late, 5 mL; P = .025). There were no significant differences between the 33 recanalized patients requiring reintervention (52.4%) and the 30 who did not. Twenty-four reinterventions were performed with PEM, 100% of which remained closed at a median of 160 days (interquartile range, 257 days). ConclusionsPEM is successful for the treatment of BK GSV and SSV reflux with a closure rate of 89% at a mean of 231 days and shows promise as salvage therapy. Most cases of recanalization were noted in the early postprocedure period and were associated with a lower PEM volume. A larger vein diameter, male sex, and anticoagulation use are associated with higher rates of recanalization.

Prospective randomized trial of antithrombotic strategies following great saphenous vein ablation using injectable polidocanol endovenous microfoam (Varithena)

ObjectivePostablation deep vein thrombosis (DVT) represents a potentially serious complication after Varithena polidocanol endovenous microfoam (PEM) ablation. The following primary outcomes were assessed: whether (1) adjunctive apixaban anticoagulation or (2) mechanical deep venous system (DVS) saline flushing could decrease saphenofemoral junction (SFJ) thrombus extension (postablation superficial thrombus extension [PASTE]) and/or DVT compared with compression alone, after great saphenous vein (GSV) PEM ablation. MethodsVarithena 1% PEM ablation patients were randomized to (1) SFJ compression, (2) compression and DVS saline flushing, or (3) compression, DVS saline flushing, and 5 days of postprocedural 5 mg oral apixaban anticoagulation twice daily. Duplex imaging was obtained 7 to 10 days after PEM ablation and PASTE/DVT incidence (primary end point) was compared between groups at this time point. ResultsWe treated 304 limbs in 257 patients with PEM. Overall, 103 limbs received SFJ compression (group C, 33.8%), 101 received compression and deep venous flushing (group D, 32.9%), and 100 received compression, deep flush, and anticoagulation (group A, 33.2%). Mean ultrasound follow-up time was 9.7 days (all patients) with a primary GSV closure rate of 92.4%. SFJ PASTE (II-IV) occurred in 0.9%, 1.0%, and 0% (groups C, D, and A, respectively). DVT occurred in 16.7%, 14.7%, and 1.98% (groups C, D, and A; χ2, P = .002). Patients in group A receiving apixaban anticoagulation had a significant reduction in DVT compared with patients in group C (1.98% vs 16.7%, χ2; P < .001); likewise, patients in group A had a significantly decreased DVT occurrence compared with group D (14.7% vs 1.98%; χ2, P = .00162), whereas patients in groups C and D were not statistically different (16.7% vs 14.7%; χ2, P = .60). Conclusions(1) Neither adjunctive DVS flushing nor anticoagulation decreased clinically relevant SFJ PASTE (II-IV) incidence, which remained similarly low across all groups and ranged between 0% and 1%, regardless of adjunctive DVS flushing or anticoagulation. This rate was significantly lower than prior reports (2.3%-4.1%). (2) DVS flushing had no influence on the rate of DVT. Observed PEM-induced DVT incidence using SFJ compression alone or compression with DVS flushing (16.7% and 14.7%, respectively) was significantly higher than prior reports (2.5%-9.6%). This finding may relate to the greater extent of AK/BK GSV territory treated in the present study. (3) Five days of postprocedural oral apixaban anticoagulation, 5 mg given twice daily, significantly decreased DVT occurrence to 1.98%, compared with nonanticoagulated patients (16.7%). This finding is comparable with the DVT rates reported after endovenous thermal ablation (0.7-1.7%). (4) Postprocedural apixaban anticoagulation may have a significant preventive role in decreasing DVT occurrence after PEM ablation.

Popliteal vein reflux is associated with increased rates of thrombotic complications after small saphenous vein closure procedures

BackgroundVenous insufficiency in the small saphenous vein (SSV) is significantly less common than venous insufficiency in the great saphenous vein; the impact of popliteal vein reflux on SSV closure procedural outcomes has yet to be studied. MethodsA retrospective analysis was performed on 150 SSV closure procedures from 2015 to 2019. Preoperative demographic analysis was performed, after which univariate analyses were performed for postoperative occlusion rates and combined rates of endothermal heat-induced thrombus (EHIT) and endovenous foam-induced thrombus (EFIT). ResultsThe cohort had a mean age of 58 years, and 116 (77%) were female. Fifty-four patients had C2 disease, 76 had C3 disease, 15 had C4 disease, 1 had C5 disease, and 4 had C6 disease. Twenty-three patients (15.3%) were noted to have popliteal vein reflux on their initial venous insufficiency ultrasound study, compared with 127 (84.6%) who did not. Treatment modalities included 84 radiofrequency ablations (56.0%), 37 polidocanol endovenous microfoam (24.6%), and 29 laser ablations (19.3%). When comparing patients with popliteal vein reflux with those without, there was no significant difference in the occlusion rates at their immediate postoperative visit (99.2% vs 95.6%) or at their 6-month postoperative visit (92.1% vs 91.3%). EHIT/EFIT was noted in 4 of the 23 patients with popliteal vein reflux compared with 4 of the 127 patients without popliteal vein reflux (17.3% vs 3.1%; P = .01). All eight instances of EHIT/EFIT were classified as either arteriovenous fistula class I or II EHIT or EFIT, and all were successfully treated without progression to deep vein thrombosis. ConclusionsThe presence of popliteal vein reflux has no impact on postoperative occlusion rates at 6 months; however, it is associated with a significantly increased rate in EHIT and EFIT. Patients should be counseled on this increased risk should they undergo SSV treatment with known popliteal vein reflux.

Treatment of superficial venous insufficiency in a large patient cohort with retrograde administration of ultrasound-guided polidocanol endovenous microfoam versus endovenous laser ablation

Treatment of superficial venous insufficiency in a large patient cohort with retrograde administration of ultrasound-guided polidocanol endovenous microfoam versus endovenous laser ablation

Treatment of superficial venous insufficiency in a large patient cohort with retrograde administration of ultrasound-guided polidocanol endovenous microfoam versus endovenous laser ablation

ObjectiveTo evaluate outcomes among symptomatic patients with superficial chronic venous insufficiency treated with retrograde ultrasound-guided polidocanol endovenous microfoam 1% (PEM) or endovenous laser ablation (EVLA). MethodsThis study is a retrospective chart review from a single vein center between October 2013 and June 2019. Procedures were performed on 1070 patients with Clinical, Etiologic, Anatomic, and Pathophysiologic class 2 to 6 disease and symptomatic superficial venous reflux of the great saphenous vein or anterior accessory saphenous vein. ResultsPEM was used for 550 procedures and patients were followed for 43 ± 13 months; EVLA was used for 520 procedures and patients were followed for 57 ± 18 months. After complete treatment, the elimination of reflux was documented in 93.5% (514/550) and 92.8% (482/520) of the PEM and EVLA procedures, respectively. During the follow-up period, 18% of patients treated with EVLA returned for additional treatment to address residual symptoms in the affected leg. In C6 patients treated with PEM, 69% of ulcers (11/16) healed in less than 1 month, compared with 5% of patients (1/21) treated with EVLA. In C4 patients with lesions, resolution of spontaneous bleeding was 100% in both groups. There were no neurological or cardiac adverse events in the PEM group. Minor complications included asymptomatic deep vein thrombosis (0.5%), one common femoral vein thrombus extension, and superficial venous thrombosis (4%) in the PEM group and asymptomatic deep vein thrombosis (0.8%) and two endovenous heat-induced thromboses in the EVLA group. ConclusionsPEM is comparable in safety and efficacy with EVLA for the treatment of saphenous reflux and associated symptoms. PEM was an effective intervention for most patients with C6 disease. Closure rates in both groups were maintained 36 months after treatment.

Results of polidocanol endovenous microfoam in clinical practice

BackgroundInitial phase III clinical studies with polidocanol endovenous microfoam (PEM) demonstrated its safety and efficacy in the treatment of superficial venous reflux. In those studies, the primary outcome requirement was to assess the improvement in symptoms related to superficial venous disease. The goal of the present study was to evaluate the efficacy of PEM technology in routine clinical practice—specifically, the closure rates after treatment. MethodsWe performed an observational study during which data were prospectively collected from 2 vein centers using an electronic database. Patients with CEAP (clinical, etiologic, anatomic, pathophysiologic) class ≥2 and symptomatic superficial axial reflux (great saphenous vein, anterior accessory saphenous vein, and small saphenous vein) were included and followed up prospectively. PEM was used to treat the saphenous vein and varicosities. The CEAP classification was used to classify chronic venous disease, and the venous clinical severity score (VCSS) was applied to measure the disease severity. Pain and discomfort were assessed using a visual analog scale, and the residual veins were assessed by physical examination. ResultsPEM was used to treat superficial reflux in 60 patients. The CEAP classification was C2 for 32 patients, C3 for 14, C4 for 10, and C5 for 4 patients. The average pretreatment VCSS was 7.3. The saphenous vein diameter was 6.5 mm, and the average length was 31 cm. The average volume of PEM used to treat the saphenous veins was 9.3 mL. The closure rate at 3 and 6 months was 93% (54 of 58) and 93% (51 of 55), respectively. The VCSS had improved from 7.3 to 1.4. Complications included 1 case of deep vein thrombosis (1.7%), 5 patients (8.3%) with thrombophlebitis, and 4 patients (6.6%) with skin pigmentation. ConclusionsPEM is safe and effective for the treatment of saphenous reflux and varicosities. The early closure rates using PEM were maintained at 6 months and are comparable to the results reported with nonthermal, nontumescent technologies and thermal tumescent technologies.

Use of Polidocanol Endovenous Microfoam to Improve Hemodynamics and Symptomology in Patients with Challenging Clinical Presentations: A Case Series

Chronic venous insufficiency (CVI) is a widely prevalent condition. Saphenous venous reflux is the most common underlying pathology that leads to CVI. Endovenous thermal ablations (ETA) are the current gold standard. However, some patients present with some unique challenges making ETA less ideal. Nonthermal nontumescent therapies could be considered as alternative therapy in these patients. We performed a retrospective review of treatment effects with United States Food and Drug Administration-approved polidocanol endovenous microfoam (PEM; Varithena® 1%) on venous symptomology in 10 (n=10) C3-C6 patients with CVI and concomitant complex disease/pathology that limited the use of ETA. The pathology included risk of bruising or bleeding, severe lipodermatosclerosis, hidradenitis suppurativa, chronic fibrosis of the vein from prior superficial thrombosis, risk for nerve injury, and failed prior ETA. Before treatment, all patients underwent a venous incompetence study by duplex ultrasound (DUS). Preprocedure pain, symptoms, and Venous Clinical Severity Scores (VCSSs) were recorded. Clinical assessments and DUS were performed 4 days, 6 weeks, 6 months, and 1 year after treatment. DUS demonstrated reflux in the great saphenous vein (GSV), anterior accessory GSV, and/or the small saphenous vein. Pain scores and VCSS were reduced 4days and 6weeks after treatment. These lower scores were maintained for up to 1year after treatment. PEM use in C3-C6 patients resulted in successful improvement in VCSS, CVI symptoms, and wound healing among patients in whom ETA was not considered to be the optimal therapy.

Relationship between patient-reported symptoms, limitations in daily activities, and psychological impact in varicose veins.

The objective of this study was to evaluate the relationship between patient-reported symptoms, functional limitations, and psychological impact of varicose veins (VVs) vs pathophysiologic mechanism, incorporating demographic and behavioral factors. We conducted a pooled analysis from two clinical studies (Efficacy and Safety Study of Polidocanol Injectable Foam for the Treatment of Saphenofemoral Junction Incompetence [VANISH-1] and Polidocanol Endovenous Microfoam Versus Vehicle for the Treatment of Saphenofemoral Junction Incompetence [VANISH-2]) in patients with VVs (superficial venous reflux only). Health outcomes were classified on the basis of the Wilson-Cleary conceptual framework continuum linking clinical and anatomic factors (Clinical, Etiology, Anatomy, and Pathophysiology [CEAP] clinical class and great saphenous vein [GSV] diameter, respectively) to patient-reported outcomes: Varicose Vein Symptoms Questionnaire (VVSymQ) score; modified Venous Insufficiency Epidemiologic and Economic Study on Quality of Life/Symptoms (m-VEINES-QOL/Sym) limitations in daily activities (functional limitations hereafter) score; and m-VEINES-QOL/Sym psychological impact score. Association of clinical and anatomic categories with each of the patient-reported outcomes was assessed using analysis of variance for statistical significance and standardized mean differences for clinical meaningfulness. Hierarchical regression modeling was applied to evaluate the direct association of the VVSymQ symptom score with the m-VEINES-QOL/Sym functional limitations score and the indirect association with the m-VEINES-QOL/Sym psychological impact score, adjusting for clinical, behavioral, and demographic factors. Among 516 patients, approximately three-fourths were women (mean age, 49 years), approximately 70% were overweight or obese, 42% were C2 and 32% were C3, and 88% reported never or only intermittently wearing compression stockings. VVSymQ (symptom) scores did not vary by GSV diameter but were significantly worse for those with severe disease stage, especially C5 or C6. Among m-VEINES-QOL/Sym work-related function items, 47% of patients reported difficulty at work and 31% reported cutting down at work. On nonwork function items, standing for prolonged periods was most affected; 53% were limited a little and 22% were limited a lot. Concern about appearance and choice of clothing predominated among psychological impact items, with 74% and 65%, respectively, affected all or most of the time. The m-VEINES-QOL/Sym functional limitation and psychological impact scores varied by neither GSV diameter nor CEAP C class, but they varied directly with VVSymQ (symptom) score quartiles. Multivariable regression analysis revealed that VVSymQ symptom scores continued to be associated with m-VEINES-QOL/Sym psychological impact scores, even after adjustment for m-VEINES-QOL/Sym functional limitation scores. Substantial patient-reported functional limitation and psychological impact of VVs were observed. Limitations on work, standing for prolonged periods, concern about appearance, and clothing choice were most affected. Patient-reported VVSymQ (symptom) score, an objective patient-reported measure of symptom severity in VVs, was the key predictor of patient-reported m-VEINES-QOL/Sym functional limitations. Symptoms and functional limitations led to greater psychological impact. Physicians should routinely ascertain symptoms and functional limitations to enhance quality of care and to document medical necessity.

Novel developments in foam sclerotherapy: Focus on Varithena® (polidocanol endovenous microfoam) in the management of varicose veins.

Scope Varithena® is a recently approved commercially available drug/delivery unit that produces foam using 1% polidocanol for the management of varicose veins. The purpose of this review is to examine the benefits of foam sclerotherapy, features of the ideal foam sclerosant and the strengths and limitations of Varithena® in the context of current foam sclerotherapy practices. Method Electronic databases including PubMed, Medline (Ovid) SP as well as trial registries and product information sheets were searched using the keywords, 'Varithena', 'Varisolve', 'polidocanol endovenous microfoam', 'polidocanol' and/or 'foam sclerotherapy/sclerosant'. Articles published prior to 20 September 2016 were identified. Results Foam sclerosants have effectively replaced liquid agents due to their physiochemical properties resulting in better clinical outcomes. Medical practitioners commonly prepare sclerosant foam at the bedside by agitating liquid sclerosant with a gas such as room air, using techniques as described by Tessari or the double syringe method. Such physician-compounded foams are highly operator dependent producing inconsistent foams of different gas/liquid compositions, bubble size, foam behaviour and varied safety profiles. Varithena® overcomes the variability and inconsistencies of physician-compounded foam. However, Varithena® has limited applications due to its fixed sclerosant type and concentration, cost and lack of worldwide availability. Clinical trials of Varithena® have demonstrated efficacy and safety outcomes equivalent or better than physician-compounded foam but only in comparison to placebo alone. Conclusion Varithena® is a promising step towards the creation of an ideal sclerosant foam. Further assessment in independent randomised controlled clinical trials is required to establish the advantages of Varithena® over and above the current best practice physician-compounded foam.

Corrigendum

Corrigendum to Improvement in patient-reported outcomes of varicose veins following treatment with polidocanol endovenous microfoam. Phlebology. DOI: 10.1177/0268355516678512. First Published January 23, 2017 The following errors were corrected on the initial version of this paper: All instances of VVSymQ® have been replaced with VVSymQ™. More details has been added to the conflicts in interests and funding statements, which now read.

Improvement in patient-reported outcomes of varicose veins following treatment with polidocanol endovenous microfoam.

Objective To evaluate the relationship between patient-reported symptoms and functional and psychological impact of varicose veins following treatment with polidocanol endovenous microfoam (PEM) 1%. Methods Data were pooled from two randomized trials on VV treatment. Wilson-Cleary health outcomes path model was applied to evaluate impact of VVSymQ™ symptom score improvement on modified VEINES-QOL/Sym functional and psychological scores. Change scores were evaluated for (i) PEM 1% versus placebo groups and (ii) quartiles of symptom improvement. Cumulative distribution function curves were generated to compare percentage of patients with various levels of functional and psychological improvement including clinically meaningful improvement across two treatment groups. Multivariable regression models of change scores and clinically meaningful changes were estimated. Results In 221 patients (109 PEM 1%; 112 placebo), PEM 1% was associated with median improvements of 2.5 points and 4.0 points on the m-VEINES-QOL/Sym functional limitations and m-VEINES-QOL/Sym psychological limitations scores, compared to 0 and 1.0 point improvements, respectively, for placebo. Cumulative distribution function curves revealed that 20-30% more patients in PEM 1% group achieved clinically meaningful functional and psychological improvement versus placebo group. Conclusions Patients with above-average symptom improvement had better functional and psychological improvement. PEM 1% treatment had higher odds of clinically meaningful functional and psychological improvement.

A multicenter, randomized, placebo-controlled study to evaluate the efficacy and safety of Varithena® (polidocanol endovenous microfoam 1%) for symptomatic, visible varicose veins with saphenofemoral junction incompetence.

ObjectivesA randomized, placebo-controlled, multicenter study was conducted to evaluate the safety and efficacy of polidocanol endovenous microfoam (1%, Varithena® [polidocanol injectable foam], BTG International Ltd.).MethodsPatients (n = 77) with symptomatic, visible varicose veins were randomized to treatment with either Varithena 1% or placebo.ResultsVarithena provided greater mean changes from Baseline in patient-reported assessments of symptoms (e.g., heaviness, achiness, swelling, throbbing, itching [HASTI®] score 30.7 points vs 16.7 points, p = 0.0009, primary endpoint; and modified Venous Insufficiency Epidemiological and Economic Study-Quality-of-Life/Symptoms [m-VEINES-QOL/Sym; p < 0.001]), physician-assessed VCSS, and physician- and patient-assessed appearance compared with placebo.The HASTI score correlated highly with the modified-VEINES-QOL/Sym and Chronic Venous Insufficiency Questionnaire-2 scores (r = 0.7 to > 0.9, p ≤ 0.001). Adverse events included contusion, incision-site hematoma, and limb discomfort. Venous thrombus adverse events were reported as mild and generally resolved without sequelae.ConclusionsVarithena provided significantly greater symptom relief and improvement in leg appearance compared with placebo. Adverse events were generally mild and transient. (www.clinicaltrials.gov [NCT00758420]).

A multicenter, randomized, placebo-controlled trial of endovenous thermal ablation with or without polidocanol endovenous microfoam treatment in patients with great saphenous vein incompetence and visible varicosities.

Objectives *Varithena 017 Investigator Group: Michael Vasquez, MD, Venous Institute of Buffalo, Amherst, NY; Antonios Gasparis, MD, Stony Brook University Medical Center, Stony Brook, NY; Kathleen Gibson, MD, Lake Washington Vascular, Bellevue, WA; James Theodore King, MD, Vein Clinics of America, Oakbrook Terrace, IL; Nick Morrison, MD, Morrison Vein Institute, Scottsdale, AZ; Girish Munavalli, MD, Dermatology, Laser & Vein Specialists of the Carolinas, Charlotte, NC; Eulogio J. Sanchez, MD, Batey Cardiovascular Center, Bradenton, FL. Varithena® is a trademark of Provensis Ltd, a BTG International group company.To determine the efficacy and safety of polidocanol endovenous microfoam (PEM 0.5%, 1.0%) and placebo each administered with endovenous thermal ablation.MethodsA multicenter, randomized, placebo-controlled, blinded study was conducted in patients with great saphenous vein incompetence and symptomatic and visible superficial venous disease. Co-primary endpoints were physician-assessed and patient-assessed appearance change from Baseline to Week 8.ResultsA total of 117 patients received treatment (38 placebo, 39 PEM 0.5%, 40 PEM 1%). Physician-rated vein appearance at Week 8 was significantly better with PEM (p = 0.001 vs. placebo); patient-assessed appearance trended similarly. Polidocanol endovenous microfoam provided improvements in clinically meaningful change in patient-assessed and physician-assessed appearance (p < 0.05), need for additional treatment (p < 0.05), saphenofemoral junction reflux elimination, symptoms, and QOL. In PEM recipients, the most frequent adverse event was superficial thrombophlebitis (35.4%)ConclusionsEndovenous thermal ablation + PEM significantly improved physician-assessed appearance at Week 8, increased the proportion of patients with a clinically meaningful change in appearance, and reduced need for additional treatment. www.clinicaltrials.gov (NCT01197833)

The role of clinically-relevant parameters on the cohesiveness of sclerosing foams in a biomimetic vein model.

We have recently reported on the development of a biomimetic vein model to measure the performance of sclerosing foams. In this study we employed the model to compare the commercially-available Varithena® (polidocanol injectable foam) 1 % varicose vein treatment (referred to as polidocanol endovenous microfoam, or PEM) with physician compounded foams (PCFs) made using different foam generation methods (Double Syringe System and Tessari methods) and different foam formulations [liquid to gas ratios of 1:3 or 1:7; gas mixtures composed of 100 % CO2, various CO2:O2 mixtures and room air (RA)]. PCFs produced using the DSS method had longer dwell times (DTs) (range 0.54–2.21 s/cm in the 4 mm diameter vein model) than those of the corresponding PCFs produced by the Tessari technique (range 0.29–0.94 s/cm). PEM had the longest DT indicating the best cohesive stability of any of the foams produced (2.92 s/cm). Other biomimetic model variables investigated included effect of vessel size, delayed injection and rate of plug formation (injection speed). When comparing the 4 and 10 mm vessel diameters, the DTs seen in the 10 mm vessel were higher than those observed for the 4 mm vessel, as the vein angle had been reduced to 5° to allow for foam plug formation. PCF foam performance was in the order RA > CO2:O2 (35:65) ≅ CO2:O2 (65:35) > CO2; PEM had a longer DT than all PCFs (22.10 s/cm) except that for RA made by DSS which was similar but more variable. The effect of delayed injection was also investigated and the DT for PEM remained the longest of all foams with the lowest percentage deviation with respect to the mean values, indicating a consistent foam performance. When considering rate of plug formation, PEM consistently produced the longest DTs and this was possible even at low plug expansion rates (mean 29.5 mm/s, minimum 20.9 mm/s). The developed vein model has therefore demonstrated that PEM consistently displays higher foam stability and cohesiveness when compared to PCFs, over a range of clinically-relevant operational variables.Electronic supplementary materialThe online version of this article (doi:10.1007/s10856-015-5587-z) contains supplementary material, which is available to authorized users.

Treatment of Truncal Incompetence and Varicose Veins with a Single Administration of a New Polidocanol Endovenous Microfoam Preparation Improves Symptoms and Appearance

This multicenter, parallel group study was designed to determine if a single administration of ≤15mL of pharmaceutical-grade polidocanol endovenous microfoam (PEM, now approved in the United States as Varithena [polidocanol injectable foam], BTG International Ltd.) could alleviate symptoms and improve appearance of varicose veins in a typical population of patients with moderate to very severe symptoms of superficial venous incompetence and visible varicosities of the great saphenous vein (GSV) system. The primary endpoint was patient-reported venous symptom improvement measured by change from baseline to Week 8 in 7-day average VVSymQ score. Co-secondary endpoints measured improvement in appearance of visible varicose veins from baseline to Week 8, as measured by the Independent Photography Review-Visible Varicose Veins (IPR-V(3)) and Patient Self-assessment of Visible Varicose Veins (PA-V(3)) scores. Patients were randomized to five groups: PEM 0.125% (control), 0.5%, 1%, 2%, or placebo. Adverse events (AEs) were recorded at each study visit. Tertiary endpoints measured duplex ultrasound response, changes in venous clinical severity score, and the modified Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms. At Week 8, VVSymQ scores for the pooled PEM group (0.5%+1%+2%; p<.0001) and individual dose concentrations (p<.001) were significantly superior to placebo. Mean changes from baseline to Week 8 in IPR-V3 and PA-V(3) scores were significantly greater for pooled PEM than for placebo (p<.0001). Most AEs were mild and resolved without sequelae. No pulmonary emboli were reported. This study demonstrated that a single administration of up to 15mL of PEM is a safe, effective, and convenient treatment for the symptoms of superficial venous incompetence and the appearance of visible varicosities of the GSV system. Doses of 0.5%, 1%, and 2% PEM appear to have an acceptable risk-benefit ratio.

Durability of treatment effect with polidocanol endovenous microfoam on varicose vein symptoms and appearance (VANISH-2).

The objectives of this study were to assess the durability of response to treatment with polidocanol endovenous microfoam (Varithena; Provensis Ltd, a BTG International group company) and to assess the long-term safety of the study patients. This report presents efficacy and safety data from the day after visit 5/week 8 (the primary end point of the study) through the 1-year study visit. As the approved dose concentration is 1%, this analysis focuses on those patients who were randomized to polidocanol endovenous microfoam 1% at study visit 2. Because the objective of the 1-year analysis was to assess the durability of response to treatment with polidocanol endovenous microfoam 1%, the 1-year efficacy analyses based on the efficacy population included all patients who were randomized and received at least one treatment with polidocanol endovenous microfoam 1%. Efficacy end points in the Polidocanol Endovenous Microfoam Versus Vehicle for the Treatment of Saphenofemoral Junction Incompetence (VANISH-2) trial were evaluated at 1 year (n = 221; 96% of those completed the primary end-point measurement at week 8) and included the following: Varicose Vein Symptoms Questionnaire (VVSymQ, Provensis Ltd) score, an assessment of symptoms by patients using electronic daily diaries; Independent Photography Review: Visible Varicose Veins (IPR-V(3)) and Patient Self-assessment of Visible Varicose Veins (PA-V(3)) scores, the assessment of appearance by an Independent Physician Review panel and by patient self-assessment, respectively; duplex ultrasound response (physiologic response to treatment); Venous Clinical Severity Score (disease severity); and Venous Insufficiency Epidemiological and Economic Study on Quality of Life (VEINES-QOL) score (quality of life). Of the 230 patients who completed visit 5/week 8, 56 received polidocanol endovenous microfoam 1% at visit 2/week 0 and were subsequently assessed for efficacy at visit 5/week 8 and visit 10/1 year (one patient of the 57 who completed visit 5/week 8 received a nonpolidocanol endovenous microfoam intervention and was not included in the assessment). At 1 year after the first study treatment, patients treated with polidocanol endovenous microfoam demonstrated consistent, durable, and clinically meaningful improvements in symptoms, as measured by reductions in mean VVSymQ score; appearance, as measured by IPR-V(3) (clinician assessment) and PA-V(3) (patient self-assessment) scores; disease severity, as measured by the Venous Clinical Severity Score; and quality of life, as measured by the VEINES-QOL score. At 1 year, there were no new venous thrombus adverse events (VTAEs) and no clinically important sequelae in patients who had a VTAE in the study. In addition, there were no serious adverse events that were determined by the investigator to be related to the study drug. No new safety signals were identified. In patients who previously had a VTAE, none had a recurrence of thrombus or evidence of post-thrombotic syndrome at 1 year. Treatment with polidocanol endovenous microfoam 1% led to durable, clinically meaningful, and ongoing improvements at 1 year in varicose vein symptoms and appearance. Serious adverse events were those expected during long-term follow-up of the population of patients studied and were unrelated to treatment.

Abstract No. 522 - Evaluating the expected budget impact and cost-effectiveness of interventional therapies used in the treatment of chronic venous disease

Purpose Varicose veins (VV) and resulting sequelae contribute to morbidity assoc w/chronic vein disorders (CVD), impacting QOL and resulting in ~ $1B/yr. Total cost minimization and budget impact evaluation assessed 8-wk diff between Varithena ® (polidocanol endovenous microfoam [PEM]) vs alternate tx for VV in US from a 3rd-party payer perspective. Materials and Methods Tx options incl PEM, EVLA, RFA, surgery, and multi-modality tx, defined >1 tx on same day. Total cost components incl (wholesale) drug acquisition costs , pmt for professional (CMS physician fee schedule) and institutional (Hospital Outpatient Prospective Pmt System) services related to initial intervention, weighted for each modality, plus expected costs of addl interventions, weighted by corresponding rate of addl interventions, within 8-wk time frame. Evidence on rate of addl interventions for PEM came from 2 pooled, phase 3 studies, and for other modalities from US retrospective claims analysis of pts w/VV. Budget impact was modeled for hypothetical 1M member plan w/evidence-based assumptions: 76% adults, 6% chronic venous insufficiency prevalence, and 31% rate of interventional tx among pts w/dx VV, and derived in terms of total and per-member-per-month (PMPM) expenditure change given 5% initial PEM market share. Results PEM was expected to cost $2,165 (incl $615 (28%) for addl tx) compared to $2,374 (14% for addl tx) for surgery, $2,106 (32% for addl tx) for RFA, $1,827 (38% for addl tx) for EVLA, and $2,844 (26% for addl tx) for multi-modality tx. Budget impact for 1M member hypothetical health plan was $87k or $0.01 PMPM. Conclusion PEM is expected to have slightly lower addl tx rates than and cost ~ same as RFA and EVLA (performed alone) but be less costly than surgery and multi-modality tx (≥2 interventions on same day) for VV tx. Adding PEM to the formulary for a health plan is ~ budget neutral. Exp 8-wk Costs, Tx Options Comparator Initial tx costs Addtl tx rate Expected addtl tx cost Total expected costs PEM $1550 39.7% $615 $2165 EVLA $1130 52.4% $697 $1827 RFA $1430 40.0% $676 $2106 Surgery $2049 17.9% $325 $2374 Multi-modality tx $2107 34.9% $737 $2844

An Integrated Subgroup Analysis of the Effect of Treatment with Polidocanol Endovenous Microfoam on VVSymQ Score in Patients with Varicose Veins.

An Integrated Subgroup Analysis of the Effect of Treatment with Polidocanol Endovenous Microfoam on VVSymQ Score in Patients with Varicose Veins.

The Durability of Polidocanol Endovenous Microfoam Treatment Effect on Varicose Vein Symptoms and Appearance in Patients with Saphenofemoral Junction Incompetence: One-Year Results from the VANISH-2 Study.

The Durability of Polidocanol Endovenous Microfoam Treatment Effect on Varicose Vein Symptoms and Appearance in Patients with Saphenofemoral Junction Incompetence: One-Year Results from the VANISH-2 Study.