Abstract
Objective
Chronic venous hypertension, triggered by venous reflux and/or obstruction, leads to skin changes and venous leg ulcers (VLUs). Compression therapy is the standard of care, but many wounds remain unhealed. The objectives of this study were to observe the effects of endovenous chemical ablation with commercially available 1% polidocanol injectable microfoam on VLU healing and recurrence rates.
Methods
The VIEW VLU study was a multicenter, open-label, phase IV registry of patients with active VLUs resulting from venous insufficiency of the great saphenous vein and/or anterior accessory saphenous vein systems who underwent ablation with 1% polidocanol microfoam. Primary outcomes included wound healing rate (change in wound perimeter), wound closure at 12 weeks after treatment, and time to wound closure. Secondary outcomes included VLU recurrence, numeric pain score at the ulcer location, EuroQol five-dimension five-level questionnaire quality-of-life index, and the Venous Clinical Severity Score. Patients were followed for 12 months.
Results
We enrolled 76 patients (80 ulcers) from 14 sites across the United States and Canada (mean age 63.6 ± 13.7 years, 39.5% female, mean body mass index 36.3). Of the enrollees, 96.3% presented with great saphenous vein incompetence. The mean baseline wound perimeter was 117.2 ± 107.4 mm and 26.3% of wounds (21/80) were circumferential. The mean ulcer age was 34.8 ± 51.8 weeks at first presentation and the mean compression therapy duration was 26.4 ± 35.9 weeks. The median wound perimeter decreased by 16.3% from baseline in the first 2 weeks after the procedure and by 27.0% at 12 weeks. By 12 weeks, 53.8% of wounds (43/80) were healed. The median time to ulcer closure by Kaplan-Meier analysis was 89 days (95% confidence interval, 62.0-117.0). In a Kaplan-Meier analysis of initially healed wounds, 88.9% (95% confidence interval, 76.9-94.8) remained closed at 12 weeks after closure. The mean numeric pain scores (ulcer site) improved by 41.0% and 64.1% at 12 weeks and 12 months after the procedure, respectively. The health-related quality-of-life index (scale of 0-1) improved from 0.65 ± 0.27 at baseline to 0.72 ± 0.28 at 12 weeks and 0.73 ± 0.30 at 12 months. By 12 weeks after treatment, the mean target leg Venous Clinical Severity Score had significantly decreased by 5.8 points, and by 12 months it had decreased by 10.0 points.
Conclusions
Treatment with 1% polidocanol microfoam was associated with promising wound healing rates and low recurrence rates for VLUs, despite a challenging patient population with recalcitrant ulcers, a large percentage of which were circumferential, in patients with high body mass indexes.
Keywords: Polidocanol, Sclerotherapy, Venous reflux, Venous leg ulcer, Chemical ablation
Article Highlights.
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Type of Research: Multicenter, prospective registry
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Key Findings: We included 76 patients with venous leg ulcers who underwent endovenous ablation with 1% polidocanol microfoam. By 12 weeks, 53.8% of ulcers were healed and 75% healed by 1 year.
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Take Home Message: In a challenging population, Varithena treatment was associated with enhanced ulcer healing.
Between 1.5 and 3.0 in 1000 people have active venous leg ulcers (VLUs), with prevalence increasing with age to approximately 20 in 1000 people aged more than 80 years.1 VLUs cause significant morbidity and pose a substantial financial burden to the health care system.2 The pathophysiology of VLUs is multifactorial,3 but it is accepted that underlying chronic venous hypertension owing to reflux and/or obstruction plays a significant role.4,5 This venous hypertension in the larger veins is transmitted to the skin's microcirculation, contributing to chronic changes in the soft tissue and skin.6
Treatment guidelines support compression therapy as the primary therapeutic modality for decreasing reflux and healing VLUs.7,8 However, many wounds remain unhealed with high recurrence rates. Recently, the Early Venous Reflux Ablation (EVRA) trial demonstrated that early endovenous ablation of superficial venous reflux reduces the time to VLU healing, increases ulcer-free time, and is likely to be cost effective.9,10 In EVRA, foam sclerotherapy was the most common endovenous treatment method used (211/450 patients had it as the only ablation type9) and outnumbered those treated with thermal and nonthermal catheter-based ablation combined. Sclerotherapy may target the terminal reflux or eliminate venous hypertension of reservoir vessels in the small venules at or near the ulcer bed. Small studies have also shown foam sclerotherapy to improve ulcer healing rates11, 12, 13 and to decrease recurrence rates14 over compression therapy alone.
The VIEW-VLU study aimed to observe the treatment effect of endovenous chemical ablation with 1% polidocanol injectable microfoam that has been approved by the US Food and Drug Administration (Varithena, Boston Scientific, Marlborough, MA) on the rate of VLU healing, rate of ulcer recurrence, and effect on ulcer site pain and quality of life.
Methods
Study design
The VIEW-VLU study was a multicenter, open-label, 12-month phase IV registry of patients with active VLUs resulting from venous insufficiency of the great saphenous vein (GSV) and/or anterior accessory saphenous vein (AASV) systems who were treated with 1% polidocanol injectable microfoam that has been approved by the US Food and Drug Administration. The study protocol was approved by the institutional review board or research ethics board applicable to each study site, and patients were required to provide informed consent before participation in any trial-related evaluations. The study is registered with ClinicalTrials.gov, identifier: NCT03257254.
Patients
Complete inclusion and exclusion criteria are shown in the Supplementary Table (online only). In brief, patients aged 18 years or older whose venous symptoms were classified as Clinical, Etiological, Anatomical, and Pathophysiological (ie, CEAP)15 class C6 with VLU duration of 3 months or more resulting from GSV and/or AASV incompetence (reflux time >500 ms on duplex ultrasound examination) and for whom the investigator had selected 1% polidocanol injectable microfoam to treat the saphenous incompetence and varicosities were eligible. Ulcers were required to be able to be visualized in a single plane to allow the patient to capture the entire wound in one digital photograph; for circumferential wounds, the patient must have been able to capture the entire wound with multiple digital photographs. Patients were excluded if they had any serious concomitant disease that would confound wound healing (including malignant changes of the wound), underwent concomitant thermal ablation or thermal ablation of the index leg within 6 weeks before 1% polidocanol microfoam treatment, had significant arterial disease or ankle-brachial index of 0.8 or less, or if, in the opinion of the investigator, the wound would close within 12 weeks without additional treatment.
Treatment
Polidocanol (1%) injectable microfoam was used to treat reflux in the saphenous trunk, the varicosities, and the varicose tributaries in the proximity of the ulcer bed. Administration procedures were per standard of care, prescribing information, and instructions for use. Per these instructions, microfoam was administered above and/or below the knee via a single cannula into the lumen of the target incompetent trunk veins or by direct injection into varicosities. Up to 15 mL of 1% polidocanol microfoam could be administered in the index session, with each injection not exceeding 5 mL. Postprocedure care, including compression dressings, was used in accordance with the instructions for use (ie, “apply compression bandaging and stockings and have the patient walk for at least 10 minutes, while being monitored; maintain compression for 2 weeks after treatment”) and investigator's standard of care. The type of compression procedures were not assessed. Additional endovenous polidocanol microfoam treatments were administered at the investigator's discretion and according to the prescribing information, no sooner than 5 days after the previous treatment. Patients were treated at a local wound care center for routine wound care until wound closure.
Evaluations and outcome definitions
Follow-up visits were scheduled (±1 week) for 1 week, 12 weeks, and 12 months after treatment. Duplex ultrasound examinations were scheduled per the site's standard of care. All patients received a computer tablet to collect digital wound images (eg, during dressing changes at the wound care center) and numeric pain score data on a weekly basis from week 2 through wound closure (or 12 weeks, whichever was later) and requested again through telephone follow-up at 6 months. Patients reported pain at the ulcer location on a scale of 0 (no pain) to 10 (worst pain). Investigators collected digital photographs of the wound at baseline and week 12. Investigators evaluated VLU recurrence at 3 months after wound closure and 6 months after treatment via phone call and/or patient-captured photographs, and at the 12-month (post-treatment) follow-up visit.
The primary outcome, the wound healing rate, was evaluated as the rate of epithelial migration (millimeters per week) measured by wound perimeter on photographs submitted for independent central imaging analysis. Additional primary outcomes included the wound closure rate at 12 weeks (±1 week) after treatment and time from initial treatment to wound closure. Closure was defined as complete epithelialization. Recurrence was defined as reopened wounds at the same location.
The EuroQol Five Dimension Five-level Questionnaire (EQ-5D-5L) quality-of-life assessment16 and the Venous Clinical Severity Score (VCSS) of the treated leg were collected at baseline, 12 weeks, and 12 months after treatment. Higher EQ-5D-5L health-related quality-of-life index values indicate greater health utility, with 1 representing full health.16
Digital wound photographs and central imaging assessment
A computer tablet-based central wound imaging application (Tissue Analytics, Baltimore, MD) was used to capture digital photographs of the wounds. The computer application measured and quantified the wound perimeter to minimize subjectivity in wound measurement.17 At the week 1 follow-up visit, patients received training in the use of the wound image application on their tablet. A green sticker was placed on the skin in the same plane as the wound to serve as a reference marker to enable wound size calibration by the computer application. For ulcers that spanned more than a single plane or were circumferential, multiple digital photographs were acquired in different planes and pieced together electronically by the computer application. All wound photographs were submitted via the tablet application for independent evaluation of wound color and size. In addition, a wound expert independent of the central imaging application reviewed each photograph to ensure the wound perimeter was appropriately mapped and to verify wound closure.
Statistical analyses
Wound perimeter measurements were used to assess the rate of epithelial migration (ie, change in wound size), wound closure rates, and time to wound closure. Recurrence was assessed among patients with wounds initially healed at least 3 months before the patient’s exit from the study (ie, complete follow-up, patient discontinuation, or study close). The proportion of these patients’ wounds remaining healed was estimated with Kaplan-Meier analysis and 95% confidence intervals (CIs). Censoring occurred on the date of last study contact if there was no recurrence. Log-log transformation methodology was used to calculate 95% CI.18
For the VCSS, the difference in score from baseline at each visit was calculated; the mean and 95% CI are reported. The mean pain scores and the percent change for mean scores compared with baseline is reported. Summary statistics and 95% CI for the EQ-5D-5L health-related quality-of-life index are reported. Statistical analyses were performed with SAS (SAS Institute Inc., Cary, NC), version 9.4 or higher.
Results
Patients
From September 2017 to February 2020, 76 patients (80 ulcers) from 14 investigation sites across the United States and Canada were enrolled in the study. Seventy-one of 76 patients (93.4%) completed follow-up through at least 12 weeks and the median duration in the study was 11.8 months. Study enrollment was ended in February 2020 and study follow-up was terminated in September 2020. Thus, five patients did not complete 12-month follow-up owing to study discontinuation. Another 16 patients withdrew or were lost to follow-up (Supplementary Fig, online only).
Supplementary Fig (online only).
Patient flow diagram.
Patient demographics, clinical characteristics, and wound characteristics are shown in Table I. The mean body mass index (BMI) was 36.3 ± 10.2 with 67.1% of patients having a BMI of 30 or higher. The percentages of wounds represented in the registry with incompetent GSV, AASV, major perforators, or small saphenous vein (SSV) are shown in Table I. Four patients (5.3%) had bilateral ulcers. The mean age of the ulcers at presentation was more than 8 months (Table I). Of the 80 ulcers, 26.3% were circumferential. Among ulcers with evaluable wound perimeter measurements (n = 65), the mean baseline perimeter was 117.2 ± 107.4 mm (median, 79.3 mm), which equates to an approximate mean wound size of 3.73 cm × 3.73 cm or approximately 10.9 cm2 (median, 6.4 cm2).
Table I.
Mean baseline patient demographics and wound characteristics
| Characteristics |
|
|---|---|
| Patients | (n = 76) |
| Age, years | 63.6 ± 13.7 |
| Male | 46 (60.5) |
| Female | 30 (39.5) |
| BMI (kg/m2) | 36.3 ± 10.2 |
| BMI category | |
| 18.5 to <25.0 | 12 (15.8) |
| 25.0 to <30.0 | 13 (17.1) |
| ≥30.0 | 51 (67.1) |
| Target wound leg | |
| Right | 32 (42.1) |
| Left | 40 (52.6) |
| Both | 4 (5.3) |
| Wounds | (n = 80) |
|---|---|
| Circumferential | 21 (26.3) |
| Ulcer age at first encounter, weeks | 34.8 ± 51.8 |
| Median (IQR), weeks | 24.0 (11.5-40.0) |
| Hospitalization for target ulcer | 10 (12.5) |
| Previous procedure/treatment for target ulcer | 22 (27.5) |
| Previous skin graft for target ulcer | 5 (6.3) |
| Compliance with compression | 69 (86.3) |
| Duration of compression, weeks | 26.4 ± 35.9 |
| Signs of infection or bioburden | 14 (17.5) |
| GSV incompetence | 77 (96.3) |
| AASV incompetence | 18 (22.5) |
| Major perforator incompetence | 32 (40) |
| SSV incompetence | 25 (31.3) |
| Baseline VCSS (target leg) | 18.6 ± 4.7 |
AASV, Anterior accessory saphenous vein; BMI, body mass index; GSV, great saphenous vein; IQR, interquartile range; SSV, small saphenous vein; VCSS, Venous Clinical Severity Score.
Values are number (%) or mean ± standard deviation.
A history of VLUs in this group of patients was common, with study patients reporting a mean of 1.4 ± 1.8 previous ulcers. Of the 80 ulcers included in the study, 22 (27.5%) had been treated previously, with 5 (6.3%) receiving grafts or skin substitutes. At the time of enrollment, compliance with compression therapy was reported for 86.3% of wounds, with the mean duration of compression therapy 26.4 ± 35.9 weeks (interquartile range, 8.0-33.0 weeks). Twenty-eight patients (36.8%) reported taking pain medication regularly.
Procedure details
Polidocanol injectable microfoam was injected in a mean of 2.1 ± 1.6 sites at a mean volume of 3.9 ± 5.7 mL above the knee and 9.4 ± 4.5 mL below the knee. Fifty-two patients (68%) were treated in a single session. Postprocedure duplex ultrasound examinations were performed for 87.3% of wounds (69/79) at a mean of 8 ± 4 days after the injection procedure. At that visit, 45 of 70 wounds with site-reported status had occlusion of the target vein (64.3%). Twenty-four patients (31.6%) received additional 1% polidocanol injectable microfoam treatment. The mean duration between the first and additional treatment was 60.8 ± 80.3 days. Compliance with compression was reported in 94.9% of patients (75/79 wounds) at 1 week, 86.3% (63/73) at 12 weeks, and 73.8% (48/65) at 12 months after treatment.
Adverse events
No deep vein thrombosis related to the study procedure was reported. Two serious adverse events related to the polidocanol injectable microfoam were reported, with both events occurring in the same patient 2 days after the index procedure. One event was reported as asthenia and the other was pain in the extremity. The patient was a 60-year-old African American morbidly obese woman with multiple chronic comorbid conditions (anemia, cellulitis, diabetes, hypertension, and multiple open wounds of the lower leg) as well as an acute urinary tract infection and acute kidney injury/failure at the time of the events. The family reported the patient had severe leg pain for at least 1 year and was “getting worse,” but required adjustments of increased pain medication owing to resultant patient confusion. In addition to oral pain medication, the patient was receiving intravenous pain medication before dressing wound changes. Based on this information, the study sponsor assessed the generalized increased weakness or asthenia event as unlikely related to polidocanol treatment. The patient received oral antibiotics with local wound care and improved clinically. The event of pain was assessed as possibly related to the polidocanol treatment.
Ulcer healing and recurrence
By 12 weeks after treatment, 53.8% of wounds (43/80) had closed, and by 12 months 75% (60/80) had closed. By Kaplan-Meier analyses (Fig 1), the median time to ulcer closure was 89 days (95% CI, 62.0-117.0 days) or approximately 12.7 weeks. The progression of wound closure was paralleled by changes in the wound perimeter, as shown in Fig 2, which depicts the percent change from baseline in median wound perimeter over 12 weeks of follow-up. The degree of change in wound size varied from week to week depending on the subset of patients with perimeter measurements at that point in time. Relative to baseline, the median wound perimeter decreased by 16.3% (95% CI, –28.7 to 1.1) in the first 2 weeks and 27.0% (95% CI, –58.3 to 68.2) at 12 weeks, demonstrating a rapid healing response.
Fig 1.
Kaplan-Meier analysis of wound closure with 95% confidence interval (CI). Analysis based on the number of unhealed ulcers and time to closure.
Fig 2.
Percent change in median wound perimeter from baseline.
The prevalence of incompetent SSVs and major perforator veins at presentation (ie, incompetent veins not directly treated) was common both among wounds that did not heal (50.0% [10/20] and 35.0% [7/20], respectively) and among wounds that did heal (25.0% [15/60] and 41.7% [25/60], respectively) by 12 months. Thus, one-half of the unhealed wounds were associated with SSV incompetence at presentation, but a majority of wounds with SSV incompetence healed (60% [15/25]).
Kaplan-Meier analysis of wound recurrence is shown in Fig 3. Of the 60 healed wounds, 54 had closed at least 3 months before the patient's study exit and were included in the analysis of recurrence. Based on these 54 healed wounds, an estimated 88.9% (95% CI, 76.9-94.8) remained closed 12 weeks after closure and 87.0% (95% CI, 74.6-93.6) remained closed 12 months after closure by Kaplan-Meier analysis; the median was not reached in this analysis. The 12-month rate should be interpreted with caution owing to the low number of patients in follow-up at that time. Considering the seven recurring wounds only, the median time to recurrence was 37 days (interquartile range, 13-70 days).
Fig 3.
Kaplan-Meier analysis of wound recurrence with 95% confidence interval (CI). Wounds initially healed at least 3 months before study exit were included in the analysis. Wounds without recurrence were censored on the last day of study contact. Time represents weeks following the initial closure. Standard errors remained at less than 5% across all time points.
Venous symptoms and quality of life
The target leg VCSS decreased relative to baseline at both 12 weeks (mean change, –5.8; 95% CI, –7.1 to –4.5; n = 72) and 12 months (mean change, –10.0; 95% CI, –11.9 to –8.0; n = 56) after treatment in treated limbs. Relative to baseline, the mean numeric pain scores decreased (improved) by 41.0% at 12 weeks and 64.1% at 12 months after the procedure (Fig 4). The mean baseline EQ-5D-5L index was 0.65 ± 0.27 (n = 79). Among patients who had completed the questionnaire at both baseline and the follow-up time point, index scores increased (improved) to 0.72 ± 0.28 (95% CI, 0.65-0.78; n = 70) at 12 weeks and 0.73 ± 0.30 (95% CI, 0.64-0.82; n = 51) at 12 months, corresponding with index improvements (change from baseline) of 0.066 (95% CI, 0.011-0.122) and 0.072 (95% CI, 0.009-0.135) at 12 weeks and 12 months, respectively.
Fig 4.
Numeric Pain Rating Score. Patients reported pain at ulcer location on a scale of 0 to 10.
Discussion
The multicenter, open-label VIEW-VLU study presented a challenging patient population with longstanding recalcitrant ulcerations, as evidenced by the high average BMI, mean ulcer age of more than 8 months despite high reported compression compliance before study treatment, a high proportion of circumferential wounds, and large wound size. Yet, VLU perimeters decreased rapidly and one-half of these challenging wounds closed completely within 12 weeks of treatment. At 1 year, 75% of wounds were closed completely, in conjunction with reduced patient-reported pain and improved quality of life scores. Furthermore, the study showed a low incidence of recurrence, with only 13% of healed wounds reopening by 12 months after healing.
The EVRA trial showed that early endovenous ablation significantly decreased ulcer healing time from 82 days (deferred ablation group) to 56 days (early ablation group). Of note, within the early ablation group in EVRA, nearly one-half (49.6%) were treated with foam sclerotherapy alone and outnumbered those treated with endothermal ablation alone (31.7%) or mechanochemical ablation alone (2.2%). Although the median time to ulcer healing of 89 days in the VIEW-VLU study is longer than that reported in the EVRA trial,10 such a finding is not unexpected, given the more challenging wounds and patient population in the VIEW-VLU study compared with those in the EVRA trial,10 as summarized in Table II. Specifically, the VIEW-VLU study treated patients who were more obese (mean BMI 36.3 vs 30.3), with larger starting median ulcer size (6.4 cm2 vs 2.7 cm2), and older wounds (mean ulcer age 8.7 months vs 3.1 months), which suggests that these wounds may be recalcitrant to standard wound care measures and, therefore, more difficult to heal. The baseline VCSS and EQ-5D-5L index scores also reflected more severe symptoms and worse health-related quality of life, respectively, for patients in the VIEW-VLU study than were represented in EVRA,10 and both scores improved after treatment with 1% polidocanol injectable microfoam. The VIEW-VLU recurrence rate of 13% is similar to the 12-month ulcer recurrence rate of 12% reported for the compression and surgery arms in the Comparison of Surgery and Compression with Compression Alone in Chronic Venous Ulceration (ESCHAR) trial,19 which showed that surgical correction of superficial venous reflux in addition to compression helps to decrease VLU recurrence compared with compression treatment only (28% recurrence rate).20 With the benchmarks from EVRA and ESCHAR, VIEW-VLU adds to the evidence suggesting a wound healing benefit of endovenous chemical ablation.
Table II.
Key VIEW-VLU and EVRA9 patient characteristics at trial enrollment
| VIEW-VLU | EVRA | |
|---|---|---|
| Mean BMI, kg/m2 | 36.3 | 30.1 |
| Median ulcer size, cm2 | 6.4 | 2.7 |
| Mean ulcer age, months | 8.7 | 3.1 |
| Median VCSS | 18.5 | 16 |
| Mean EQ-5D-5L index | 0.65 | 0.73 |
BMI, Body mass index; EQ-5D-5L, EuroQol Five Dimension Five-level Questionnaire; VCSS, Venous Clinical Severity Score.
Insufficiency of the superficial venous system is a common underlying pathology for VLUs, with reports of refluxing veins in the area around the ulcer bed found in as many as 86% of ulcers.21 Reflux in the venules and microscopic veins has also been demonstrated in areas with skin damage and ulceration.22 Less invasive thermal and nonthermal endovenous ablation techniques have replaced surgery to correct venous reflux. Most of these techniques eliminate axial reflux, but do not address the terminal refluxing venous tributaries in the periulcer area. In accordance with the registry eligibility criteria, a majority of patients in the VIEW-VLU registry had GSV reflux. Treatment included both above and below-knee segments and treatment of the perivenous bed was also performed to ablate the refluxing terminal veins leading up to the ulcer bed itself. VIEW-VLU results demonstrate 1% polidocanol microfoam administered in the GSV including visible varicosities, effectively treats VLU and skin damage.
There are several limitations to this study. This is a single-arm prospective registry and is not a randomized comparative study. Inclusion eligibility required VLU duration of 3 or more months, but no eligibility criteria regarding compression therapy were applied. No study-specific standard for compression dressing beyond those stated in the 1% polidocanol microfoam instructions for use was instituted (ie, investigator's standard of care) and no information on the type of compression before or after treatment was collected; thus, the effects of compression therapy may be inconsistent across sites and patients. Likewise, wound care activities performed by local centers may have differed across patients in the study. Limited information on prior ulcer treatments was collected for the registry. Treated vein closure was not a study outcome; site assessment of occlusion was recorded for the registry only at the first post-treatment visit approximately 1 week after the procedure, and subsequent additional treatments were allowed. Although a computer tablet application facilitated wound image capture and recording of numeric pain scores between study visits, these assessments were sometimes missed. Core laboratory adjudication was not performed; however, an independent consultant systematically reviewed wound images for consistency in measurements and wound closure assessment. The wound recurrence assessment was limited by the available duration of follow-up; that is, recurrence could only be assessed among patients with initial wound healing sufficiently before study exit to allow a window of time for recurrence to be observed. This window was set to a minimum of 3 months between initial healing and study exit for analysis purposes, and few wounds were evaluable at longer term postclosure time points.
Treated veins included the GSV, AASV, and tributaries. These targets contrast with treatment in the EVRA trial, in which patients undergoing sclerotherapy did not have truncal veins treated and only had treatment of periulcer varicose veins and the subulcer plexus. In VIEW-VLU, perforator veins were not treated directly, and approximately 31% of the patients had SSV reflux, which is outside the 1% polidocanol injectable microfoam indication and, therefore, was not treated. Despite not treating the perforator and SSVs, high healing rates were still observed in this study compared with recent data.23 Indeed, major perforator or SSV incompetence at presentation was observed for more than one-quarter of wounds that healed. Treating all sources of venous hypertension may be desirable to improve healing,23 but these exploratory findings suggest that healing is possible even when the SSV or major perforator incompetence is not addressed directly. Deep vein obstruction and reflux data were not recorded for the registry and these characteristics could affect healing rates. Evaluation of the proximal veins for outflow obstruction was not done, which can also alter the treatment plan and outcomes.
In conclusion, VIEW-VLU registry results demonstrate that in a challenging patient population with a high BMI and large recalcitrant VLUs, treatment with 1% polidocanol microfoam was associated with a high ulcer healing rate with a low recurrence rate through 12 months. Future randomized trials may better delineate the role of polidocanol injectable microfoam in treating VLUs. Although further study is needed, the results suggest that 1% polidocanol injectable microfoam may show promise in healing VLUs and avoiding recurrence by targeting the terminal refluxing venous tributaries near the ulcer bed.
The authors thank Tissue Analytics (Baltimore, MD) for photograph analysis and Martin E. Wendelken, DPM (Advanced Planimetric Services, New York, NY), for independent wound image review (paid consultant). We thank the following Boston Scientific employees for their contributions: Tim Keo, MS (study management), Binal Patel, MPH (biostatistics), and Brett T. Cornell, PhD, and Elizabeth J. Davis, PhD (medical writing).
Author Contributions
Conception and design: MS, RK
Analysis and interpretation: MS, RK
Data collection: MS, SH, BC, KS, EF, JS, RK
Writing the article: MS, RK
Critical revision of the article: MS, SH, BC, KS, EF, JS, RK
Final approval of the article: MS, SH, BC, KS, EF, JS, RK
Statistical analysis: Not applicable
Obtained funding: Not applicable
Overall responsibility: MS
Collaborators: VIEW-VLU Investigators
Shao, Michael, Swedish Hospital, Northshore University Health System, Chicago, IL, USA.
Kolluri, Raghu, Ohio Health Heart and Vascular, Columbus, OH, USA.
Chan, Beverly, Vascular Health Bronte, Oakville, Ontario, Canada.
Ferris, Brian, Lake Washington Vascular, Bellevue, WA, USA.
Fukaya, Eri, Stanford University School of Medicine, Palo Alto, CA, USA.
Gagne, Paul, Vascular Experts, Darien, CT, USA.
Harlin, Stuart, University of Texas Health Sciences Center at Houston, Houston, TX, USA.
Fries, Richard, Mercy Health Cincinnati-West Hospital, Cincinnati, OH, USA.
Hedayati, Nasim, UC Davis, Davis, CA, USA.
Niazi, Khusrow, Emory University Hospital, Atlanta, GA, USA.
Santangelo, KathyLee, Totality, Oklahoma City, OK, USA.
Stoughton, Julianne, Massachusetts General Hospital, Boston, MA, USA.
Vasquez, Michael, Venous Institute of Buffalo, Amherst, NY, USA.
Zeig, Steven, Pines Clinical Research, Hollywood, FL, USA.
Footnotes
This study was funded by Boston Scientific Corporation, Marlborough, Massachusetts.
Author conflict of interest: M.S. is a consultant for Boston Scientific and Medtronic, and receives research support from BD. R.K. is a consultant, advisor, member of the DSMB, and CEC for Abbott, Avail Medical Systems, Boston Scientific, Inari, Medtronic, Mercador, Penumbra, Philips, Surmodics, and Thrombolex.
Additional material for this article may be found online at www.jvsvenous.org.
The editors and reviewers of this article have no relevant financial relationships to disclose per the Journal policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest.
Appendix
Additional material for this article may be found online at www.jvsvenous.org.
Contributor Information
Michael Y. Shao, Email: MShao@northshore.org.
VIEW-VLU Investigators:
Michael Shao, Raghu Kolluri, Beverly Chan, Brian Ferris, Eri Fukaya, Paul Gagne, Stuart Harlin, Richard Fries, Nasim Hedayati, Khusrow Niazi, KathyLee Santangelo, Julianne Stoughton, Michael Vasquez, and Steven Zeig
Appendix (online only)
Supplementary Table (online only).
VIEW-VLU study inclusion and exclusion criteria
| Inclusion criteria | Exclusion criteria |
|---|---|
|
|
AASV, Anterior accessory saphenous vein; ABI, ankle-brachial index; GSV, great saphenous vein; ICF, informed consent form; VLU, venous leg ulcer.
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