OBJECTIVE:Chronic venous disease affects > 40% of adults. The effectiveness of cyanoacrylate closure for the treatment of saphenous vein reflux compared with current global standard modalities remains unclear. The aim of this study was to assess patient centred and traditional venous outcomes comparing cyanoacrylate closure with surgical stripping and endothermal ablation, two global standards of care. METHODS:VenaSeal Spectrum randomised controlled trials (RCTs) are prospective, global, multicentre, 1:1 randomised studies evaluating the VenaSeal cyanoacrylate closure system for patients with chronic venous disease. Participants were enrolled in 23 centres across four continents. In the first RCT, 106 participants were randomly assigned to receive cyanoacrylate closure or surgical stripping. In the second RCT, 275 participants were randomly assigned to receive cyanoacrylate closure or endothermal ablation. The primary outcomes were patient satisfaction through 30 days using the peri- and post-procedural Venous Treatment Satisfaction Questionnaire (VenousTSQ), and proportion of saphenous reflux treated in each target vein. Adverse events were adjudicated by an independent committee and reported through 6 months. Traditional venous outcomes are evaluated as secondary outcomes. RESULTS:In both studies, baseline characteristics were similar between groups. Peri-procedural patient satisfaction at 30 days was greater in participants randomised to cyanoacrylate closure compared with surgical stripping (venous treatment satisfaction score 29.3 ± 4.94 vs. 25.0 ± 6.24, p = .001), but post-procedure patient satisfaction at 30 days and proportion of superficial truncal reflux treated were similar. There was no statistical difference detected in the three primary endpoints comparing cyanoacrylate closure and endothermal ablation. Overall adverse event rates were low, with the most common adverse events following cyanoacrylate being mild to moderate hypersensitivity, which was self limiting. CONCLUSION:Cyanoacrylate closure for treatment of saphenous reflux resulted in superior peri-procedural patient treatment satisfaction compared with surgical stripping. Patient satisfaction and proportion of superficial reflux treated after cyanoacrylate closure were comparable to endothermal ablation. CLINICAL TRIAL REGISTRATION:https://www. CLINICALTRIALS:gov, unique identifier NCT03820947.

BACKGROUND:Venous leg ulcers (VLUs) cause significant impairment to patients' quality of life (QoL) and up to 30% do not heal at 6 months. Decellularized dermis (DCD) allografts have been shown to be effective in improving healing rates of diabetic foot ulcers in RCTs. The DAVE RCT aimed to determine whether DCD is an effective, safe, and cost-effective treatment adjunct for VLUs. METHODS:This was a multicentre RCT performed in the UK. Patients with lower limb ulcers ≥18 years with VLU, venous incompetence on duplex ultrasound, an ankle : brachial pressure index ≥ 0.8 and an index VLU present for at least 3 months and ≥2 cm2 in size were included. Patients were randomized to either the intervention (DCD graft and standard of care) or control arm (standard of care alone). The primary outcome was the proportion of patients with a healed index ulcer at 12 weeks. RESULTS:From October 2019 to October 2022, 36 and 35 participants were randomized into the intervention and control arms respectively. Patient characteristics at baseline were similar between groups. Healing was recorded in 5.7% of the intervention group and 15.2% in the control group (OR 0.34, 95% c.i. 0.03 to 2.31). There were no significant differences in the secondary outcomes including the percentage change in ulcer area, time to healing, recurrence rates, and QoL. There were five serious adverse events attributed to DCD application. Early trial termination was advised after the interim data analysis due to a lower-than-expected primary outcome rate (11.3%). CONCLUSIONS:Decellularized dermis grafts did not improve healing rates of venous leg ulcers, although the trial was terminated early due to poor healing rates in both the intervention and control arms. Important clinical benefits or harms of decellularized dermis grafts could not be excluded due to the small sample size. TRIAL REGISTRATION:ISRCTN 21541209.

Acute deep venous thrombosis (DVT) is a common health problem, affecting millions of patients in Europe and the United States annually. Europe and US national clinical practice guidelines are formulated by evaluation of the available scientific evidence, with expert opinion to create pragmatic guidance for the optimal patient management, representing the best available knowledge at the time of publication, and providing the best evidence-based recommendations for vascular patient care and venous pathologies. We here focus on the novel recommendations proposed by European and US guidelines for acute DVT, denoting main differences between the two panels. This review gives vascular surgeons the opportunity to identify the key points of the two largest Vascular Committees guidelines, in order to use them and offer their best individualized treatment approach to the specific patient's anatomy, lesion, and history.

Objective Chronic venous disease affects over 25% of adults in developed countries. It is usually a progressive disease, if left untreated, can lead to advanced disease such as venous ulceration. The VenaSeal Spectrum Program compares the VenaSeal™ closure system (VenaSeal) to the global standards of care for chronic venous disease: endothermal ablation and surgical stripping. It also investigates VenaSeal’s utility for patients with venous leg ulcers. A key component of this clinical program is to measure and quantify patient satisfaction of treatments related to discomfort, healing time, and effectiveness, which often has been overlooked in chronic venous disease research. This paper describes the rationale and design of the VenaSeal Spectrum Program for patients with chronic venous disease. Methods VenaSeal Spectrum is a prospective, post-market, clinical trial program reporting outcomes from the peri-procedural period through 5 years following treatment with VenaSeal. VenaSeal Spectrum has enrolled 506 participants at 32 sites in 10 countries requiring treatment for symptomatic Clinical, Etiological, Anatomical, and Pathophysiological Classification (CEAP) 2–6 chronic venous disease involving the truncal saphenous vein(s). The program is composed of three studies. Two randomized controlled trials compare VenaSeal ablation with either surgical stripping or endovenous thermal ablation in patients with symptomatic CEAP 2-5 disease. A single-arm prospective study investigates participants with active venous leg ulcers (VLUs; CEAP 6) treated with VenaSeal. The unique primary endpoints for both randomized trials include both peri- and post-procedural patient treatment satisfaction measured by a new questionnaire (VenousTSQ) at 30 days post-procedure and elimination of clinically relevant superficial truncal reflux in the target vein at index procedure. The primary endpoint for the VLU study is time to ulcer healing through 12 months. Secondary endpoints, which are more familiar to clinicians in this disease space, include time to return to work, complication rates, patient-reported outcome measures, and closure rates. Conclusions VenaSeal Spectrum is a rigorously designed clinical study program with a large study population and unique patient-centric endpoints after treatment with VenaSeal for early to advanced symptomatic chronic venous disease. The studies will report safety, effectiveness and patient experience outcomes including two new primary endpoints assessing the specific needs of patients with venous insufficiency from the peri-procedural period through 5-year follow-up.

OBJECTIVE:The endovascular treatment of venous obstruction has expanded significantly in recent years. Best practices for optimal patient outcomes are not well established and the evidence base is poor. The purpose of this study was to obtain consensus on management criteria for patients with lower extremity venous outflow obstruction.METHODS:The study was conducted as a two round Delphi consensus. Statements addressed imaging, symptoms and other baseline measures, differential diagnosis, treatment algorithm, indications for stenting, inflow and outflow assessment, successful procedural outcomes, post-procedure therapies and stent surveillance, and clinical success factors. Statements were prepared by six expert physicians (round 1, 40 statements) and an expanded panel of 24 physicians (round 2, 80 statements) and sent to a pre-identified group of venous experts who met qualifying criteria. A 9 point Likert scale was used and consensus was defined as ≥ 70% of respondents rating a statement between 7 and 9 (agreement) or between 1 and 3 (disagreement). Round 1 results were used to guide rewording and splitting compound statements for greater clarity in round 2.RESULTS:In round 1, 75 of 110 (68%) experts responded, and 91 of 121 (75%) experts responded in round 2. Round 1 achieved consensus in 32/40 (80%) statements. Consensus was not reached in the treatment algorithm section. Round 2 achieved consensus in 50/80 (62.5%). Statements reaching consensus were imaging (2/3, 66%), symptoms and other baseline measures (12/24, 50%), differential diagnosis (2/8, 25%), treatment algorithm (10/17, 59%), indications for stenting (10/10, 100%), inflow and outflow assessment (2/2, 100%), procedural outcomes (2/2, 100%), post-procedure therapies and stent surveillance, (5/7, 71%), and clinical success factors (5/7, 71%).CONCLUSION:This study demonstrated that considerable consensus was achieved between venous experts on the optimal management of lower extremity venous outflow obstruction. There were multiple domains where consensus is lacking, highlighting important areas for further investigation and research.

Introduction Hospital-acquired thrombosis (HAT) is defined as any venous thromboembolism (VTE)-related event during a hospital admission or occurring up to 90 days post discharge, and is associated with significant morbidity, mortality and healthcare-associated costs. Although surgery is an established risk factor for VTE, operations with a short hospital stay (<48 hours) and that permit early ambulation are associated with a low risk of VTE. Many patients undergoing short-stay surgical procedures and who are at low risk of VTE are treated with graduated compression stockings (GCS). However, evidence for the use of GCS in VTE prevention for this cohort is poor.Methods and analysis A multicentre, cluster randomised controlled trial which aims to determine whether GCS are superior in comparison to no GCS in the prevention of VTE for surgical patients undergoing short-stay procedures assessed to be at low risk of VTE. A total of 50 sites (21 472 participants) will be randomised to either intervention (GCS) or control (no GCS). Adult participants (18–59 years) who undergo short-stay surgical procedures and are assessed as low risk of VTE will be included in the study. Participants will provide consent to be contacted for follow-up at 7-days and 90-days postsurgical procedure. The primary outcome is the rate of symptomatic VTE, that is, deep vein thrombosis or pulmonary embolism during admission or within 90 days. Secondary outcomes include healthcare costs and changes in quality of life. The main analysis will be according to the intention-to-treat principle and will compare the rates of VTE at 90 days, measured at an individual level, using hierarchical (multilevel) logistic regression.Ethics and dissemination Ethical approval was granted by the Camden and Kings Cross Research Ethics Committee (22/LO/0390). Findings will be published in a peer-reviewed journal and presented at national and international conferences.Trial registration number ISRCTN13908683.

Methods: This was an open, multicentre, randomized controlled trial. Patients with intermittent claudication attending vascular surgery outpatient clinics were randomized (1:1) to receive either neuromuscular electrical stimulation (NMES) or not in addition to local standard care available at study centres (best medical therapy alone or plus supervised exercise therapy (SET)). The objective of this trial was to investigate the clinical efficacy of an NMES device in addition to local standard care in improving walking distances in patients with claudication. The primary outcome was change in absolute walking distance, measured by a standardized treadmill test at 3 months. Secondary outcomes included intermittent claudication (IC) distance, adherence, quality of life, and haemodynamic changes. Results: Of 200 participants randomized, 160 were included in the primary analysis (intention to treat, Tobit regression model). The square root of absolute walking distance was analysed (due to a right-skewed distribution) and, although adjunctive NMES improved it at 3 months, no statistically significant effect was observed. SET as local standard care seemed to improve distance compared to best medical therapy at 3 months (3.29 units; 95 per cent c.i., 1.77 to 4.82; P < 0.001). Adjunctive NMES improved distance in mild claudication (2.88 units; 95 per cent c.i., 0.51 to 5.25; P = 0.02) compared to local standard care at 3 months. No serious adverse events relating to the device were reported. Conclusion: Supervised exercise therapy is effective and NMES may provide further benefit in mild IC. This trial was supported by a grant from the Efficacy and Mechanism Evaluation Program, a Medical Research Council and National Institute for Health and Care Research partnership. Trial registration: ISRCTN18242823.

BACKGROUND:Established condition-specific patient-reported outcome measures for varicose veins are limited to the measurement of health status and function. A treatment satisfaction measure is needed to understand patient satisfaction with different treatment options. The aim of this study was to design a Venous Treatment Satisfaction Questionnaire (VenousTSQ) that would be ready for large-scale data collection and psychometric evaluation.METHODS:Relevant items were selected from the -TSQ Item Library and new items were designed where necessary. A draft VenousTSQ was prepared using the existing AneurysmTSQ as a template. Fifteen interviews were conducted from 4 days to 16 months after the procedure. The interviews were designed to elicit important sources of satisfaction or dissatisfaction before completion of draft questionnaires. The VenousTSQ drafts were modified between sets of interviews until no further changes were required.RESULTS:The final VenousTSQ consists of two questionnaires: VenousTSQ early (VenousTSQe) and VenousTSQ status (VenousTSQs). Items that need be asked only once are in the VenousTSQe, whereas those that can usefully be asked more than once are in the VenousTSQs. Of the 16 unique items forming the VenousTSQ, 12 were from the -TSQ Item Library. Only 1 of these 12 required significant modification.CONCLUSIONS:The VenousTSQ represents a condition-specific psychological outcome measure for varicose veins, enabling patient satisfaction or dissatisfaction with such treatments to be measured. Large-scale data collection is under way to establish optimal scoring, quantitative validity, and reliability of the VenousTSQ.

Introduction Endovenous therapy is the first choice management for symptomatic varicose veins in NICE guidelines, with 56–70 000 procedures performed annually in the UK. Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a known complication of endovenous therapy, occurring at a rate of up to 3.4%. Despite 73% of UK practitioners administering pharmacological thromboprophylaxis to reduce VTE, no high-quality evidence supporting this practice exists. Pharmacological thromboprophylaxis may have clinical and cost benefit in preventing VTE; however, further evidence is needed. This study aims to establish whether when endovenous therapy is undertaken: a single dose or course of pharmacological thromboprophylaxis alters the risk of VTE; pharmacological thromboprophylaxis is associated with an increased rate of bleeding events; pharmacological prophylaxis is cost effective.Methods and analysis A multi-centre, assessor-blind, randomised controlled trial (RCT) will recruit 6660 participants from 40 NHS and private sites across the UK. Participants will be randomised to intervention (single dose or extended course of pharmacological thromboprophylaxis plus compression) or control (compression alone). Participants will undergo a lower limb venous duplex ultrasound scan at 21–28 days post-procedure to identify asymptomatic DVT. The duplex scan will be conducted locally by blinded assessors. Participants will be contacted remotely for follow-up at 7 days and 90 days post-procedure. The primary outcome is imaging-confirmed lower limb DVT with or without symptoms or PE with symptoms within 90 days of treatment. The main analysis will be according to the intention-to-treat principle and will compare the rates of VTE at 90 days, using a repeated measures analysis of variance, adjusting for any pre-specified strongly prognostic baseline covariates using a mixed effects logistic regression.Ethics and dissemination Ethical approval was granted by Brent Research Ethics Committee (22/LO/0261). Results will be disseminated in a peer-reviewed journal and presented at national and international conferences.Trial registration number ISRCTN18501431.

Background Peripheral arterial disease is common and associated with increased cardiovascular morbidity and mortality. While patients with peripheral arterial disease are known to benefit from supervised exercise therapy, it is not always available. Neuromuscular electrical stimulation devices may offer a similar benefit. A randomised controlled trial was required to ascertain whether such devices can benefit patients who receive supervised exercise therapy and those who do not. Objective(s) The primary objective was to assess the mean difference in absolute walking distance at 3 months in intermittent claudication patients receiving either a neuromuscular electrical stimulation device and local standard care (intervention), or local standard care alone (control). Design A pragmatic, multicentre, randomised controlled trial stratified by centre. Setting Secondary-care National Health Service hospitals in the United Kingdom. Participants Patients aged ≥18 years, with a diagnosis of intermittent claudication according to the Edinburgh Claudication Questionnaire and ankle–brachial pressure index (or stress test), without contraindications to neuromuscular electrical stimulation were deemed eligible to partake. Interventions Participants were randomised 1 : 1 to either local standard care or local standard care and neuromuscular electrical stimulation. Due to the nature of the intervention, it was unfeasible to blind the research nurse or participant to the study allocation. Main outcome measures The primary outcome measure was absolute walking distance measured by treadmill testing at 3 months. Secondary outcomes included change in initial claudication distance, quality of life, compliance with interventions and haemodynamic assessments. Results Two hundred patients underwent randomisation, with 160 patients having analysable primary outcome data for the intention-to-treat analysis intervention (n = 80); control (n = 80). As the data were right-censored, a Tobit regression model was used to analyse the primary outcome, utilising the square root of the absolute walking distance to accommodate the skewed data. However, as this made the data difficult to interpret, a Tobit regression model using raw absolute walking distance data was used as well. Neuromuscular electrical stimulation improved the difference in absolute walking distance at 3 months but this was not statistically significant (square root of absolute walking distance: 0.835 units, 95% confidence interval −0.67 to 2.34 units; p = 0.28/absolute walking distance raw data: 27.18 m, 95% confidence interval −26.92 to 81.28 m; p = 0.323). Supervised exercise therapy participants showed a markedly improved absolute walking distance compared with patients receiving best medical therapy only at 3 months (square root of absolute walking distance: 3.295 units 95% confidence interval 1.77 to 4.82; p < 0.001/absolute walking distance raw data: 121.71 m, 95% confidence interval 67.32 to 176.10; p ≤ 0.001). Neuromuscular electrical stimulation significantly improved absolute walking distance at 3 months for mild claudicants (square root of absolute walking distance: 2.877 units, 95% confidence interval 0.51 to 5.25; p = 0.019/absolute walking distance raw data: 120.55 m, 95% confidence interval 16.03 to 225.06; p = 0.03) compared to the control arm. This was an unplanned (post hoc) analysis. There were no clear differences in mechanistic measurements between the two treatment groups over the follow-up period. Serious adverse events were evenly reported between the two groups; all being classified as either not related or unlikely to be related to the study device. Limitations Absolute walking distance was used as the primary outcome measure; there was a large range of baseline distances in both groups with right-skewed distribution. We did not stratify by baseline absolute walking distance for the primary outcome analysis. Additionally, only 160 patients had analysable primary outcome data due to missing treadmill data. Conclusions Supervised exercise therapy is an effective treatment for intermittent claudication. Neuromuscular electrical stimulation appears to be beneficial as an adjunct to supervised exercise therapy and on its own in mild claudicants. Future work Further studies are needed to confirm the effectiveness of neuromuscular electrical stimulation in combination with supervised exercise therapy, and in mild to moderate claudicants in a larger sample size. Study registration This trial is registered as ISRCTN18242823. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership (project number 15/180/68). This will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 2. See the NIHR Journals Library website for further project information. Infrastructure support for this research was provided by the NIHR Imperial Biomedical Research Centre (BRC) (with others, e.g. NIHR Imperial CRF, Imperial College ECMC, NIHR Imperial PSTRC, NIHR London MIC, etc.).

Venous leg ulceration is common, distressing for patients, and a major burden on healthcare services around the world. The mainstay of treatment is compression therapy, which has been shown to improve ulcer healing. Incompetence of superficial veins is common in patients with lower extremity wounds. The ESCHAR study showed that the traditional surgical approach for superficial reflux reduced venous ulcer recurrence. However, modern venous practice in most the United States and European centers has moved away from surgical stripping and endovenous interventions are now the first-line approach. These minimally invasive procedures may be more appropriate for the elderly and often frail population, who may not be fit or willing to undergo surgery under general anesthesia. The Early Venous Reflux Ablation (EVRA) study was designed to evaluate the role of early endovenous ablation in addition to compression therapy in the treatment of C6 disease. In this chapter, the design, clinical outcomes, and implementation challenges of the EVRA study are summarized.

The authors regret there was a mistake in Figure 6 and 13. In Figure 6, it should read ‘Compression’ for oedema, to include inelastic compression as well (green box); in Figure 13, the pressure at the ankle should read ‘≤ 40 mm Hg’, for small and recent onset ulcer (yellow box):

Chronic obstruction of the iliac veins or inferior vena cava can occur as a result of deep vein thrombosis, or owing to extrinsic compression in nonthrombotic iliac vein lesions (NIVLs). This obstruction can manifest as post-thrombotic syndrome (PTS) after deep vein thrombosis or as chronic venous disease (CVD) in NIVL. Little evidence exists to support the use of deep venous stents in established PTS or NIVLs, and the evidence for its use in the prevention of PTS is inconclusive. A provisional health economic analysis over 5 years found that the incremental cost-effectiveness ratio of stenting versus no stenting over a 5-year period was between £7,500 and £52,000 per quality-adjusted life-year for treatment of established PTS.

Compared with the 2015 version of the guidelines on the management of chronic venous disease (CVD),1 the global structure of the document has been modified considerably in an attempt to make it more practical and user friendly. Special subsections on management strategy with accompanying flowcharts have been added to the different chapters.•An extensive chapter has been entirely dedicated to superficial venous incompetence. A new subsection on evidence supporting endovenous non-thermal ablation has been included. A new subsection on incompetence of perforating veins has been added, as well as a subsection on practical strategies for special anatomical presentations. The management of recurrent varicose veins is discussed at the end of this chapter.•Deep venous pathology is discussed in a separate chapter, with an emphasis on the increasing evidence in the field of managing iliofemoral and iliocaval obstruction. In addition, new topics in this chapter are the combination of superficial and deep venous problems, aneurysms of the deep veins and popliteal vein entrapment syndrome.•An entirely new chapter has been dedicated to the management of patients with venous leg ulcers.•A new chapter describes the management of patients with varicose veins, related to underlying pelvic venous disorders.•A new chapter considers special patient characteristics and their potential influence on management strategy.•Gaps in evidence and future perspectives are briefly discussed in a separate chapter.•A lay summary of the guidelines provides useful information for patients.

The endovascular treatment of venous obstructive disease has expanded significantly in recent years. However, best practices for optimal patient outcomes are not well established outside of the expert community and the evidence base is poor. The purpose of this study was to determine the level of consensus on statements regarding best practices. The study was conducted as a two round Delphi consensus. Statements for the first round were prepared by six expert physicians (round 1) and an expanded panel of 24 physicians (round 2) and sent to a preidentified group of venous experts who met qualifying criteria for each round. The statements were based on clinical scenarios covering the areas of imaging, clinical symptoms and baseline measures, differential diagnosis, treatment algorithm, indications for stenting, inflow/outflow assessment, successful procedural outcomes, postprocedure care and follow-up, and successful clinical outcomes. There were 39 and 80 statements in rounds 1 and 2, respectively. Respondent agreement was assessed using a 9-point Likert scale (agreed to disagreed) and a “cannot assess” option were used for each question. Consensus was defined as 70% respondents rating a statement 7 to 9 (signifying agreement) or 1 and 3 (signifying disagreement). The results of the first round were used to guide rewording and splitting compound statements for the greater clarity for the second round. The first round survey received a 68% response rate (75/110), and the second round received a 75% response rate (91/121). Respondents identified themselves as vascular surgeons (52.8%), interventional radiologists (33.0%), interventional cardiologists (8.8%), and other (5.5%) and represented the Americas (73.6%), Europe/Middle East (18.7%), and Asia Pacific (7.7%). Round 1 achieved consensus in 32/39 (82%) statements. Consensus was not reached in the treatment algorithm section. Round 2 achieved consensus in 50/80 (62.5%). The number of statements reaching consensus in the following areas were as follows: imaging (2/3 [66%]), clinical symptoms and baseline measures (12/24 [50%]), differential diagnosis (2/8 [25%]), treatment algorithm (10/17 [59%]), indications for stenting (10/10 [100%]), inflow/outflow assessment (2/2 [100%]), procedural outcomes (2/2 [100%]), postprocedure care (5/7 [71%]), and successful clinical outcomes (5/7 [71%]). This study demonstrated that while there are several areas where venous experts agree on the assessment and management of venous outflow obstruction, there are multiple domains where consensus was not achieved. This underlines that treating venous disease remains a controversial area and requires focused and coordinated research efforts across specialties to answer a number of unresolved clinical questions. The Delphi consensus has identified those areas in which these efforts should be focused.

Routine coagulation monitoringYesNo No No No VKA ¼ vitamin K antagonist; INR ¼ international normalised ratio; NA ¼ not applicable; P-gp ¼ P-glycoprotein; CYP ¼ cytochrome P450; o.d.¼ once daily; b.d.¼ twice daily * Bioavailability of rivaroxaban calculated for 10 mg dose.

Introduction Up to 50% of patients develop post-thrombotic syndrome (PTS) after an above knee deep vein thrombosis (DVT). The aim of the study was to determine the effect of graduated compression stockings in preventing PTS after DVT.Methods and analysis Pragmatic, UK multicentre randomised trial in adults with first above knee DVT. The standard of care arm is anticoagulation. The intervention arm will receive anticoagulation plus stockings (European class II, 23–32 mm Hg compression) worn for a median of 18 months. The primary endpoint is PTS using the Villalta score. Analysis of this will be through a time to event approach and cumulative incidence at median 6, 12 and 18 months. An ongoing process evaluation will examine factors contributing to adherence to stockings to understand if and how the behavioural interventions were effective.Ethics and dissemination UK research ethics committee approval (reference 19/LO/1585). Dissemination though the charity Thrombosis UK, the Imperial College London website, peer-reviewed publications and international conferences.Trial registration number ISRCTN registration number 73041168.

OBJECTIVE:The aim of this study was to identify potential biomarkers predictive of healing or failure to heal in a population with venous leg ulceration.SUMMARY BACKGROUND DATA:Venous leg ulceration presents important physical, psychological, social and financial burdens. Compression therapy is the main treatment, but it can be painful and time-consuming, with significant recurrence rates. The identification of a reliable biochemical signature with the ability to identify nonhealing ulcers has important translational applications for disease prognostication, personalized health care and the development of novel therapies.METHODS:Twenty-eight patients were assessed at baseline and at 20 weeks. Untargeted metabolic profiling was performed on urine, serum, and ulcer fluid, using mass spectrometry and nuclear magnetic resonance spectroscopy.RESULTS:A differential metabolic phenotype was identified in healing (n = 15) compared to nonhealing (n = 13) venous leg ulcer patients. Analysis of the assigned metabolites found ceramide and carnitine metabolism to be relevant pathways. In this pilot study, only serum biofluids could differentiate between healing and nonhealing patients. The ratio of carnitine to ceramide was able to differentiate between healing phenotypes with 100% sensitivity, 79% specificity, and 91% accuracy.CONCLUSIONS:This study reports a metabolic signature predictive of healing in venous leg ulceration and presents potential translational applications for disease prognostication and development of targeted therapies.