Early Venous Reflux Ablation Ulcer Trial

Not Applicable

Completed

• Conditions: Venous Leg Ulcer
• Interventions: Procedure: Delayed endovenous intervention; Procedure: Early endovenous ablation

• Registration Number: NCT03286140
• Lead Sponsor: Imperial College London

Brief Summary

The EVRA study evaluates the effects of early endovenous ablation on ulcer healing in patients with chronic venous ulceration. Half the patients are randomised to receive early endovenous ablation (within 2 weeks) and half to standard care

Detailed Description

A large number of patients (around 1% of the adult population) suffer from an ulcer (break in the skin surface) near the ankle. In most people, such an injury should heal up within a week or two. However, when there is an underlying problem with the skin, ulcers do not heal and may result in longstanding (chronic), painful, smelly and embarrassing wounds. The ulcers are often due to varicose veins in the legs, which can cause skin breakdown and ulcer formation. To get the ulcer to heal, the current best treatment is to wear a tight compression bandage with multiple layers, with which about 60% of these ulcers will heal within 24 weeks. There is evidence that treatment of the varicose veins by surgery will prevent the ulcer from returning after it has healed. Recent studies have suggested that newer techniques of treating varicose veins, such as injecting a medicine into the varicose vein (sclerotherapy) or treating the vein with heat ablation to seal it (using laser or radiofrequency), in an outpatient setting may help the ulcers to heal more quickly and (like surgery) reduce the chance of the ulcer coming back. These techniques can be carried out in the outpatient setting and are much better tolerated by patients in comparison to surgery. The aim of this study is to see whether early treatment of varicose veins using sclerotherapy or heat ablation helps with healing.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2013-09-01
• Study First Submitted: 2017-09-04
• Study First Submitted QC: 2017-09-13
• Study First Posted: 2017-09-18
• Primary Completion: 2019-03-31
• Study Completion: 2019-03-31
• Results First Submitted: 2022-04-12
• Status Verified: 2024-05
• Results First Submitted QC: 2024-05-13
• Last Update Submitted: 2024-05-13
• Results First Posted: 2024-05-20
• Last Update Posted: 2024-05-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

• Current leg ulceration of greater than 6 weeks, but less than 6 months duration
• Able to give informed consent to participate in the study after reading the patient information documentation
• Patient age > 18 years
• Ankle Brachial Pressure Index (ABPI) ≥ 0.8
• Superficial venous disease on colour duplex assessment deemed to be significant enough to warrant ablation by the treating clinician (either primary or recurrent venous reflux)

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Exclusion Criteria

• Presence of deep venous occlusive disease or other conditions precluding superficial venous intervention (at the discretion of local research team)
• Patients who are unable to tolerate any multilayer compression bandaging / stockings will be excluded. However, concordance with compression therapy can be variable for patients at different times. Patients who are generally compliant with compression, but unable to tolerate the bandages for short periods will still be eligible to inclusion. A period of non-compliance with compression bandages will not be considered a protocol violation, but a normal variation within the spectrum of 'standard therapy'.
• Inability of the patient to receive prompt endovenous intervention by recruiting centre
• Pregnancy (female participants of reproductive age will be eligible for inclusion in the study, subject to a negative pregnancy test prior to randomisation)
• Leg ulcer of non-venous aetiology (as assessed by responsible clinician)
• Patient deemed to require skin grafting

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard therapy arm	Delayed endovenous intervention	Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed)
Early arm	Early endovenous ablation	Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy

Primary Outcome Measures

Name	Time	Method
Time to Ulcer Healing From Date of Randomisation to Date of Healing up to 365 Days	time from date of randomisation to date of healing up to 365 days	For the purposes of this study, ulcer healing is defined as complete re-epithelialisation of all ulceration on the randomised (reference) leg in the absence of a scab (eschar) with no dressing required.

Secondary Outcome Measures

Name	Time	Method
EuroQol-5 Dimensions (EQ-5D)	6 weeks post randomisation, 6 months, 12 months	The EuroQol-5 Dimensions (EQ-5D) is a widely recognised, generic tool to measure health outcomes and has been validated in a variety of patient groups, including those with venous leg ulcers. The EQ-5D questionnaire comprises two sections; the first assesses the participant's mobility, self-care, ability to perform usual activities, pain/discomfort and anxiety/depression levels, and the second records the participant's self-rated health on a vertical score of 0 to 100.
Health Economic Assessment	Baseline, 6 weeks, 6 months, 12 months	A within-RCT cost effectiveness analysis will be carried out based on the data collected in the trial, Resource use items in hospital and community care related to the treatment of venous ulceration or complications will be recorded for each patient at each follow-up. Resource use will be multiplied by UK unit costs obtained from published literature, HRG costs, and manufacturers' list prices to calculate overall costs. A standard tariff will be applied for each bandage change. Utilities (QALYs) will be calculated from the EQ-5D questionnaire administered to patients
Clinical Success - VCSS	at 6 weeks	The Venous Clinical Severity Score (VCSS) is a component of the Venous Severity Scoring System designed in 2000 by an ad hoc American Venous Forum committee consensus, in order to compliment the CEAP classification and quantify the severity of disease and subsequent improvement or decline. The VCSS has 10 components (pain, varicose veins, venous oedema, skin pigmentation, inflammation, induration, compression used and active ulcer, duration, number and size), each with four categories assigned values of 0-3. The overall scores can range from 0 (lowest severity) to 30 (highest severity).
Clinical Success - Complications	up to 12 months	Number of complications related to the endovenous intervention
Percentage of Participants With Ulcer Healing	24 weeks & time to ulcer healing up to 365 days	Healing rate will be reported at 24 weeks using the percentage of participants with a healed ulcer
Ulcer Recurrence / Ulcer Free Time	Up to 12 months (and with the extension, up to 5 years (median approximately 3.7 years))	Will be calculated up to 1 year for each study arm and with the extension, up to 5 years (median approximately 3.7 years). This will allow a very practical and easily understood assessment of the clinical difference between the 2 arms of the study. This will also allow comparison with other studies that have reported this outcome. In order to facilitate accurate calculation of reoccurrence / ulcer free time, clinical follow up will be continued after ulcer healing up to 1 year after randomisation.
Clinical Success - Presence of Residual / Recurrent Reflux in the Veins	at 6 weeks	The presence of residual / recurrent varicose veins remaining on the venous duplex. Any reflux detected by the vascular scientists (as per local scanning policies) is recorded as presence of residual reflux and therefore considered incomplete clinical success. No presence of residual reflux is considered clinical success. (Clinical-Etiology-Anatomy-Pathophysiology) ranges from C0 which means absolutely no venous disease that can be seen or felt in the legs to C6 which means an open and active venous leg ulcer. For this outcome measure: Healed venous leg ulcer (C5), Active venous leg ulcer (C6).
Quality Of Life Questionnaire up to 365 Days	6 weeks post randomisation, 6 months, 12 months	Disease specific (AVVQ) quality of life; The Aberdeen Varicose Vein Questionnaire (AVVQ) is a validated patient-reported disease-specific health questionnaire to assess quality of life in patients with varicose veins. The AVVQ comprises a diagram on which patients draw on their varicose veins and a questionnaire with 12 questions, half of which require a response for each leg. The scores range from 0 to 100 (no effect to severe effect).
Generic (SF-36) Quality of Life Assessment	6 weeks post randomisation, 6 months, 12 months	Generic (SF-36) quality of life assessment; The Short Form questionnaire-36 items (SF-36) is a generic quality-of-life tool used to determine people's physical and mental health. It has been validated in many patient groups, including those with varicose veins. The physical domain measures physical functioning, physical role limitations, body pain and general health, whereas the mental dimension measures vitality, social functioning, mental health role limitations and general mental health. Two separate scores are produced (separate physical/mental component summary scores), in addition to the eight separate domain scores. Each score is measured on a scale of 0 to 100 (worst to best). Scores represent the percentage of total possible score achieved.

Trial Locations

Locations (1)

Imperial College London; 🇬🇧 London, United Kingdom