Early Venous Reflux Ablation Ulcer Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomised Clinical Trial to Compare Early Versus Delayed Endovenous Treatment of Superficial Venous Reflux in Patients With Chronic Venous Ulceration

Conditions
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Venous Leg Ulcer

Intervention / Treatment
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* Procedure: Early endovenous ablation
* Procedure: Delayed endovenous intervention


Participation Criteria
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Eligibility Criteria
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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) 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The EVRA ulcer trial is a pragmatic; multicentre randomised clinical trial with participants randomised1:1 to either: 'Standard' therapy consisting of multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard therapy
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard therapy arm<br>Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) | Procedure: Delayed endovenous intervention<br> <br> |
| Experimental: Early arm<br>Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy | Procedure: Early endovenous ablation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to ulcer healing | 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. | time from date of randomisation to date of healing within the 12 month study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ulcer Healing Rate | Healing rate will be reported at 24 weeks in addition to time to ulcer healing to allow comparison with other published studies | 24 weeks & time to ulcer healing within the 12 month study period | 
| Ulcer recurrence / Ulcer Free Time | 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. | Up to 12 months (and with the extension, up to 5 years (median approximately 3.7 years)) | 
| Quality Of Life Questionnaire | Disease specific (AVVQ) quality of life | 6 weeks post randomisation, 6 months, 12 months and at one time point between October 2018 and March 2019 | 
| Quality Of Life Questionnaire | Generic (SF36) quality of life assessment | 6 weeks post randomisation, 6 months, 12 months and at one time point between October 2018 and March 2019 | 
| Quality Of Life Questionnaire | Generic (EQ5D )quality of life assessment | 6 weeks post randomisation, 6 months, 12 months and at one time point between October 2018 and March 2019 | 
| Health Economic Assessment | 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 | Baseline, 6 weeks, 6 months, 12 months | 
| Clinical Success - Presence of residual / recurrent varicose veins | The presence of residual / recurrent varicose veins remaining on the venous duplex | at 6 weeks | 
| Clinical Success - VCSS | The Venous Clinical Severity Score (VCSS) | at 6 weeks | 
| Clinical Success - Complications | Incidence of complications related to the endovenous intervention | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endovenous ablation