Early Venous Reflux Ablation Ulcer Trial (EVRA)

• ClinicalTrials.gov Identifier: NCT03286140
• Recruitment Status: Completed
• First Posted: September 18, 2017
• Last Update Posted: July 11, 2019
• Sponsor: Imperial College London
• Collaborators: University of Birmingham; Universidad de Granada; University of Manchester; University of Warwick
• Information provided by (Responsible Party): Imperial College London

Study Description

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

Condition or disease	Intervention/treatment	Phase
Venous Leg Ulcer	Procedure: Early endovenous ablation; Procedure: Delayed endovenous intervention	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 450 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention Model Description

The EVRA ulcer trial is a pragmatic; multicentre randomised clinical trial with participants randomised1:1 to either:

1. 'Standard' therapy consisting of multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed)
2. Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard therapy

• Masking: Single (Outcomes Assessor)
• Masking Description: Blinded assessment of ulcer healing photos
• Primary Purpose: Treatment
• Official Title: A Randomised Clinical Trial to Compare Early Versus Delayed Endovenous Treatment of Superficial Venous Reflux in Patients With Chronic Venous Ulceration
• Actual Study Start Date: September 1, 2013
• Actual Primary Completion Date: March 31, 2019
• Actual Study Completion Date: March 31, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Time to ulcer healing [ Time Frame: time from date of randomisation to date of healing within the 12 month study period ]
   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 :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United Kingdom

Imperial College London

London, United Kingdom, W68RF

Sponsors and Collaborators

Imperial College London

University of Birmingham

Universidad de Granada

University of Manchester

University of Warwick

Investigators

• Study Chair: Gerard Stansby; Newcastle University
• Study Chair: Julie Brittenden; University of Glasgow

More Information

Additional Information:

Trial website 

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT03286140
• Other Study ID Numbers: 13HH0722
• First Posted: September 18, 2017
• Last Update Posted: July 11, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Plan Description

At completion of the study, data will be shared in accordance with the NIHR HTA guidance on study outputs as per the research contract between the secretary of state for health research and Imperial College London. Only anonymised data will be shared under the terms of the consent forms.

Data and associated documentation will be available to users only under a data-sharing agreement that provides for the following:

1. A commitment to using the data only for research purposes and not to identify any individual participant;
2. A commitment to securing the data using appropriate computer technology;
3. A commitment to destroying or returning the data after analyses are completed. All requests are dealt with on a case-by-case basis. Any request should be submitted to the corresponding author who will then review with the Trial Management Group and sponsor. A record of all access to data will be maintained by the Imperial College Archive team.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Imperial College London:

endovenous ablation

Additional relevant MeSH terms:

Varicose Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Varicose Veins; Vascular Diseases; Cardiovascular Diseases