Condition category
Circulatory System
Date applied
02/10/2013
Date assigned
03/10/2013
Last edited
13/07/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
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.

Who can participate?
Men and women, aged 18 or over, with a leg ulcer and varicose veins.

What does the study involve?
Patients will be randomly allocated to one of two treatments: either compression bandaging with treatment of varicose veins after the ulcer has healed (the current best treatment), or compression bandaging and early treatment of the veins. Participants will be followed-up for 1 year via monthly telephone calls with the research nurse and will undergo routine leg ulcer care in community or hospital (or both) settings, in accordance with the local standard. Participants will attend a 6-week clinic visit and complete questionnaires at baseline, 6 weeks, 6 months and 12 months. We will look at the number of ulcers healed in both patient groups and the speed at which the ulcers healed. We will also ask the patients to comment on any changes in their quality of life following treatment. Furthermore, we will look at the costs of the two treatments.

What are the possible benefits and risks of participating?
Both of these treatments are routinely offered to most patients with venous leg ulcers, and therefore the risks of taking part in this study are the same as the risks of having treatment outside of the study. The information gained from the study may help doctors and patients make future decisions as to the best approach (early endovenous treatment compared to standard therapy of compression bandages) to treating venous ulcers in the future. If early treatment of varicose veins improves healing rates in patients with leg ulcers, there will be significant cost savings for the NHS as well as great benefits for the patients.

Where is the study run from?
Imperial College Trials Unit (ICTU) at Imperial College London (UK).

When is the study starting and how long is it expected to run for?
The study started in September 2013 and will run for 4 years.

Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK).

Who is the main contact?
Francine Heatley (trial manager)
f.heatley@imperial.ac.uk

Trial website

www.evrastudy.org

Contact information

Type

Scientific

Primary contact

Prof Alun H Davies

ORCID ID

Contact details

Vascular Surgery
Charing Cross Hospital
London
W6 8RF
United Kingdom
-
a.h.davies@imperial.ac.uk

Type

Public

Additional contact

Ms Francine Heatley

ORCID ID

Contact details

Clinical Trial Manager: EVRA
Imperial College London
Section of Vascular Surgery
Room 3E
4th Floor East Wing
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom
+44 (0)203 311 7371
f.heatley@imperial.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HTA 11/129/197

Study information

Scientific title

A randomized clinical trial to compare early versus delayed endovenous treatment of superficial venous reflux in patients with chronic venous ulceration

Acronym

EVRA

Study hypothesis

What is the clinical and cost effectiveness of early endovenous treatment of superficial venous reflux in addition to standard care compared to standard care alone in patients with chronic venous ulceration?

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/11129197
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0009/82737/PRO-11-129-197.pdf

Ethics approval

South West - Central Bristol research ethics board, 15/08/2013, ref: 13/SW/0199

Study design

Pragmatic multicentre randomized clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Venous disease/leg ulcers

Intervention

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

Participants will be randomized 1:1 to standard compression therapy or early endovenous treatment within 2 weeks in addition to standard therapy.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Time to ulcer healing (from date of randomization to date of healing)

Secondary outcome measures

1. Ulcer Healing Rate: Healing rate will be evaluated in addition to time to ulcer healing to allow comparison with other published studies.
2. Ulcer Free Time: Will be calculated up to 1 year for each study arm. This will allow a very practical and easily understood assessment of the clinical difference between the two arms of the study. This will also allow comparison with other studies that have reported this outcome. In order to facilitate accurate calculation of ulcer free time, clinical follow-up will be continued after ulcer healing up to 1 year after randomization.
3. Quality Of Life (QoL): Disease specific (AVVQ) and generic (EQ5D & SF36) quality of life assessments will be compared at 6 weeks post randomization, 6 months and 12 months. The 6-week questionnaire will be given to the patient at the follow-up appointment, whereas other QoL questionnaires will be sent to the patient. AVVQ is the most widely utilised disease-specific QoL tool in venous disease and has been extensively validated. A score out of 100 points is calculated, with a higher score indicating more severe QoL impairment. Changes in QoL scores will offer a comparison with other studies and, in the standard treatment arm, will allow an assessment of the natural history of venous ulceration treated with compression.
4. Health Economic Assessment: Cost items in hospital and community care will be recorded for each patient. Standard HRG published tariffs will be used to calculate overall costs. A standard tariff will be applied for each bandage change, although additional treatments administered for the treatment of symptoms or complications directly related to venous ulceration will be included. Utilities (QALYs) will be calculated from generic QoL questionnaire and cost-effectiveness will be analysed.
5. Other Markers Of Clinical Success: The Venous Clinical Severity Score (VCSS) will be assessed at 6 weeks. In addition, the incidence of complications related to the endovenous intervention as well as the presence of residual/recurrent varicose veins will also be assessed at 6 weeks.

Overall trial start date

01/09/2013

Overall trial end date

31/08/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Current leg ulceration of greater than 6 weeks, but less than 6 months duration
2. Able to give informed consent to participate in the study after reading the patient information documentation
3. Patient age > 18 years
4. Ankle Brachial Pressure Index (ABPI) greater than or equal to 0.8
5. 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)

Patients who cannot speak/understand English will be eligible for inclusion and informed consent will be obtained
with assistance from translation services as per standard clinical practice. In view of the lack of crosscultural
validation for quality of life tools, only healing outcome data will be collected.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

500

Participant exclusion criteria

1. Presence of deep venous occlusive disease or other conditions precluding superficial venous intervention
2. Patients who are unable to tolerate any multilayer compression bandaging 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 for inclusion. A period of noncompliance with compression bandages will not be considered a protocol violation, but a normal variation within the spectrum of standard therapy.
3. Inability of the patient to receive prompt endovenous intervention by the recruiting centre
4. Pregnancy (female participants of reproductive age will be eligible for inclusion in the study, subject to a negative
pregnancy test prior to randomisation)
5. Leg ulcer of nonvenous aetiology (as assessed by the responsible clinician)
6. If patient is deemed to require skin grafting they cannot be included

Recruitment start date

24/10/2013

Recruitment end date

31/01/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Imperial College Healthcare NHS Trust
-
United Kingdom

Trial participating centre

Cambridge University Hospitals NHS Foundation Trust
-
United Kingdom

Trial participating centre

Worcestershire Acute Hospitals NHS Trust
-
United Kingdom

Trial participating centre

North West London Hospitals NHS Trust
-
United Kingdom

Trial participating centre

Gloucestershire Hospitals NHS Foundation Trust
-
United Kingdom

Trial participating centre

Heart of England NHS Trust
-
United Kingdom

Trial participating centre

University Hospital Birmingham NHS Trust
-
United Kingdom

Trial participating centre

North Cumbria University Hospitals NHS Trust
-
United Kingdom

Trial participating centre

The Dudley Group NHS Trust
-
United Kingdom

Trial participating centre

The Royal Wolverhampton Hospitals NHS Trust
-
United Kingdom

Trial participating centre

York Hospitals NHS Foundation Trust
-
United Kingdom

Trial participating centre

Hull & East Yorkshire Hospitals NHS Trust
-
United Kingdom

Trial participating centre

The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
-
United Kingdom

Trial participating centre

Central Manchester University Hospitals NHS Foundation Trust
-
United Kingdom

Trial participating centre

Frimley Park Hospital NHS Foundation Trust
-
United Kingdom

Trial participating centre

Plymouth Hospitals NHS Trust
-
United Kingdom

Trial participating centre

Bradford Teaching Hospitals NHS Foundation Trust
-
United Kingdom

Trial participating centre

Salisbury NHS Foundation Trust
-
United Kingdom

Trial participating centre

Leeds Teaching Hospitals NHS Trust
-
United Kingdom

Trial participating centre

Sheffield Teaching Hospitals NHS Foundation Trust
-
United Kingdom

Trial participating centre

Taunton and Somerset NHS Foundation Trust
-
United Kingdom

Sponsor information

Organisation

Imperial College London (UK)

Sponsor details

c/o Becky Ward
Research Governance Manager
Joint Research Compliance Office
Imperial College London and Imperial College Healthcare NHS Trust
Room 5L10A
5th Floor
Lab Block
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom
+44 (0)203 311 0205
becky.ward@imperial.ac.uk

Sponsor type

University/education

Website

http://www3.imperial.ac.uk

Funders

Funder type

Government

Funder name

NIHR Health Technology Assessment Programme - HTA (UK) 11/129/197

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes