Clinical trial NCT03286140: Early Venous Reflux Ablation Ulcer Trial
Official title: A Randomised Clinical Trial to Compare Early Versus Delayed Endovenous Treatment of Superficial Venous Reflux in Patients With Chronic Venous Ulceration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Venous Leg Ulcer
Keywords: endovenous ablation
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: University of Birmingham
name: Universidad de Granada
name: University of Manchester
name: University of Warwick
First posted: 2017-09-18
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Time to Ulcer Healing From Date of Randomisation to Date of Healing up to 365 Days
timeFrame: time from date of randomisation to date of healing up to 365 days
Secondary outcomes:
measure: Percentage of Participants With Ulcer Healing
timeFrame: 24 weeks & time to ulcer healing up to 365 days
measure: Ulcer Recurrence / Ulcer Free Time
timeFrame: Up to 12 months (and with the extension, up to 5 years (median approximately 3.7 years))
measure: Quality Of Life Questionnaire up to 365 Days
timeFrame: 6 weeks post randomisation, 6 months, 12 months
measure: Generic (SF-36) Quality of Life Assessment
timeFrame: 6 weeks post randomisation, 6 months, 12 months
measure: EuroQol-5 Dimensions (EQ-5D)
timeFrame: 6 weeks post randomisation, 6 months, 12 months
measure: Health Economic Assessment
timeFrame: Baseline, 6 weeks, 6 months, 12 months
measure: Clinical Success - Presence of Residual / Recurrent Reflux in the Veins
timeFrame: at 6 weeks
measure: Clinical Success - VCSS
timeFrame: at 6 weeks
measure: Clinical Success - Complications
timeFrame: up to 12 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College London
Study officials:
affiliation: Newcastle University
name: Gerard Stansby
role: STUDY_CHAIR
affiliation: University of Glasgow
name: Julie Brittenden
role: STUDY_CHAIR
References:
citation: Gohel MS, Mora MSc J, Szigeti M, Epstein DM, Heatley F, Bradbury A, Bulbulia R, Cullum N, Nyamekye I, Poskitt KR, Renton S, Warwick J, Davies AH; Early Venous Reflux Ablation Trial Group. Long-term Clinical and Cost-effectiveness of Early Endovenous Ablation in Venous Ulceration: A Randomized Clinical Trial. JAMA Surg. 2020 Dec 1;155(12):1113-1121. doi: 10.1001/jamasurg.2020.3845.
citation: Gohel MS, Heatley F, Liu X, Bradbury A, Bulbulia R, Cullum N, Epstein DM, Nyamekye I, Poskitt KR, Renton S, Warwick J, Davies AH. Early versus deferred endovenous ablation of superficial venous reflux in patients with venous ulceration: the EVRA RCT. Health Technol Assess. 2019 May;23(24):1-96. doi: 10.3310/hta23240.