NCT03286140: EVRA

Early Venous Reflux Ablation Ulcer Trial

Completed NA Results posted Last updated 20 May 2024

What this trial tests

NA trial testing Early endovenous ablation in Venous Leg Ulcer in 450 participants. Completed in 31 March 2019.

Timeline

1 September 2013

Primary endpoint
31 March 2019

31 March 2019

Quick facts

Lead sponsor	Imperial College London
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	450
Start date	1 September 2013
Primary completion	31 March 2019
Estimated completion	31 March 2019
Sites	1 location across United Kingdom

Drugs / interventions tested

• Early endovenous ablation
• Delayed endovenous intervention

Conditions studied

• Venous Leg Ulcer — all drugs for Venous Leg Ulcer →

Sponsor

Imperial College London

Who can join

18 and older, any sex, with Venous Leg Ulcer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to Ulcer Healing From Date of Randomisation to Date of Healing up to 365 Days Primary · 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.

Group	Value	95% CI
Standard Therapy Arm	82	69 – 92
Early Arm	56	49 – 66

Percentage of Participants With Ulcer Healing Secondary · 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

Group	Value	95% CI
Standard Therapy Arm	76.3	70.5 – 81.5
Early Arm	85.6	80.6 – 89.8

Ulcer Recurrence / Ulcer Free Time Secondary · 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.

Group	Value	95% CI
Standard Therapy Arm	32
Early Arm	24

Quality Of Life Questionnaire up to 365 Days Secondary · 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).

6-week AVVQ

Group	Value	95% CI
Standard Therapy Arm	41.2	± 9.3
Early Arm	39.4	± 10.2

6-month AVVQ

Group	Value	95% CI
Standard Therapy Arm	39.5	± 10.3
Early Arm	34.6	± 9.4

12-month AVVQ

Group	Value	95% CI
Standard Therapy Arm	34.3	± 10.4
Early Arm	32.4	± 8.3

Generic (SF-36) Quality of Life Assessment Secondary · 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

6-week SF-36

Group	Value	95% CI
Standard Therapy Arm	45.6	± 9.2
Early Arm	45.7	± 9.1

6-month SF-36

Group	Value	95% CI
Standard Therapy Arm	44.5	± 10.1
Early Arm	44.9	± 9.8

12-month SF-36

Group	Value	95% CI
Standard Therapy Arm	45.1	± 10
Early Arm	45.3	± 10

EuroQol-5 Dimensions (EQ-5D) Secondary · 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.

6-week EQ-5D

Group	Value	95% CI
Standard Therapy Arm	71.1	± 18.7
Early Arm	72.7	± 18.6

6-month EQ-5D

Group	Value	95% CI
Standard Therapy Arm	71.4	± 19.6
Early Arm	74.1	± 15.8

12-month EQ-5D

Group	Value	95% CI
Standard Therapy Arm	73.7	± 17.4
Early Arm	74.8	± 16.9

Health Economic Assessment Secondary · 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

Group	Value	95% CI
Standard Therapy Arm	2516	± 3242
Early Arm	2514	± 2770

Clinical Success - Presence of Residual / Recurrent Reflux in the Veins Secondary · 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)

Group	Value	95% CI
Standard Therapy Arm	1
Early Arm	1
Standard Therapy Arm	225
Early Arm	224

Clinical Success - VCSS Secondary · 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).

Group	Value	95% CI
Standard Therapy Arm	12.6	± 4.4
Early Arm	10.5	± 4.7

Clinical Success - Complications Secondary · up to 12 months

Number of complications related to the endovenous intervention

Group	Value	95% CI
Standard Therapy Arm	24
Early Arm	28

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs collected over 12-months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Standard Therapy Arm

Serious: 51/226 (23%)

Deaths: 4/226

Early Arm

Serious: 40/224 (18%)

Deaths: 3/224

Serious adverse events (2 terms)

Reaction	System	Standard Therapy Arm	Early Arm
Hospitalisation Required	General disorders	—	—
Other	General disorders	—	—

Other adverse events (1 terms — click to expand)

Reaction	System	Standard Therapy Arm	Early Arm
New ulcer	Vascular disorders	—	—

Most-reported serious reactions: Hospitalisation Required, Other.

Data from ClinicalTrials.gov NCT03286140 adverse events section.

Sponsor's own description

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

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.