Trial Outcomes & Findings for Early Venous Reflux Ablation Ulcer Trial (NCT NCT03286140)

NCT ID: NCT03286140

Last Updated: 2024-05-20

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 450 participants
• Primary outcome timeframe: time from date of randomisation to date of healing up to 365 days
• Results posted on: 2024-05-20

Participant Flow

Participant milestones

Measure	Standard Therapy Arm Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
Overall Study STARTED	226	224
Overall Study 6-week Follow-up	224	223
Overall Study 6-month Follow-up	215	213
Overall Study 12-month Follow-up	203	204
Overall Study COMPLETED	211	208
Overall Study NOT COMPLETED	15	16

Reasons for withdrawal

Measure	Standard Therapy Arm Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
Overall Study Withdrawal by Subject	10	5
Overall Study Lost to Follow-up	5	10
Overall Study Failure to comply	0	1

Baseline Characteristics

Early Venous Reflux Ablation Ulcer Trial

Baseline characteristics by cohort

Measure	Standard Therapy Arm n=226 Participants Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm n=224 Participants Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation	Total n=450 Participants Total of all reporting groups
Age, Continuous	68.9 years STANDARD_DEVIATION 14 • n=5 Participants	67 years STANDARD_DEVIATION 15.5 • n=7 Participants	68 years STANDARD_DEVIATION 14.8 • n=5 Participants
Sex: Female, Male Female	106 Participants n=5 Participants	97 Participants n=7 Participants	203 Participants n=5 Participants
Sex: Female, Male Male	120 Participants n=5 Participants	127 Participants n=7 Participants	247 Participants n=5 Participants
Race/Ethnicity, Customized White	208 Participants n=5 Participants	206 Participants n=7 Participants	414 Participants n=5 Participants
Race/Ethnicity, Customized Mixed	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Race/Ethnicity, Customized Black	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Weight (kg)	88.8 kg STANDARD_DEVIATION 24.1 • n=5 Participants	89.5 kg STANDARD_DEVIATION 25.6 • n=7 Participants	89.1 kg STANDARD_DEVIATION 24.9 • n=5 Participants
Height (cm)	170.5 cm STANDARD_DEVIATION 10.8 • n=5 Participants	171.9 cm STANDARD_DEVIATION 11.1 • n=7 Participants	171.2 cm STANDARD_DEVIATION 11.0 • n=5 Participants
BMI (kg/m2 )	30.4 kg/m2 STANDARD_DEVIATION 7.4 • n=5 Participants	30.1 kg/m2 STANDARD_DEVIATION 7.8 • n=7 Participants	30.3 kg/m2 STANDARD_DEVIATION 7.6 • n=5 Participants
Smoking Current	19 Participants n=5 Participants	23 Participants n=7 Participants	42 Participants n=5 Participants
Smoking Former	101 Participants n=5 Participants	86 Participants n=7 Participants	187 Participants n=5 Participants
Smoking Never	106 Participants n=5 Participants	115 Participants n=7 Participants	221 Participants n=5 Participants
Previous ulcer Yes	117 participants n=5 Participants	118 participants n=7 Participants	235 participants n=5 Participants
Previous ulcer No	108 participants n=5 Participants	106 participants n=7 Participants	214 participants n=5 Participants
Previous ulcer Not completed	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: time from date of randomisation to date of healing up to 365 days

Population: 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.

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.

Outcome measures

Measure	Standard Therapy Arm n=226 Participants Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm n=224 Participants Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
Time to Ulcer Healing From Date of Randomisation to Date of Healing up to 365 Days	82 days Interval 69.0 to 92.0	56 days Interval 49.0 to 66.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Standard Therapy Arm n=226 Participants Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm n=224 Participants Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
Percentage of Participants With Ulcer Healing	76.3 percentage of participants Interval 70.5 to 81.5	85.6 percentage of participants Interval 80.6 to 89.8

SECONDARY outcome

Timeframe: Up to 12 months (and with the extension, up to 5 years (median approximately 3.7 years))

Population: All participants with a healed ulcer within 1 year post-randomisation

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.

Outcome measures

Measure	Standard Therapy Arm n=194 Participants Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm n=210 Participants Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
Ulcer Recurrence / Ulcer Free Time	32 Participants	24 Participants

SECONDARY outcome

Timeframe: 6 weeks post randomisation, 6 months, 12 months

Population: Missing data at follow-up

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).

Outcome measures

Measure	Standard Therapy Arm n=170 Participants Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm n=176 Participants Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
Quality Of Life Questionnaire up to 365 Days 6-week AVVQ	41.2 score on a scale Standard Deviation 9.3	39.4 score on a scale Standard Deviation 10.2
Quality Of Life Questionnaire up to 365 Days 6-month AVVQ	39.5 score on a scale Standard Deviation 10.3	34.6 score on a scale Standard Deviation 9.4
Quality Of Life Questionnaire up to 365 Days 12-month AVVQ	34.3 score on a scale Standard Deviation 10.4	32.4 score on a scale Standard Deviation 8.3

SECONDARY outcome

Timeframe: 6 weeks post randomisation, 6 months, 12 months

Population: SF-36 general health score

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 eight separate domain scores. Each score is measured on a scale of 0 to 100 (worst to best). Scores represent the percentage of total possible score achieved.

Outcome measures

Measure	Standard Therapy Arm n=207 Participants Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm n=212 Participants Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
Generic (SF-36) Quality of Life Assessment 6-week SF-36	45.6 score on a scale Standard Deviation 9.2	45.7 score on a scale Standard Deviation 9.1
Generic (SF-36) Quality of Life Assessment 6-month SF-36	44.5 score on a scale Standard Deviation 10.1	44.9 score on a scale Standard Deviation 9.8
Generic (SF-36) Quality of Life Assessment 12-month SF-36	45.1 score on a scale Standard Deviation 10	45.3 score on a scale Standard Deviation 10

SECONDARY outcome

Timeframe: 6 weeks post randomisation, 6 months, 12 months

Population: EQ-5D health score Scores on the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L) health scale (a visual-analogue scale) range from 0 to 100, with higher scores indicating better health. Score on the EQ-5D-5L health index range from 0 to 1, with higher scores indicating better health. The EQ-5D-5L health index was calculated with the value set for England

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.

Outcome measures

Measure	Standard Therapy Arm n=205 Participants Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm n=212 Participants Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
EuroQol-5 Dimensions (EQ-5D) 6-week EQ-5D	71.1 score on a scale Standard Deviation 18.7	72.7 score on a scale Standard Deviation 18.6
EuroQol-5 Dimensions (EQ-5D) 6-month EQ-5D	71.4 score on a scale Standard Deviation 19.6	74.1 score on a scale Standard Deviation 15.8
EuroQol-5 Dimensions (EQ-5D) 12-month EQ-5D	73.7 score on a scale Standard Deviation 17.4	74.8 score on a scale Standard Deviation 16.9

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 6 months, 12 months

Population: As randomised, less early withdrawals

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

Outcome measures

Measure	Standard Therapy Arm n=211 Participants Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm n=208 Participants Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
Health Economic Assessment	2516 Costs (pounds) at one year Standard Deviation 3242	2514 Costs (pounds) at one year Standard Deviation 2770

SECONDARY outcome

Timeframe: at 6 weeks

Population: CEAP classification

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).

Outcome measures

Measure	Standard Therapy Arm n=226 Participants Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm n=225 Participants Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
Clinical Success - Presence of Residual / Recurrent Reflux in the Veins CEAP 5	1 Participants	1 Participants
Clinical Success - Presence of Residual / Recurrent Reflux in the Veins CEAP 6	225 Participants	224 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Standard Therapy Arm n=226 Participants Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm n=224 Participants Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
Clinical Success - VCSS	12.6 score on a scale Standard Deviation 4.4	10.5 score on a scale Standard Deviation 4.7

SECONDARY outcome

Timeframe: up to 12 months

Number of complications related to the endovenous intervention

Outcome measures

Measure	Standard Therapy Arm n=226 Participants Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm n=224 Participants Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
Clinical Success - Complications	24 participants	28 participants

Adverse Events

Standard Therapy Arm

Serious events: 51 serious events

Other events: 83 other events

Deaths: 4 deaths

Early Arm

Serious events: 40 serious events

Other events: 67 other events

Deaths: 3 deaths

Serious adverse events

Measure	Standard Therapy Arm n=226 participants at risk Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm n=224 participants at risk Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
General disorders Hospitalisation Required	22.1% 50/226 • AEs collected over 12-months The research nurses collected data regarding the occurrence of all SAEs via the monthly telephone calls, clinic or surgery notes, and hospital admission records. These were reported to the ICTU via the web-based data capture system within 24 hours of the nurses becoming aware of the event and reviewed by the chief investigator.	17.0% 38/224 • AEs collected over 12-months The research nurses collected data regarding the occurrence of all SAEs via the monthly telephone calls, clinic or surgery notes, and hospital admission records. These were reported to the ICTU via the web-based data capture system within 24 hours of the nurses becoming aware of the event and reviewed by the chief investigator.
General disorders Other	0.44% 1/226 • AEs collected over 12-months The research nurses collected data regarding the occurrence of all SAEs via the monthly telephone calls, clinic or surgery notes, and hospital admission records. These were reported to the ICTU via the web-based data capture system within 24 hours of the nurses becoming aware of the event and reviewed by the chief investigator.	0.89% 2/224 • AEs collected over 12-months The research nurses collected data regarding the occurrence of all SAEs via the monthly telephone calls, clinic or surgery notes, and hospital admission records. These were reported to the ICTU via the web-based data capture system within 24 hours of the nurses becoming aware of the event and reviewed by the chief investigator.

Other adverse events

Measure	Standard Therapy Arm n=226 participants at risk Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention	Early Arm n=224 participants at risk Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation
Vascular disorders New ulcer	36.7% 83/226 • AEs collected over 12-months The research nurses collected data regarding the occurrence of all SAEs via the monthly telephone calls, clinic or surgery notes, and hospital admission records. These were reported to the ICTU via the web-based data capture system within 24 hours of the nurses becoming aware of the event and reviewed by the chief investigator.	29.9% 67/224 • AEs collected over 12-months The research nurses collected data regarding the occurrence of all SAEs via the monthly telephone calls, clinic or surgery notes, and hospital admission records. These were reported to the ICTU via the web-based data capture system within 24 hours of the nurses becoming aware of the event and reviewed by the chief investigator.

Additional Information

Professor Alun Davies

Imperial College London

Phone: +44 (0)20 3311 7309

Email: a.h.davies@imperial.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place