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| Name | Class |
|---|---|
| University of Birmingham | OTHER |
| Universidad de Granada | OTHER |
| University of Manchester | OTHER |
| University of Warwick |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard therapy arm | Active Comparator | Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) |
|
| Early arm | Experimental | Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Early endovenous ablation | Procedure |
| ||
| Delayed endovenous intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Ulcer Healing 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. | time from date of randomisation to date of healing up to 365 days |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Ulcer Healing | Healing rate will be reported at 24 weeks using the percentage of participants with a healed ulcer | 24 weeks & time to ulcer healing up to 365 days |
| Ulcer Recurrence / Ulcer Free Time |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gerard Stansby | Newcastle University | Study Chair |
| Julie Brittenden | University of Glasgow | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Imperial College London | London | W68RF | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32965493 | Result | 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. | |
| 31140402 |
| Label | URL |
|---|---|
| Trial website | View source |
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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:
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| ID | Title | Description |
|---|---|---|
| FG000 | Standard Therapy Arm | Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention |
| FG001 | Early Arm | Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Standard Therapy Arm | Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention |
| BG001 | Early Arm |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time to Ulcer Healing 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. | 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. | Posted | Median | 95% Confidence Interval | days | time from date of randomisation to date of healing up to 365 days |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard Therapy Arm | Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed) Delayed endovenous intervention |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalisation Required | General disorders | (MedDRA | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| New ulcer | Vascular disorders | MedDRA® version 20 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Alun Davies | Imperial College London | +44 (0)20 3311 7309 | a.h.davies@imperial.ac.uk |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 6, 2017 | Apr 12, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 26, 2017 | Apr 12, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D014647 | Varicose Ulcer |
| ID | Term |
|---|---|
| D014648 | Varicose Veins |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D007871 | Leg Ulcer |
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| OTHER |
The EVRA ulcer trial is a pragmatic; multicentre randomised clinical trial with participants randomised1:1 to either:
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Blinded assessment of ulcer healing photos
| Procedure |
|
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.
| Up to 12 months (and with the extension, up to 5 years (median approximately 3.7 years)) |
| Quality Of Life Questionnaire up to 365 Days | 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 weeks post randomisation, 6 months, 12 months |
| Generic (SF-36) Quality of Life Assessment | 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. | 6 weeks post randomisation, 6 months, 12 months |
| EuroQol-5 Dimensions (EQ-5D) | 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 weeks post randomisation, 6 months, 12 months |
| Health Economic Assessment | 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 | Baseline, 6 weeks, 6 months, 12 months |
| Clinical Success - Presence of Residual / Recurrent Reflux in the Veins | 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). | at 6 weeks |
| Clinical Success - VCSS | 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). | at 6 weeks |
| Clinical Success - Complications | Number of complications related to the endovenous intervention | up to 12 months |
| Result |
| 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. |
| Failure to comply |
|
Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy
Early endovenous ablation
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Weight (kg) | Mean | Standard Deviation | kg |
|
| Height (cm) | Mean | Standard Deviation | cm |
|
| BMI (kg/m2 ) | Mean | Standard Deviation | kg/m2 |
|
| Smoking | Count of Participants | Participants |
|
| Previous ulcer | Number | participants |
|
| OG001 |
| Early Arm |
Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation |
|
|
| Secondary | Percentage of Participants With Ulcer Healing | Healing rate will be reported at 24 weeks using the percentage of participants with a healed ulcer | Posted | Number | 95% Confidence Interval | percentage of participants | 24 weeks & time to ulcer healing up to 365 days |
|
|
|
| Secondary | Ulcer Recurrence / Ulcer Free Time | 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. | All participants with a healed ulcer within 1 year post-randomisation | Posted | Count of Participants | Participants | Up to 12 months (and with the extension, up to 5 years (median approximately 3.7 years)) |
|
|
|
| Secondary | Quality Of Life Questionnaire up to 365 Days | 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). | Missing data at follow-up | Posted | Mean | Standard Deviation | score on a scale | 6 weeks post randomisation, 6 months, 12 months |
|
|
|
| Secondary | Generic (SF-36) Quality of Life Assessment | 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. | SF-36 general health score | Posted | Mean | Standard Deviation | score on a scale | 6 weeks post randomisation, 6 months, 12 months |
|
|
|
| Secondary | EuroQol-5 Dimensions (EQ-5D) | 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. | 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 | Posted | Mean | Standard Deviation | score on a scale | 6 weeks post randomisation, 6 months, 12 months |
|
|
|
| Secondary | Health Economic Assessment | 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 | As randomised, less early withdrawals | Posted | Mean | Standard Deviation | Costs (pounds) at one year | Baseline, 6 weeks, 6 months, 12 months |
|
|
|
| Secondary | Clinical Success - Presence of Residual / Recurrent Reflux in the Veins | 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). | CEAP classification | Posted | Count of Participants | Participants | at 6 weeks |
|
|
|
| Secondary | Clinical Success - VCSS | 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). | Posted | Mean | Standard Deviation | score on a scale | at 6 weeks |
|
|
|
| Secondary | Clinical Success - Complications | Number of complications related to the endovenous intervention | Posted | Number | participants | up to 12 months |
|
|
|
| 4 |
| 226 |
| 51 |
| 226 |
| 83 |
| 226 |
| EG001 | Early Arm | Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy Early endovenous ablation | 3 | 224 | 40 | 224 | 67 | 224 |
| Other | General disorders | MedDRA® version 20 | Non-systematic Assessment |
|
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| D012883 |
| Skin Ulcer |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| 6-month AVVQ |
|
|
| 12-month AVVQ |
|
|
| 6-month SF-36 |
|
|
| 12-month SF-36 |
|
|
| 6-month EQ-5D |
|
|
| 12-month EQ-5D |
|
|