<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03286140</url>
  </required_header>
  <id_info>
    <org_study_id>13HH0722</org_study_id>
    <nct_id>NCT03286140</nct_id>
  </id_info>
  <brief_title>Early Venous Reflux Ablation Ulcer Trial</brief_title>
  <acronym>EVRA</acronym>
  <official_title>A Randomised Clinical Trial to Compare Early Versus Delayed Endovenous Treatment of Superficial Venous Reflux in Patients With Chronic Venous Ulceration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Birmingham</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Universidad de Granada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Manchester</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Warwick</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Imperial College London</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The EVRA study evaluates the effects of early endovenous ablation on ulcer healing in&#xD;
      patients with chronic venous ulceration. Half the patients are randomised to receive early&#xD;
      endovenous ablation (within 2 weeks) and half to standard care&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A large number of patients (around 1% of the adult population) suffer from an ulcer (break in&#xD;
      the skin surface) near the ankle. In most people, such an injury should heal up within a week&#xD;
      or two. However, when there is an underlying problem with the skin, ulcers do not heal and&#xD;
      may result in longstanding (chronic), painful, smelly and embarrassing wounds. The ulcers are&#xD;
      often due to varicose veins in the legs, which can cause skin breakdown and ulcer formation.&#xD;
      To get the ulcer to heal, the current best treatment is to wear a tight compression bandage&#xD;
      with multiple layers, with which about 60% of these ulcers will heal within 24 weeks. There&#xD;
      is evidence that treatment of the varicose veins by surgery will prevent the ulcer from&#xD;
      returning after it has healed. Recent studies have suggested that newer techniques of&#xD;
      treating varicose veins, such as injecting a medicine into the varicose vein (sclerotherapy)&#xD;
      or treating the vein with heat ablation to seal it (using laser or radiofrequency), in an&#xD;
      outpatient setting may help the ulcers to heal more quickly and (like surgery) reduce the&#xD;
      chance of the ulcer coming back. These techniques can be carried out in the outpatient&#xD;
      setting and are much better tolerated by patients in comparison to surgery. The aim of this&#xD;
      study is to see whether early treatment of varicose veins using sclerotherapy or heat&#xD;
      ablation helps with healing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2013</start_date>
  <completion_date type="Actual">March 31, 2019</completion_date>
  <primary_completion_date type="Actual">March 31, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>The EVRA ulcer trial is a pragmatic; multicentre randomised clinical trial with participants randomised1:1 to either:&#xD;
'Standard' therapy consisting of multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed)&#xD;
Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard therapy</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Blinded assessment of ulcer healing photos</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Time to ulcer healing</measure>
    <time_frame>time from date of randomisation to date of healing within the 12 month study period</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ulcer Healing Rate</measure>
    <time_frame>24 weeks &amp; time to ulcer healing within the 12 month study period</time_frame>
    <description>Healing rate will be reported at 24 weeks in addition to time to ulcer healing to allow comparison with other published studies</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ulcer recurrence / Ulcer Free Time</measure>
    <time_frame>Up to 12 months (and with the extension, up to 5 years (median approximately 3.7 years))</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality Of Life Questionnaire</measure>
    <time_frame>6 weeks post randomisation, 6 months, 12 months and at one time point between October 2018 and March 2019</time_frame>
    <description>Disease specific (AVVQ) quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality Of Life Questionnaire</measure>
    <time_frame>6 weeks post randomisation, 6 months, 12 months and at one time point between October 2018 and March 2019</time_frame>
    <description>Generic (SF36) quality of life assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality Of Life Questionnaire</measure>
    <time_frame>6 weeks post randomisation, 6 months, 12 months and at one time point between October 2018 and March 2019</time_frame>
    <description>Generic (EQ5D )quality of life assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Economic Assessment</measure>
    <time_frame>Baseline, 6 weeks, 6 months, 12 months</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Success - Presence of residual / recurrent varicose veins</measure>
    <time_frame>at 6 weeks</time_frame>
    <description>The presence of residual / recurrent varicose veins remaining on the venous duplex</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Success - VCSS</measure>
    <time_frame>at 6 weeks</time_frame>
    <description>The Venous Clinical Severity Score (VCSS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Success - Complications</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Incidence of complications related to the endovenous intervention</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">450</enrollment>
  <condition>Venous Leg Ulcer</condition>
  <arm_group>
    <arm_group_label>Standard therapy arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Early arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Early endovenous ablation</intervention_name>
    <arm_group_label>Early arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Delayed endovenous intervention</intervention_name>
    <arm_group_label>Standard therapy arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Current leg ulceration of greater than 6 weeks, but less than 6 months duration&#xD;
&#xD;
          -  Able to give informed consent to participate in the study after reading the patient&#xD;
             information documentation&#xD;
&#xD;
          -  Patient age &gt; 18 years&#xD;
&#xD;
          -  Ankle Brachial Pressure Index (ABPI) ≥ 0.8&#xD;
&#xD;
          -  Superficial venous disease on colour duplex assessment deemed to be significant enough&#xD;
             to warrant ablation by the treating clinician (either primary or recurrent venous&#xD;
             reflux)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of deep venous occlusive disease or other conditions precluding superficial&#xD;
             venous intervention (at the discretion of local research team)&#xD;
&#xD;
          -  Patients who are unable to tolerate any multilayer compression bandaging / stockings&#xD;
             will be excluded. However, concordance with compression therapy can be variable for&#xD;
             patients at different times. Patients who are generally compliant with compression,&#xD;
             but unable to tolerate the bandages for short periods will still be eligible to&#xD;
             inclusion. A period of non-compliance with compression bandages will not be considered&#xD;
             a protocol violation, but a normal variation within the spectrum of 'standard&#xD;
             therapy'.&#xD;
&#xD;
          -  Inability of the patient to receive prompt endovenous intervention by recruiting&#xD;
             centre&#xD;
&#xD;
          -  Pregnancy (female participants of reproductive age will be eligible for inclusion in&#xD;
             the study, subject to a negative pregnancy test prior to randomisation)&#xD;
&#xD;
          -  Leg ulcer of non-venous aetiology (as assessed by responsible clinician)&#xD;
&#xD;
          -  Patient deemed to require skin grafting&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gerard Stansby</last_name>
    <role>Study Chair</role>
    <affiliation>Newcastle University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Julie Brittenden</last_name>
    <role>Study Chair</role>
    <affiliation>University of Glasgow</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Imperial College London</name>
      <address>
        <city>London</city>
        <zip>W68RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <last_update_submitted>July 10, 2019</last_update_submitted>
  <last_update_submitted_qc>July 10, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>endovenous ablation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Varicose Ulcer</mesh_term>
    <mesh_term>Leg Ulcer</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>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.&#xD;
Data and associated documentation will be available to users only under a data-sharing agreement that provides for the following:&#xD;
A commitment to using the data only for research purposes and not to identify any individual participant;&#xD;
A commitment to securing the data using appropriate computer technology;&#xD;
A commitment to destroying or returning the data after analyses are completed. All requests are dealt with on a case-by-case basis. Any request should be submitted to the corresponding author who will then review with the Trial Management Group and sponsor. A record of all access to data will be maintained by the Imperial College Archive team.</ipd_description>
  </patient_data>
  <pending_results>
    <submitted>April 12, 2022</submitted>
    <returned>January 9, 2023</returned>
    <submitted>February 21, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03286140
org study id: 13HH0722
nct id: NCT03286140
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The EVRA ulcer trial is a pragmatic; multicentre randomised clinical trial with participants randomised1:1 to either:
'Standard' therapy consisting of multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed)
Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard therapy
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Blinded assessment of ulcer healing photos
measure: Time to ulcer healing
time frame: time from date of randomisation to date of healing within the 12 month study period
description: 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.
measure: Ulcer Healing Rate
time frame: 24 weeks & time to ulcer healing within the 12 month study period
description: Healing rate will be reported at 24 weeks in addition to time to ulcer healing to allow comparison with other published studies
measure: Ulcer recurrence / Ulcer Free Time
time frame: Up to 12 months (and with the extension, up to 5 years (median approximately 3.7 years))
description: 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.
measure: Quality Of Life Questionnaire
time frame: 6 weeks post randomisation, 6 months, 12 months and at one time point between October 2018 and March 2019
description: Disease specific (AVVQ) quality of life
measure: Quality Of Life Questionnaire
time frame: 6 weeks post randomisation, 6 months, 12 months and at one time point between October 2018 and March 2019
description: Generic (SF36) quality of life assessment
measure: Quality Of Life Questionnaire
time frame: 6 weeks post randomisation, 6 months, 12 months and at one time point between October 2018 and March 2019
description: Generic (EQ5D )quality of life assessment
measure: Health Economic Assessment
time frame: Baseline, 6 weeks, 6 months, 12 months
description: 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
measure: Clinical Success - Presence of residual / recurrent varicose veins
time frame: at 6 weeks
description: The presence of residual / recurrent varicose veins remaining on the venous duplex
measure: Clinical Success - VCSS
time frame: at 6 weeks
description: The Venous Clinical Severity Score (VCSS)
measure: Clinical Success - Complications
time frame: up to 12 months
description: Incidence of complications related to the endovenous intervention
arm group label: Standard therapy arm
arm group type: Active Comparator
description: Multilayer elastic compression bandaging/ stockings with deferred treatment of superficial reflux (usually once the ulcer has healed)
arm group label: Early arm
arm group type: Experimental
description: Early endovenous treatment of superficial venous reflux(within 2 weeks) in addition to standard compression therapy
intervention type: Procedure
intervention name: Early endovenous ablation
arm group label: Early arm
intervention type: Procedure
intervention name: Delayed endovenous intervention
arm group label: Standard therapy arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gerard Stansby
role: Study Chair
affiliation: Newcastle University
last name: Julie Brittenden
role: Study Chair
affiliation: University of Glasgow
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Varicose Ulcer
mesh term: Leg Ulcer
sharing ipd: Undecided
ipd description: 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:
A commitment to using the data only for research purposes and not to identify any individual participant;
A commitment to securing the data using appropriate computer technology;
A commitment to destroying or returning the data after analyses are completed. All requests are dealt with on a case-by-case basis. Any request should be submitted to the corresponding author who will then review with the Trial Management Group and sponsor. A record of all access to data will be maintained by the Imperial College Archive team.
submitted: April 12, 2022
returned: January 9, 2023
submitted: February 21, 2023