<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/NCT01671748</url>
  </required_header>
  <id_info>
    <org_study_id>12-SUR-5323</org_study_id>
    <nct_id>NCT01671748</nct_id>
  </id_info>
  <brief_title>MIST Ultrasound Therapy Compared to United Kingdom Standard Care for the Treatment of Non-healing Venous Leg Ulcers</brief_title>
  <official_title>Pragmatic Randomised Controlled Trial of MIST Ultrasound Therapy Compared to UK Standard Care for the Treatment of Non-healing Venous Leg Ulcers.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cardiff and Vale University Health Board</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celleration, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Cardiff and Vale University Health Board</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Chronic venous leg ulcers (VLUs) impact negatively on patients' quality of life. Standard&#xD;
      treatment in the UK for patients with VLUs is compression bandaging or stockings. The MIST&#xD;
      ultrasound system is a noncontact device which delivers low frequency ultrasound through a&#xD;
      gentle saline mist directed at a patient's wound. This study aims to determine whether the&#xD;
      use of the MIST device used in combination with standard treatments can improve healing of&#xD;
      VLUs compared to UK standard practice. This will be assessed by measuring any reduction in&#xD;
      wound size in the two groups after receiving 8 weeks of either Standard Care once a week or&#xD;
      MIST combined with Standard Care three times a week.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Venous leg ulcers (VLUs) are wounds which are often chronic and difficult to heal. VLUs&#xD;
      affect between 1 and 3.2 people per 1000; they cause pain, reduced mobility and impact&#xD;
      negatively on patients' quality of life (QoL). Standard treatment for patients with VLUs is&#xD;
      the application of strong, sustained compression with bandages or stockings. This&#xD;
      pragmatically-designed study aims to determine whether the use of a device called MIST used&#xD;
      in combination with standard treatments can improve healing of VLUs compared to UK standard&#xD;
      practice. It will also show whether the MIST regimen improves participants' QoL and reduces&#xD;
      the incidence of infection.&#xD;
&#xD;
      The MIST ultrasound system is a non-contact device which delivers low-frequency ultrasound&#xD;
      through a gentle saline mist directed at a patient's wound. Patients (over 18 years old) will&#xD;
      be invited to take part in this study if they have had a VLU for 6 weeks or more, which&#xD;
      measures between 5 and 100 cm^2, and is not infected. Participants with diabetes must show&#xD;
      good blood glucose control, and those with underlying chronic disorders which may affect&#xD;
      wound healing will be excluded.&#xD;
&#xD;
      All study participants will receive four weeks of standard treatment once a week at a single&#xD;
      clinic at the Wound Healing Research Unit (WHRU), University Hospital of Wales. Patients&#xD;
      whose wounds reduce by more than 40% during this time will be withdrawn from the study.&#xD;
      Remaining patients will be randomly allocated to either the active group or the control group&#xD;
      to receive a further eight weeks of treatment. Participants in the active group will receive&#xD;
      treatment with the MIST device three times a week, as well as standard care (change of&#xD;
      compression bandage and dressings) three times a week. The control group will receive UK&#xD;
      standard care (which is dressing and compression bandage change at least once a week). The&#xD;
      participants' ulcers will be measured and photographed once a week, and the wound&#xD;
      characteristics will be assessed. Changes in participants' health related QoL will be&#xD;
      assessed using a questionnaire at the beginning and end of the trial. Wound recurrence rates&#xD;
      90 days after the end of the treatment will be assessed by telephoning patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage Change in Wound Area</measure>
    <time_frame>Week 5 to 13</time_frame>
    <description>Wound area is measured weekly using a digital wound imaging device. The wound boundary is digitally traced by a blinded assessor. Percentage and actual change in wound area between start of treatment (week 5) and end of treatment (week 13) is evaluated.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Actual Change in Wound Area</measure>
    <time_frame>Week 5 to 13</time_frame>
    <description>Wound area is measured weekly using a digital wound imaging device. The wound boundary is digitally traced by a blinded assessor. Percentage and actual change in wound area between start of treatment (week 5) and end of treatment (week 13) is evaluated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Overall Health Related Quality of Life (HRQoL) From Week 1 (Start) and Week 13 (Exit)</measure>
    <time_frame>Week 1 (start) and week 13 (exit)</time_frame>
    <description>On the first and final visit participants were invited to complete a Cardiff Wound Impact Schedule (CWIS) a validated questionnaire designed to measure the impact of chronic wounds on patient health-related quality of life (HRQoL). The overall HRQoL question asks patients to rate their overall quality of life over the past week by circling a number between 0 and 10. Low scores indicate poor quality of life, and high score indicate good quality of life. Change in HRQoL was calculated by subtracting week 1 values from week 13 values.&#xD;
CWIS has been validated in the following paper: Price and Harding (2004) The Cardiff Wound Impact Schedule: the development of a condition specific questionnaire to assess health-related quality of life in patients with chronic wounds. International Wound Journal 1(1):10-17</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Ulcer Pain Between Week 5 (Randomisation) and Week 13 (Exit)</measure>
    <time_frame>Weeks 5 to 13</time_frame>
    <description>Pain was scored by each patient on a visual analogue score (VAS) from 0 to 100. A VAS score of 0 indicated no pain whilst a VAS score of 100 indicated worst possible pain. Change in pain scores were calculated by subtracting week 5 values from week 13 values.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Wound Infection</measure>
    <time_frame>Weeks 5 to 13</time_frame>
    <description>Median number of wound infections per patient (as demonstrated by clinical symptoms) from beginning of treatment (week 5) and end of treatment (week 13).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Non-serious Adverse Events in Each Group</measure>
    <time_frame>Week 5 to 13</time_frame>
    <description>Adverse events (AEs) were defined as any undesirable clinical occurrence in a subject whether it is thought to be related to the investigational device or not.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wound Recurrence Rate</measure>
    <time_frame>90 days after time of healing</time_frame>
    <description>Patients whose wound has healed (defined as 100% epithelialisation with no scab present) before or at the end of treatment will be asked 90 days after date of healing if their wound has remained closed.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Varicose Ulcer</condition>
  <arm_group>
    <arm_group_label>Standard Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard treatment for VLUs is administered once a week, i.e. compression bandaging and non-adherent dressing, with debridement if required.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MIST and Standard Care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MIST ultrasound therapy is applied for between 3 and 12 minutes (depending on wound size) 3 times a week in combination with standard treatment for VLUs of compression bandaging and non-adherent dressing change 3 times a week, with debridement as required.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MIST ultrasound therapy</intervention_name>
    <description>Low frequency, non-contact ultrasound system delivering therapeutic ultrasound via a fine saline mist to the wound bed.</description>
    <arm_group_label>MIST and Standard Care</arm_group_label>
    <other_name>MIST non-contact low-frequecy ultrasound device</other_name>
    <other_name>MIST</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard Care</intervention_name>
    <description>Compression bandaging, non-adherent dressing, and debridement if required.</description>
    <arm_group_label>MIST and Standard Care</arm_group_label>
    <arm_group_label>Standard Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Venous leg ulcers (as diagnosed by the clinician)&#xD;
&#xD;
          -  Ankle Brachial Pressure Index (ABPI) &gt;0.8&#xD;
&#xD;
          -  If multiple ulcers are present treat largest ulcer only (index ulcer) with minimum&#xD;
             distance of 1 cm between index ulcer and any other ulcer&#xD;
&#xD;
          -  18 years or older&#xD;
&#xD;
          -  Ulcer size of 5 cm^2 - 100 cm^2 (with no longest length being greater than 10 cm) at&#xD;
             randomisation point (week 5)&#xD;
&#xD;
          -  Mobile enough to attend clinic&#xD;
&#xD;
          -  Index ulcer between 6 weeks and 5 years duration prior to screening date&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled diabetes (Hba1c ≥12%) as tested within the past 3 months&#xD;
&#xD;
          -  Index ulcer has active infection on day of inclusion requiring use or oral or IV&#xD;
             antibiotics&#xD;
&#xD;
          -  Renal failure&#xD;
&#xD;
          -  Index ulcer has exposed tendons, ligaments, muscle, or bone&#xD;
&#xD;
          -  Osteomyelitis or cellulitis or gangrene in study limb&#xD;
&#xD;
          -  Subjects with amputation above a trans metatarsal amputation (TMA) in the study limb&#xD;
&#xD;
          -  Subjects with active malignancy on the study limb&#xD;
&#xD;
          -  Index ulcer that is of arterial disease aetiology&#xD;
&#xD;
          -  Females of child bearing potential who are not willing to use a method of highly&#xD;
             effective contraception during the entire study&#xD;
&#xD;
          -  Planned vascular surgery, angioplasty, or thrombolysis procedures within the study&#xD;
             period, or 6 weeks post-operatively&#xD;
&#xD;
          -  Planned surgical procedure during the study period for the index wound&#xD;
&#xD;
          -  Prior skin replacement, negative pressure therapy, ultrasound therapy applied to the&#xD;
             index wound 2 weeks before screening&#xD;
&#xD;
          -  Oral or IV antibiotics within 48 hours of baseline measurements&#xD;
&#xD;
          -  Growth factor therapy within previous 14 days of screening date&#xD;
&#xD;
          -  Currently receiving or has received radiation or chemotherapy within 3 months of&#xD;
             randomisation&#xD;
&#xD;
          -  Pregnant or breast feeding women&#xD;
&#xD;
          -  Subject is currently enrolled or has been enrolled in the last 30 days in another&#xD;
             investigational device or drug trial&#xD;
&#xD;
          -  Subject's wound would require ultrasound near an electronic implant or prosthesis&#xD;
&#xD;
          -  Subjects lacking capacity to provide informed consent.&#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>Keith G Harding, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wound Healing Research Unit, Cardiff University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Wound Healing Research Unit, Cardiff University</name>
      <address>
        <city>Cardiff</city>
        <zip>CF14 4XN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>August 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 24, 2012</study_first_posted>
  <results_first_submitted>June 4, 2015</results_first_submitted>
  <results_first_submitted_qc>July 29, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 26, 2015</results_first_posted>
  <last_update_submitted>July 29, 2015</last_update_submitted>
  <last_update_submitted_qc>July 29, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 26, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cardiff University</investigator_affiliation>
    <investigator_full_name>Professor Keith G Harding</investigator_full_name>
    <investigator_title>Director - Institute for Translation, Innovation, Methodology and Engagement (TIME)</investigator_title>
  </responsible_party>
  <keyword>Venous Leg Ulcer</keyword>
  <keyword>Varicose Ulcer</keyword>
  <keyword>Chronic ulcer</keyword>
  <keyword>Chronic wound</keyword>
  <keyword>Ultrasound therapy</keyword>
  <keyword>MIST device</keyword>
  <keyword>Wound healing</keyword>
  <keyword>Low frequency non contact ultrasound</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>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Study procedures took place in a single dedicated unit specialising in wound healing research, between August 2012 and November 2013.</recruitment_details>
      <pre_assignment_details>All enrolled patients received 4 weeks of SOC prior to random allocation (run-in phase). Patients whose wounds reduced by &gt;40% in the first 4 weeks were withdrawn and did not progress to random allocation.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Standard of Care</title>
          <description>Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.</description>
        </group>
        <group group_id="P2">
          <title>NLFU and Standard of Care</title>
          <description>Non-contact low frequency ultrasound (NLFU) using MIST ultrasound therapy is applied for between 3 and 12 minutes (depending on wound size) 3 times a week in combination with standard treatment for VLUs of compression bandaging and non-adherent dressing change 3 times a week, with debridement as required.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>4 Week run-in Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Not eligible</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>12 Week Treatment Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Standard of Care</title>
          <description>Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.</description>
        </group>
        <group group_id="B2">
          <title>NLFU and Standard of Care</title>
          <description>Non-contact low frequency ultrasound (NLFU) using MIST ultrasound therapy is applied for between 3 and 12 minutes (depending on wound size) 3 times a week in combination with standard treatment for VLUs of compression bandaging and non-adherent dressing change 3 times a week, with debridement as required.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="19"/>
            <count group_id="B2" value="17"/>
            <count group_id="B3" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68.2" spread="12.2"/>
                    <measurement group_id="B2" value="70.5" spread="12.7"/>
                    <measurement group_id="B3" value="69" spread="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>History of leg ulceration (months)</title>
          <units>months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="94.7" spread="83.2"/>
                    <measurement group_id="B2" value="109.7" spread="112.2"/>
                    <measurement group_id="B3" value="101.8" spread="96.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Index ulcer duration (months)</title>
          <units>months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.3" spread="18.5"/>
                    <measurement group_id="B2" value="15.7" spread="12.0"/>
                    <measurement group_id="B3" value="19" spread="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Wound size at enrolment (cm^2)</title>
          <units>cm^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19.4" spread="14.9"/>
                    <measurement group_id="B2" value="15.9" spread="9.9"/>
                    <measurement group_id="B3" value="17.8" spread="12.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Change in wound size during run-in phase (%)</title>
          <units>percentage change in wound area</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-13.0" spread="25.2"/>
                    <measurement group_id="B2" value="-10.9" spread="23.9"/>
                    <measurement group_id="B3" value="-12.0" spread="24.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage Change in Wound Area</title>
        <description>Wound area is measured weekly using a digital wound imaging device. The wound boundary is digitally traced by a blinded assessor. Percentage and actual change in wound area between start of treatment (week 5) and end of treatment (week 13) is evaluated.</description>
        <time_frame>Week 5 to 13</time_frame>
        <population>All patients included in the analysis; Intention to treat (ITT); Values have been adjusted for the influence of the covariate (wound area at the start of treatment)</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care</title>
            <description>Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.</description>
          </group>
          <group group_id="O2">
            <title>NLFU and Standard of Care</title>
            <description>Non-contact low frequency ultrasound (NLFU) using MIST ultrasound therapy is applied for between 3 and 12 minutes (depending on wound size) 3 times a week in combination with standard treatment for VLUs of compression bandaging and non-adherent dressing change 3 times a week, with debridement as required.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change in Wound Area</title>
          <description>Wound area is measured weekly using a digital wound imaging device. The wound boundary is digitally traced by a blinded assessor. Percentage and actual change in wound area between start of treatment (week 5) and end of treatment (week 13) is evaluated.</description>
          <population>All patients included in the analysis; Intention to treat (ITT); Values have been adjusted for the influence of the covariate (wound area at the start of treatment)</population>
          <units>percentage change in wound area</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-39.2" spread="38.0"/>
                    <measurement group_id="O2" value="-46.6" spread="38.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The study was powered to detect a difference in the change in wound area of 20% between the two arms with a two sided significance level and power of 90%. A standard deviation of 17.5% came from published literature. A minimum of 17 patients in each arm was required.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.565</p_value>
            <p_value_desc>ANCOVA was used to analyse differences between the NLFU+SOC and SOC arms of the primary endpoint, percentage change in wound area from baseline (week 5) to final visit (week 13). Patients' baseline (week 5) wound area was used as the covariate.</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-7.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-33.4</ci_lower_limit>
            <ci_upper_limit>18.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Overall Health Related Quality of Life (HRQoL) From Week 1 (Start) and Week 13 (Exit)</title>
        <description>On the first and final visit participants were invited to complete a Cardiff Wound Impact Schedule (CWIS) a validated questionnaire designed to measure the impact of chronic wounds on patient health-related quality of life (HRQoL). The overall HRQoL question asks patients to rate their overall quality of life over the past week by circling a number between 0 and 10. Low scores indicate poor quality of life, and high score indicate good quality of life. Change in HRQoL was calculated by subtracting week 1 values from week 13 values.&#xD;
CWIS has been validated in the following paper: Price and Harding (2004) The Cardiff Wound Impact Schedule: the development of a condition specific questionnaire to assess health-related quality of life in patients with chronic wounds. International Wound Journal 1(1):10-17</description>
        <time_frame>Week 1 (start) and week 13 (exit)</time_frame>
        <population>All patients were analysed by ITT</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care</title>
            <description>Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.</description>
          </group>
          <group group_id="O2">
            <title>NLFU and Standard of Care</title>
            <description>Non-contact low frequency ultrasound (NLFU) using MIST ultrasound therapy is applied for between 3 and 12 minutes (depending on wound size) 3 times a week in combination with standard treatment for VLUs of compression bandaging and non-adherent dressing change 3 times a week, with debridement as required.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Overall Health Related Quality of Life (HRQoL) From Week 1 (Start) and Week 13 (Exit)</title>
          <description>On the first and final visit participants were invited to complete a Cardiff Wound Impact Schedule (CWIS) a validated questionnaire designed to measure the impact of chronic wounds on patient health-related quality of life (HRQoL). The overall HRQoL question asks patients to rate their overall quality of life over the past week by circling a number between 0 and 10. Low scores indicate poor quality of life, and high score indicate good quality of life. Change in HRQoL was calculated by subtracting week 1 values from week 13 values.&#xD;
CWIS has been validated in the following paper: Price and Harding (2004) The Cardiff Wound Impact Schedule: the development of a condition specific questionnaire to assess health-related quality of life in patients with chronic wounds. International Wound Journal 1(1):10-17</description>
          <population>All patients were analysed by ITT</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="-1" upper_limit="1"/>
                    <measurement group_id="O2" value="-1" lower_limit="-2" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>ANCOVA was used for change in HRQoL from week 1 to week 13 (with week 1 HRQoL score as the covariate).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.490</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Ulcer Pain Between Week 5 (Randomisation) and Week 13 (Exit)</title>
        <description>Pain was scored by each patient on a visual analogue score (VAS) from 0 to 100. A VAS score of 0 indicated no pain whilst a VAS score of 100 indicated worst possible pain. Change in pain scores were calculated by subtracting week 5 values from week 13 values.</description>
        <time_frame>Weeks 5 to 13</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care</title>
            <description>Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.</description>
          </group>
          <group group_id="O2">
            <title>NLFU and Standard of Care</title>
            <description>Non-contact low frequency ultrasound (NLFU) using MIST ultrasound therapy is applied for between 3 and 12 minutes (depending on wound size) 3 times a week in combination with standard treatment for VLUs of compression bandaging and non-adherent dressing change 3 times a week, with debridement as required.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Ulcer Pain Between Week 5 (Randomisation) and Week 13 (Exit)</title>
          <description>Pain was scored by each patient on a visual analogue score (VAS) from 0 to 100. A VAS score of 0 indicated no pain whilst a VAS score of 100 indicated worst possible pain. Change in pain scores were calculated by subtracting week 5 values from week 13 values.</description>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.27" spread="14.84"/>
                    <measurement group_id="O2" value="-14.35" spread="14.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>ANCOVA was used for change in pain score (VAS) from week 5 to week 13 (covariate was baseline pain score).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.078</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-9.08</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-19.23</ci_lower_limit>
            <ci_upper_limit>1.06</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Wound Infection</title>
        <description>Median number of wound infections per patient (as demonstrated by clinical symptoms) from beginning of treatment (week 5) and end of treatment (week 13).</description>
        <time_frame>Weeks 5 to 13</time_frame>
        <population>All patients included; ITT.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care</title>
            <description>Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.</description>
          </group>
          <group group_id="O2">
            <title>NLFU and Standard of Care</title>
            <description>Non-contact low frequency ultrasound (NLFU) using MIST ultrasound therapy is applied for between 3 and 12 minutes (depending on wound size) 3 times a week in combination with standard treatment for VLUs of compression bandaging and non-adherent dressing change 3 times a week, with debridement as required.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Wound Infection</title>
          <description>Median number of wound infections per patient (as demonstrated by clinical symptoms) from beginning of treatment (week 5) and end of treatment (week 13).</description>
          <population>All patients included; ITT.</population>
          <units>Number of infections per patient</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="1" upper_limit="3"/>
                    <measurement group_id="O2" value="2" lower_limit="0" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change in number of infections were not normally distributed and differences between the arms were tested using the non-parametric Mann-Whitney U test.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.346</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Non-serious Adverse Events in Each Group</title>
        <description>Adverse events (AEs) were defined as any undesirable clinical occurrence in a subject whether it is thought to be related to the investigational device or not.</description>
        <time_frame>Week 5 to 13</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care</title>
            <description>Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.</description>
          </group>
          <group group_id="O2">
            <title>NLFU and Standard of Care</title>
            <description>Non-contact low frequency ultrasound (NLFU) using MIST ultrasound therapy is applied for between 3 and 12 minutes (depending on wound size) 3 times a week in combination with standard treatment for VLUs of compression bandaging and non-adherent dressing change 3 times a week, with debridement as required.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Non-serious Adverse Events in Each Group</title>
          <description>Adverse events (AEs) were defined as any undesirable clinical occurrence in a subject whether it is thought to be related to the investigational device or not.</description>
          <units>Number of non-serious AEs</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70"/>
                    <measurement group_id="O2" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Actual Change in Wound Area</title>
        <description>Wound area is measured weekly using a digital wound imaging device. The wound boundary is digitally traced by a blinded assessor. Percentage and actual change in wound area between start of treatment (week 5) and end of treatment (week 13) is evaluated.</description>
        <time_frame>Week 5 to 13</time_frame>
        <population>As previous</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care</title>
            <description>Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.</description>
          </group>
          <group group_id="O2">
            <title>NLFU and Standard of Care</title>
            <description>Non-contact low frequency ultrasound (NLFU) using MIST ultrasound therapy is applied for between 3 and 12 minutes (depending on wound size) 3 times a week in combination with standard treatment for VLUs of compression bandaging and non-adherent dressing change 3 times a week, with debridement as required.</description>
          </group>
        </group_list>
        <measure>
          <title>Actual Change in Wound Area</title>
          <description>Wound area is measured weekly using a digital wound imaging device. The wound boundary is digitally traced by a blinded assessor. Percentage and actual change in wound area between start of treatment (week 5) and end of treatment (week 13) is evaluated.</description>
          <population>As previous</population>
          <units>cm2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.3" spread="5.5"/>
                    <measurement group_id="O2" value="-6.2" spread="5.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.618</p_value>
            <method>ANCOVA</method>
            <method_desc>Patients' baseline (week 5) wound area was used as the covariate.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.7</ci_lower_limit>
            <ci_upper_limit>2.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Wound Recurrence Rate</title>
        <description>Patients whose wound has healed (defined as 100% epithelialisation with no scab present) before or at the end of treatment will be asked 90 days after date of healing if their wound has remained closed.</description>
        <time_frame>90 days after time of healing</time_frame>
        <population>Three patients healed during the study period (one NLFU+SOC patient healed after 7 weeks and one after 8 weeks of NLFU+SOC treatment, and one patient who received standard care alone healed after 4 weeks). All three of these patients remained healed 90 days after the end of their study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care</title>
            <description>Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.</description>
          </group>
          <group group_id="O2">
            <title>NLFU and Standard of Care</title>
            <description>Non-contact low frequency ultrasound (NLFU) using MIST ultrasound therapy is applied for between 3 and 12 minutes (depending on wound size) 3 times a week in combination with standard treatment for VLUs of compression bandaging and non-adherent dressing change 3 times a week, with debridement as required.</description>
          </group>
        </group_list>
        <measure>
          <title>Wound Recurrence Rate</title>
          <description>Patients whose wound has healed (defined as 100% epithelialisation with no scab present) before or at the end of treatment will be asked 90 days after date of healing if their wound has remained closed.</description>
          <population>Three patients healed during the study period (one NLFU+SOC patient healed after 7 weeks and one after 8 weeks of NLFU+SOC treatment, and one patient who received standard care alone healed after 4 weeks). All three of these patients remained healed 90 days after the end of their study treatment.</population>
          <units>Number of wounds remained healed</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Study period of 13 weeks</time_frame>
      <desc>Any undesirable clinical occurrence in a subject whether it is thought to be related to the NLFU or not. All subjects experiencing AEs were monitored until symptoms subside or until there is a satisfactory explanation for the changes observed. The nature of venous leg ulcers meant that AEs were common in both the SOC and NLFU groups</desc>
      <group_list>
        <group group_id="E1">
          <title>Standard of Care</title>
          <description>Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.</description>
        </group>
        <group group_id="E2">
          <title>NLFU and Standard of Care</title>
          <description>Non-contact low frequency ultrasound (NLFU) using MIST ultrasound therapy is applied for between 3 and 12 minutes (depending on wound size) 3 times a week in combination with standard treatment for VLUs of compression bandaging and non-adherent dressing change 3 times a week, with debridement as required.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>All adverse events</sub_title>
                <description>Any undesirable clinical occurrence in a subject whether it is thought to be related to device or not. The recording of adverse events means that specific AE terms cannot be included. See outcome relating to infection.</description>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Difference in treatment frequency between the groups which could potentially bias results.&#xD;
Standard deviation proved to be larger than estimated from the available literature which resulted in the study having reduced statistical power.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr Judith White</name_or_title>
      <organization>Cardiff and Vale University Health Board</organization>
      <phone>02920744771</phone>
      <email>judith.white3@wales.nhs.uk</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01671748
org study id: 12-SUR-5323
nct id: NCT01671748
lead sponsor: 
collaborator: 
has dmc: No
Chronic venous leg ulcers (VLUs) impact negatively on patients' quality of life. Standard
      treatment in the UK for patients with VLUs is compression bandaging or stockings. The MIST
      ultrasound system is a noncontact device which delivers low frequency ultrasound through a
      gentle saline mist directed at a patient's wound. This study aims to determine whether the
      use of the MIST device used in combination with standard treatments can improve healing of
      VLUs compared to UK standard practice. This will be assessed by measuring any reduction in
      wound size in the two groups after receiving 8 weeks of either Standard Care once a week or
      MIST combined with Standard Care three times a week.
Venous leg ulcers (VLUs) are wounds which are often chronic and difficult to heal. VLUs
      affect between 1 and 3.2 people per 1000; they cause pain, reduced mobility and impact
      negatively on patients' quality of life (QoL). Standard treatment for patients with VLUs is
      the application of strong, sustained compression with bandages or stockings. This
      pragmatically-designed study aims to determine whether the use of a device called MIST used
      in combination with standard treatments can improve healing of VLUs compared to UK standard
      practice. It will also show whether the MIST regimen improves participants' QoL and reduces
      the incidence of infection.

      The MIST ultrasound system is a non-contact device which delivers low-frequency ultrasound
      through a gentle saline mist directed at a patient's wound. Patients (over 18 years old) will
      be invited to take part in this study if they have had a VLU for 6 weeks or more, which
      measures between 5 and 100 cm^2, and is not infected. Participants with diabetes must show
      good blood glucose control, and those with underlying chronic disorders which may affect
      wound healing will be excluded.

      All study participants will receive four weeks of standard treatment once a week at a single
      clinic at the Wound Healing Research Unit (WHRU), University Hospital of Wales. Patients
      whose wounds reduce by more than 40% during this time will be withdrawn from the study.
      Remaining patients will be randomly allocated to either the active group or the control group
      to receive a further eight weeks of treatment. Participants in the active group will receive
      treatment with the MIST device three times a week, as well as standard care (change of
      compression bandage and dressings) three times a week. The control group will receive UK
      standard care (which is dressing and compression bandage change at least once a week). The
      participants' ulcers will be measured and photographed once a week, and the wound
      characteristics will be assessed. Changes in participants' health related QoL will be
      assessed using a questionnaire at the beginning and end of the trial. Wound recurrence rates
      90 days after the end of the treatment will be assessed by telephoning patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Percentage Change in Wound Area
time frame: Week 5 to 13
description: Wound area is measured weekly using a digital wound imaging device. The wound boundary is digitally traced by a blinded assessor. Percentage and actual change in wound area between start of treatment (week 5) and end of treatment (week 13) is evaluated.
measure: Actual Change in Wound Area
time frame: Week 5 to 13
description: Wound area is measured weekly using a digital wound imaging device. The wound boundary is digitally traced by a blinded assessor. Percentage and actual change in wound area between start of treatment (week 5) and end of treatment (week 13) is evaluated.
measure: Change in Overall Health Related Quality of Life (HRQoL) From Week 1 (Start) and Week 13 (Exit)
time frame: Week 1 (start) and week 13 (exit)
description: On the first and final visit participants were invited to complete a Cardiff Wound Impact Schedule (CWIS) a validated questionnaire designed to measure the impact of chronic wounds on patient health-related quality of life (HRQoL). The overall HRQoL question asks patients to rate their overall quality of life over the past week by circling a number between 0 and 10. Low scores indicate poor quality of life, and high score indicate good quality of life. Change in HRQoL was calculated by subtracting week 1 values from week 13 values.
CWIS has been validated in the following paper: Price and Harding (2004) The Cardiff Wound Impact Schedule: the development of a condition specific questionnaire to assess health-related quality of life in patients with chronic wounds. International Wound Journal 1(1):10-17
measure: Change in Ulcer Pain Between Week 5 (Randomisation) and Week 13 (Exit)
time frame: Weeks 5 to 13
description: Pain was scored by each patient on a visual analogue score (VAS) from 0 to 100. A VAS score of 0 indicated no pain whilst a VAS score of 100 indicated worst possible pain. Change in pain scores were calculated by subtracting week 5 values from week 13 values.
measure: Incidence of Wound Infection
time frame: Weeks 5 to 13
description: Median number of wound infections per patient (as demonstrated by clinical symptoms) from beginning of treatment (week 5) and end of treatment (week 13).
measure: Number of Non-serious Adverse Events in Each Group
time frame: Week 5 to 13
description: Adverse events (AEs) were defined as any undesirable clinical occurrence in a subject whether it is thought to be related to the investigational device or not.
measure: Wound Recurrence Rate
time frame: 90 days after time of healing
description: Patients whose wound has healed (defined as 100% epithelialisation with no scab present) before or at the end of treatment will be asked 90 days after date of healing if their wound has remained closed.
arm group label: Standard Care
arm group type: Active Comparator
description: Standard treatment for VLUs is administered once a week, i.e. compression bandaging and non-adherent dressing, with debridement if required.
arm group label: MIST and Standard Care
arm group type: Experimental
description: MIST ultrasound therapy is applied for between 3 and 12 minutes (depending on wound size) 3 times a week in combination with standard treatment for VLUs of compression bandaging and non-adherent dressing change 3 times a week, with debridement as required.
intervention type: Device
intervention name: MIST ultrasound therapy
description: Low frequency, non-contact ultrasound system delivering therapeutic ultrasound via a fine saline mist to the wound bed.
arm group label: MIST and Standard Care
other name: MIST non-contact low-frequecy ultrasound device
other name: MIST
intervention type: Other
intervention name: Standard Care
description: Compression bandaging, non-adherent dressing, and debridement if required.
arm group label: MIST and Standard Care
arm group label: Standard Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Keith G Harding, Professor
role: Principal Investigator
affiliation: Wound Healing Research Unit, Cardiff University
facility: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: Cardiff University
investigator full name: Professor Keith G Harding
investigator title: Director - Institute for Translation, Innovation, Methodology and Engagement (TIME)
mesh term: Varicose Ulcer
mesh term: Leg Ulcer
mesh term: Ulcer
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Difference in treatment frequency between the groups which could potentially bias results.
Standard deviation proved to be larger than estimated from the available literature which resulted in the study having reduced statistical power.
point of contact: 