<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/NCT03006185</url>
  </required_header>
  <id_info>
    <org_study_id>H-16023991</org_study_id>
    <secondary_id>2015-002331-18</secondary_id>
    <nct_id>NCT03006185</nct_id>
  </id_info>
  <brief_title>Laser and Microdermabrasion Before Photodynamic Therapy for Actinic Keratoses in Field-cancerized Skin</brief_title>
  <official_title>Pretreatment With Ablative Fractional Laser and Microdermabrasion Before Photodynamic Therapy for Actinic Keratoses in Field-cancerized Skin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bispebjerg Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Galderma R&amp;D</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Bispebjerg Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Comparison of treatment efficacy and safety of pretreatment with ablative fractional laser&#xD;
      versus microdermabrasion combined with large-area photodynamic therapy with methyl&#xD;
      aminolevulinate for actinic keratoses&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For each study participant, two test areas (A and B) are demarcated in the same anatomical&#xD;
      region, with each area containing no less than 5 actinic keratoses (AKs). Test areas are&#xD;
      randomized to receive skin pretreatment of EITHER ablative fractional laser OR&#xD;
      microdermabrasion prior to photodynamic therapy using methyl aminolevulinate.&#xD;
&#xD;
      Efficacy, local skin reactions and safety of both test areas are evaluated over a 12-15 week&#xD;
      follow up period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2016</start_date>
  <completion_date type="Actual">March 1, 2017</completion_date>
  <primary_completion_date type="Actual">November 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Complete Clearance (%) of Actinic Keratoses (AKs)</measure>
    <time_frame>12-15 weeks post-treatment</time_frame>
    <description>Percentage clearance of baseline actinic keratoses (AKs), determined by the ratio of AK lesions that are clinically resolved 12-15 weeks after treatment compared to the AK number at baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>New Actinic Keratoses (AKs)</measure>
    <time_frame>12-15 weeks post-treatment</time_frame>
    <description>Number of new actinic keratoses (AKs) identified clinically 12-15 weeks after treatment and that were not present at the baseline evaluation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of Local Skin Reactions (LSRs)</measure>
    <time_frame>Day 3-6 post treatment</time_frame>
    <description>Local skin reactions scale (min:0; better and max: 3; worse) used to grade each of the following parameters: erythema, edema, crusting, pustules, ulceration and scabbing, scaling.&#xD;
The severity of each evaluated clinically on a 4-point scale where 0 = none, 1= mild, 2= moderate and 3= severe.&#xD;
With 7 parameters the sum of all scores will produce a maximum composite score of 21.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of Sun Damage</measure>
    <time_frame>12-15 weeks post-treatment</time_frame>
    <description>Sun damage is evaluated clinically on a 4 point scale where 0 = none, 1= mild, 2= moderate and 3= severe sun damage.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-related Pain</measure>
    <time_frame>during treatment (day 0)</time_frame>
    <description>Patient-reported pain during treatments is evaluated using the visual analog scale (VAS) where 0= no pain and 10= worst imaginable pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-related Side Effects</measure>
    <time_frame>up to 12-15 weeks post-treatment</time_frame>
    <description>Side effects are evaluated over the course 12-15 weeks following treatment. In addition to unforeseen adverse events, specific side effects including the clinical presence of infection, scarring, hypopigmentation and hyperpigmentation are recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigator-reported Cosmesis (Clinical Evaluation)</measure>
    <time_frame>12-15 weeks post-treatment</time_frame>
    <description>Cosmetic appearance of treated areas is evaluated by investigators clinically (scores on a scale) using a 4-point scale where 0 = none, 1= acceptable, 2= good and 3= excellent outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient-reported Cosmesis</measure>
    <time_frame>12-15 weeks post-treatment</time_frame>
    <description>Cosmetic appearance is evaluated by patients at the end of the study (scores on a scale) using a 4 point scale where 0 = none, 1= acceptable, 2= good and 3= excellent</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Pretreatment Preference</measure>
    <time_frame>12-15 weeks post-treatment</time_frame>
    <description>Patients were asked to report which pretreatment they preferred: Laser, microdermabrasion, or no preference</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Actinic Keratosis</condition>
  <condition>Sun Damaged Skin</condition>
  <condition>Solar Keratosis</condition>
  <condition>Solar Skin Damage</condition>
  <arm_group>
    <arm_group_label>Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>WIthin each participant, two 50 cm2 adjacent test areas were randomized to laser or microdermabrasion pretreatment prior to daylight photodynamic therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Ablative Fractional Carbon Dioxide (CO2) Laser</intervention_name>
    <description>One 50 cm2 test area was randomized to pretreatment using a fractional 2940 nm Er:YAG laser (Joule®; Sciton Inc., Palo Alto, CA, USA). To remove hyperkeratosis, a fully-ablative 4 mm handpiece was optionally applied, followed by a single pass of a fractional Profrax 430 handpiece for all AKs. Subsequent field treatment consisted of a single pass of the Profrax 430 handpiece over the entire test area. Immediately after pretreatment, a 0.5 mm layer of methyl aminolevulinate (Metvix ® cream 16%; Galderma, Paris, France) was applied. After 30 minutes, patients were exposed to 2 hours of ambient daylight, according to approved procedure. After light exposure, cream was wiped off and test areas were covered for the remainder of the day.</description>
    <arm_group_label>Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Microdermabrasion</intervention_name>
    <description>Another adjacent 50 cm2 test area was exposed to microdermabrasion using an MD pad with 58.5 µm-diameter particles (Ambu® Skin Prep Pads 2121M; Ambu A/S, Ballerup, Denmark). Lesion-directed treatment consisted of an increasing number of swipes concentrated to AK lesions. During field treatment, multiple swipes were applied in perpendicular directions over the entire test area. Immediately after pretreatment, a 0.5 mm layer of methyl aminolevulinate (Metvix ® cream 16%; Galderma, Paris, France) was applied. After 30 minutes, patients were exposed to 2 hours of ambient daylight, according to approved procedure. After light exposure, cream was wiped off and test areas were covered for the remainder of the day.</description>
    <arm_group_label>Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with two skin areas of at least 50 cm2 with a minimum of 5 actinic keratoses&#xD;
             (AKs) grade I-III, chronically sun damaged &quot;field&quot; changes in one of the following&#xD;
             anatomical regions: face, scalp, upper chest.&#xD;
&#xD;
          -  Patients who have given written informed consent and are believed to be capable of&#xD;
             following the study protocol.&#xD;
&#xD;
          -  Fertile women must have a negative pregnancy test (urine-hCG) at the time of inclusion&#xD;
             and use anti-contraception (oral contraceptives, intrauterine device, gestagen depot&#xD;
             injection, subdermal implantation, vaginal ring, transdermal depot bandage or&#xD;
             sterilisation) during the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients that have within the last month received local treatment in the test areas.&#xD;
&#xD;
          -  Pregnant or nursing patients.&#xD;
&#xD;
          -  Patients with porphyria&#xD;
&#xD;
          -  Patients with skin cancer, keratoacanthoma, or other infiltrating tumors within the&#xD;
             test areas.&#xD;
&#xD;
          -  Patients with a tendency to develop hypertrophic scars or keloids.&#xD;
&#xD;
          -  Patients with a known allergy to Metvix cream&#xD;
&#xD;
          -  Patients that are believe unlikely to follow the study protocol.&#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>Merete Haedersdal, MD, Dr. Med</last_name>
    <role>Principal Investigator</role>
    <affiliation>Bispebjerg Hospital</affiliation>
  </overall_official>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>December 9, 2016</study_first_submitted>
  <study_first_submitted_qc>December 26, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 30, 2016</study_first_posted>
  <results_first_submitted>January 20, 2018</results_first_submitted>
  <results_first_submitted_qc>September 13, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 28, 2022</results_first_posted>
  <last_update_submitted>September 13, 2022</last_update_submitted>
  <last_update_submitted_qc>September 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Bispebjerg Hospital</investigator_affiliation>
    <investigator_full_name>Merete Haedersdal</investigator_full_name>
    <investigator_title>Professor and Senior Physician</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Keratosis, Actinic</mesh_term>
    <mesh_term>Keratosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion</title>
          <description>Intra-individual design. &quot;All study participants&quot; are grouped into a single arm. Two adjacent skin areas (test areas) on each participant was allocated through randomization to two different interventions: 1) Pretreatment with Ablative Fractional (AFL) CO2 laser OR 2) Microdermabrasion (MD) prior to standard daylight photodynamic therapy.&#xD;
Description of intervention: Ablative Fractional CO2 laser: CO2 laser treatment is randomly allocated to one of two tests areas within each study participant. Laser treatment consists of targeted ablation of actinic keratoses and field laser treatment of the entire test area. After laser treatment, application of methyl aminolevulinate (MAL), a topical photosensitizing agent, is performed. The test area thereafter undergoes 2 hours of daylight photodynamic therapy.&#xD;
Microdermabrasion: Microdermabrasion (processing of the skin with a sandpaper-like material) is randomly allocated to one of two tests areas in each study participant. Microdermabrasion treatment consists of targeted treatment of actinic keratoses and field treatment of the entire test area. Afterwards, application of methyl aminolevulinate (MAL), a topical photosensitizing agent, is performed. The test area then undergoes 2 hours of daylight photodynamic therapy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18">Since all participants had two test areas each, all participants received both interventions (18 test areas received CO2 and 18 test areas received microdermabrasion)</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Number of Test Areas Recieving AFL</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Number of Test Areas Receiving MD</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Each participant had two skin areas that individually were randomized to receive either microdermabrasion or ablative fractional laser prior to photodynamic therapy. Thus, with 18 participants, we had 36 test areas.</population>
      <group_list>
        <group group_id="B1">
          <title>Split Person Design: Pretreatment With Ablative Fractional Carbon Dioxide Laser or Microdermabrasion</title>
          <description>Two 50 cm2 test areas (Test Area A and B) are demarcated on the skin of each study participant. One test area is randomized to receive the intervention: Ablative Fractional Carbon Dioxide (CO2) Laser prior to standard daylight photodynamic therapy. The other test area is randomized to receive the intervention: microdermabrasion prior to standard daylight photodynamic therapy.&#xD;
Ablative Fractional Carbon Dioxide (CO2) Laser: Ablative Fractional Carbon Dioxide (CO2) Laser treatment is randomly allocated to one of two tests areas in each study participant. Laser treatment consists of targeted ablation of actinic keratoses and field laser treatment of the entire test area. After laser treatment, application of methyl aminolevulinate (MAL), a topical photosensitising agent, is performed. The test area thereafter undergoes 2 hours of daylight photodynamic therapy.&#xD;
Microdermabrasion: Microdermabrasion (processing of the skin with a sandpaper-like material) is randomly allocated to one of two tests areas in each study participant. Microdermabrasion treatment consists of targeted treatment of actinic keratoses and field treatment of the entire test area. Afterwards, application of methyl aminolevulinate (MAL), a topical photosensitising agent, is performed. The test area then undergoes 2 hours of daylight photodynamic therapy.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
          </count_list>
        </analyzed>
        <analyzed>
          <units>Skin areas</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="72.5" lower_limit="52" upper_limit="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <title>Denmark</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Complete Clearance (%) of Actinic Keratoses (AKs)</title>
        <description>Percentage clearance of baseline actinic keratoses (AKs), determined by the ratio of AK lesions that are clinically resolved 12-15 weeks after treatment compared to the AK number at baseline.</description>
        <time_frame>12-15 weeks post-treatment</time_frame>
        <population>Percentage AK clearance in test areas receiving either AFL (18) or microdermabrasion (18) assisted daylight PDT treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion</title>
            <description>Intra-individual design of 18 participants. &quot;All study participants&quot; are grouped into a single arm. Two adjacent skin areas (test areas) on each participant is allocated through randomization to two different interventions: 1) Pretreatment with Ablative Fractional (AFL) CO2 laser OR 2) Microdermabrasion (MD) prior to standard daylight photodynamic therapy. Thus, each participants received both inventions (18 test areas received AFL and 18 test areas received MD).</description>
          </group>
        </group_list>
        <measure>
          <title>Complete Clearance (%) of Actinic Keratoses (AKs)</title>
          <description>Percentage clearance of baseline actinic keratoses (AKs), determined by the ratio of AK lesions that are clinically resolved 12-15 weeks after treatment compared to the AK number at baseline.</description>
          <population>Percentage AK clearance in test areas receiving either AFL (18) or microdermabrasion (18) assisted daylight PDT treatment</population>
          <units>percentage (%) of AK clearance</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <units_analyzed>Test areas</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Test areas</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ablative Fractional Laser</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81" lower_limit="53" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Microdermabrasion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60" lower_limit="24" upper_limit="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>New Actinic Keratoses (AKs)</title>
        <description>Number of new actinic keratoses (AKs) identified clinically 12-15 weeks after treatment and that were not present at the baseline evaluation.</description>
        <time_frame>12-15 weeks post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion</title>
            <description>Intra-individual design of 18 participants. &quot;All study participants&quot; are grouped into a single arm. Two adjacent skin areas (test areas) on each participant is allocated through randomization to two different interventions: 1) Pretreatment with Ablative Fractional (AFL) CO2 laser OR 2) Microdermabrasion (MD) prior to standard daylight photodynamic therapy. Thus, each participants receives both inventions (18 test areas received AFL and 18 test areas received MD).</description>
          </group>
        </group_list>
        <measure>
          <title>New Actinic Keratoses (AKs)</title>
          <description>Number of new actinic keratoses (AKs) identified clinically 12-15 weeks after treatment and that were not present at the baseline evaluation.</description>
          <units>New AK lesions</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <units_analyzed>Test areas</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Test areas</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ablative Fractional Laser</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Microdermabrasion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="0" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Severity of Local Skin Reactions (LSRs)</title>
        <description>Local skin reactions scale (min:0; better and max: 3; worse) used to grade each of the following parameters: erythema, edema, crusting, pustules, ulceration and scabbing, scaling.&#xD;
The severity of each evaluated clinically on a 4-point scale where 0 = none, 1= mild, 2= moderate and 3= severe.&#xD;
With 7 parameters the sum of all scores will produce a maximum composite score of 21.</description>
        <time_frame>Day 3-6 post treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pretreatment</title>
            <description>Two 50 cm2 test areas (Test Area A and B) are demarcated on the skin of each study participant. One test area is randomized to receive the intervention: Ablative Fractional Carbon Dioxide (CO2) Laser prior to standard daylight photodynamic therapy. The other test area is randomized to receive the intervention: microdermabrasion prior to standard daylight photodynamic therapy.&#xD;
Ablative Fractional Carbon Dioxide (CO2) Laser: Ablative Fractional Carbon Dioxide (CO2) Laser treatment is randomly allocated to one of two tests areas in each study participant. Laser treatment consists of targeted ablation of actinic keratoses and field laser treatment of the entire test area. After laser treatment, application of methyl aminolevulinate (MAL), a topical photosensitizing agent, is performed. The test area thereafter undergoes 2 hours of daylight photodynamic therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Severity of Local Skin Reactions (LSRs)</title>
          <description>Local skin reactions scale (min:0; better and max: 3; worse) used to grade each of the following parameters: erythema, edema, crusting, pustules, ulceration and scabbing, scaling.&#xD;
The severity of each evaluated clinically on a 4-point scale where 0 = none, 1= mild, 2= moderate and 3= severe.&#xD;
With 7 parameters the sum of all scores will produce a maximum composite score of 21.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <units_analyzed>Test areas</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Test areas</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ablative Frational Laser</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="5" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Microdermabrasion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="2" upper_limit="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Degree of Sun Damage</title>
        <description>Sun damage is evaluated clinically on a 4 point scale where 0 = none, 1= mild, 2= moderate and 3= severe sun damage.</description>
        <time_frame>12-15 weeks post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion</title>
            <description>Intra-individual design of 18 participants. &quot;All study participants&quot; are grouped into a single arm. Two adjacent skin areas (test areas) on each participant is allocated through randomization to two different interventions: 1) Pretreatment with Ablative Fractional (AFL) CO2 laser OR 2) Microdermabrasion (MD) prior to standard daylight photodynamic therapy. Thus, each participants receives both inventions (18 test areas received AFL and 18 test areas received MD).</description>
          </group>
        </group_list>
        <measure>
          <title>Degree of Sun Damage</title>
          <description>Sun damage is evaluated clinically on a 4 point scale where 0 = none, 1= mild, 2= moderate and 3= severe sun damage.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <units_analyzed>Skin Areas</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Skin Areas</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ablative Fractional Laser</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="0" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Microdermabrasion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="1" upper_limit="2.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment-related Pain</title>
        <description>Patient-reported pain during treatments is evaluated using the visual analog scale (VAS) where 0= no pain and 10= worst imaginable pain.</description>
        <time_frame>during treatment (day 0)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion</title>
            <description>Intra-individual design of 18 participants. &quot;All study participants&quot; are grouped into a single arm. Two adjacent skin areas (test areas) on each participant is allocated through randomization to two different interventions: 1) Pretreatment with Ablative Fractional (AFL) CO2 laser OR 2) Microdermabrasion (MD) prior to standard daylight photodynamic therapy. Thus, each participants receives both inventions (18 test areas received AFL and 18 test areas received MD).</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment-related Pain</title>
          <description>Patient-reported pain during treatments is evaluated using the visual analog scale (VAS) where 0= no pain and 10= worst imaginable pain.</description>
          <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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ablative Fractional Laser</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="2" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Microdermabrasion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="4" upper_limit="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment-related Side Effects</title>
        <description>Side effects are evaluated over the course 12-15 weeks following treatment. In addition to unforeseen adverse events, specific side effects including the clinical presence of infection, scarring, hypopigmentation and hyperpigmentation are recorded.</description>
        <time_frame>up to 12-15 weeks post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion</title>
            <description>Intra-individual design of 18 participants. &quot;All study participants&quot; are grouped into a single arm. Two adjacent skin areas (test areas) on each participant is allocated through randomization to two different interventions: 1) Pretreatment with Ablative Fractional (AFL) CO2 laser OR 2) Microdermabrasion (MD) prior to standard daylight photodynamic therapy. Thus, each participants receives both inventions (18 test areas received AFL and 18 test areas received MD).</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment-related Side Effects</title>
          <description>Side effects are evaluated over the course 12-15 weeks following treatment. In addition to unforeseen adverse events, specific side effects including the clinical presence of infection, scarring, hypopigmentation and hyperpigmentation are recorded.</description>
          <units>Local Staf infection</units>
          <param>Number</param>
          <units_analyzed>Test areas</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Test areas</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ablative Fractional Laser</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Microdermabrasion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Investigator-reported Cosmesis (Clinical Evaluation)</title>
        <description>Cosmetic appearance of treated areas is evaluated by investigators clinically (scores on a scale) using a 4-point scale where 0 = none, 1= acceptable, 2= good and 3= excellent outcome.</description>
        <time_frame>12-15 weeks post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion</title>
            <description>Intra-individual design of 18 participants. &quot;All study participants&quot; are grouped into a single arm. Two adjacent skin areas (test areas) on each participant is allocated through randomization to two different interventions: 1) Pretreatment with Ablative Fractional (AFL) CO2 laser OR 2) Microdermabrasion (MD) prior to standard daylight photodynamic therapy. Thus, each participants receives both inventions (18 test areas received AFL and 18 test areas received MD).</description>
          </group>
        </group_list>
        <measure>
          <title>Investigator-reported Cosmesis (Clinical Evaluation)</title>
          <description>Cosmetic appearance of treated areas is evaluated by investigators clinically (scores on a scale) using a 4-point scale where 0 = none, 1= acceptable, 2= good and 3= excellent outcome.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <units_analyzed>Test areas</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Test areas</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ablative Fractional Laser</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="2" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Microdermabrasion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="1.5" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient-reported Cosmesis</title>
        <description>Cosmetic appearance is evaluated by patients at the end of the study (scores on a scale) using a 4 point scale where 0 = none, 1= acceptable, 2= good and 3= excellent</description>
        <time_frame>12-15 weeks post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion</title>
            <description>Intra-individual design of 18 participants. &quot;All study participants&quot; are grouped into a single arm. Two adjacent skin areas (test areas) on each participant is allocated through randomization to two different interventions: 1) Pretreatment with Ablative Fractional (AFL) CO2 laser OR 2) Microdermabrasion (MD) prior to standard daylight photodynamic therapy. Thus, each participants receives both inventions (18 test areas received AFL and 18 test areas received MD).</description>
          </group>
        </group_list>
        <measure>
          <title>Patient-reported Cosmesis</title>
          <description>Cosmetic appearance is evaluated by patients at the end of the study (scores on a scale) using a 4 point scale where 0 = none, 1= acceptable, 2= good and 3= excellent</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <units_analyzed>Test areas</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Test areas</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ablative Fractional Laser</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="2" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Microdermabrasion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="1" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Pretreatment Preference</title>
        <description>Patients were asked to report which pretreatment they preferred: Laser, microdermabrasion, or no preference</description>
        <time_frame>12-15 weeks post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion</title>
            <description>Intra-individual design of 18 participants. &quot;All study participants&quot; are grouped into a single arm. Two adjacent skin areas (test areas) on each participant is allocated through randomization to two different interventions: 1) Pretreatment with Ablative Fractional (AFL) CO2 laser OR 2) Microdermabrasion (MD) prior to standard daylight photodynamic therapy. Thus, each participants receives both inventions (18 test areas received AFL and 18 test areas received MD).</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Pretreatment Preference</title>
          <description>Patients were asked to report which pretreatment they preferred: Laser, microdermabrasion, or no preference</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ablative Fractional Laser</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Microdermabrasion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No Preference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Split-Person: Ablative Fractional Carbon Dioxide Laser or Microdermabrasion</title>
          <description>Intra-individual design of 18 participants. &quot;All study participants&quot; are grouped into a single arm. Two adjacent skin areas (test areas) on each participant is allocated through randomization to two different interventions: 1) Pretreatment with Ablative Fractional (AFL) CO2 laser OR 2) Microdermabrasion (MD) prior to standard daylight photodynamic therapy. Thus, each participants receives both inventions (18 test areas received AFL and 18 test areas received MD).</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
              </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="3" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection in test areas treated with AFL</sub_title>
                <description>Staph aureus infection was noted in 3/18 test areas pretreated with ablative fractional laser</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Infection in test areas treated with MD</sub_title>
                <description>Staph aureus infection was noted in 1/18 test areas pretreated with microdermabrasion</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </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>
    <point_of_contact>
      <name_or_title>Emily Wenande</name_or_title>
      <organization>Bispebjerg Hospital</organization>
      <phone>+4540505590</phone>
      <email>emilycathrinew@hotmail.com</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/NCT03006185
org study id: H-16023991
secondary id: 2015-002331-18
nct id: NCT03006185
lead sponsor: 
collaborator: 
has dmc: Yes
Comparison of treatment efficacy and safety of pretreatment with ablative fractional laser
      versus microdermabrasion combined with large-area photodynamic therapy with methyl
      aminolevulinate for actinic keratoses
For each study participant, two test areas (A and B) are demarcated in the same anatomical
      region, with each area containing no less than 5 actinic keratoses (AKs). Test areas are
      randomized to receive skin pretreatment of EITHER ablative fractional laser OR
      microdermabrasion prior to photodynamic therapy using methyl aminolevulinate.

      Efficacy, local skin reactions and safety of both test areas are evaluated over a 12-15 week
      follow up period.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: Complete Clearance (%) of Actinic Keratoses (AKs)
time frame: 12-15 weeks post-treatment
description: Percentage clearance of baseline actinic keratoses (AKs), determined by the ratio of AK lesions that are clinically resolved 12-15 weeks after treatment compared to the AK number at baseline.
measure: New Actinic Keratoses (AKs)
time frame: 12-15 weeks post-treatment
description: Number of new actinic keratoses (AKs) identified clinically 12-15 weeks after treatment and that were not present at the baseline evaluation.
measure: Severity of Local Skin Reactions (LSRs)
time frame: Day 3-6 post treatment
description: Local skin reactions scale (min:0; better and max: 3; worse) used to grade each of the following parameters: erythema, edema, crusting, pustules, ulceration and scabbing, scaling.
The severity of each evaluated clinically on a 4-point scale where 0 = none, 1= mild, 2= moderate and 3= severe.
With 7 parameters the sum of all scores will produce a maximum composite score of 21.
measure: Degree of Sun Damage
time frame: 12-15 weeks post-treatment
description: Sun damage is evaluated clinically on a 4 point scale where 0 = none, 1= mild, 2= moderate and 3= severe sun damage.
measure: Treatment-related Pain
time frame: during treatment (day 0)
description: Patient-reported pain during treatments is evaluated using the visual analog scale (VAS) where 0= no pain and 10= worst imaginable pain.
measure: Treatment-related Side Effects
time frame: up to 12-15 weeks post-treatment
description: Side effects are evaluated over the course 12-15 weeks following treatment. In addition to unforeseen adverse events, specific side effects including the clinical presence of infection, scarring, hypopigmentation and hyperpigmentation are recorded.
measure: Investigator-reported Cosmesis (Clinical Evaluation)
time frame: 12-15 weeks post-treatment
description: Cosmetic appearance of treated areas is evaluated by investigators clinically (scores on a scale) using a 4-point scale where 0 = none, 1= acceptable, 2= good and 3= excellent outcome.
measure: Patient-reported Cosmesis
time frame: 12-15 weeks post-treatment
description: Cosmetic appearance is evaluated by patients at the end of the study (scores on a scale) using a 4 point scale where 0 = none, 1= acceptable, 2= good and 3= excellent
measure: Patient Pretreatment Preference
time frame: 12-15 weeks post-treatment
description: Patients were asked to report which pretreatment they preferred: Laser, microdermabrasion, or no preference
arm group label: Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion
arm group type: Experimental
description: WIthin each participant, two 50 cm2 adjacent test areas were randomized to laser or microdermabrasion pretreatment prior to daylight photodynamic therapy.
intervention type: Device
intervention name: Ablative Fractional Carbon Dioxide (CO2) Laser
description: One 50 cm2 test area was randomized to pretreatment using a fractional 2940 nm Er:YAG laser (Joule®; Sciton Inc., Palo Alto, CA, USA). To remove hyperkeratosis, a fully-ablative 4 mm handpiece was optionally applied, followed by a single pass of a fractional Profrax 430 handpiece for all AKs. Subsequent field treatment consisted of a single pass of the Profrax 430 handpiece over the entire test area. Immediately after pretreatment, a 0.5 mm layer of methyl aminolevulinate (Metvix ® cream 16%; Galderma, Paris, France) was applied. After 30 minutes, patients were exposed to 2 hours of ambient daylight, according to approved procedure. After light exposure, cream was wiped off and test areas were covered for the remainder of the day.
arm group label: Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion
intervention type: Device
intervention name: Microdermabrasion
description: Another adjacent 50 cm2 test area was exposed to microdermabrasion using an MD pad with 58.5 µm-diameter particles (Ambu® Skin Prep Pads 2121M; Ambu A/S, Ballerup, Denmark). Lesion-directed treatment consisted of an increasing number of swipes concentrated to AK lesions. During field treatment, multiple swipes were applied in perpendicular directions over the entire test area. Immediately after pretreatment, a 0.5 mm layer of methyl aminolevulinate (Metvix ® cream 16%; Galderma, Paris, France) was applied. After 30 minutes, patients were exposed to 2 hours of ambient daylight, according to approved procedure. After light exposure, cream was wiped off and test areas were covered for the remainder of the day.
arm group label: Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Merete Haedersdal, MD, Dr. Med
role: Principal Investigator
affiliation: Bispebjerg Hospital
responsible party type: Principal Investigator
investigator affiliation: Bispebjerg Hospital
investigator full name: Merete Haedersdal
investigator title: Professor and Senior Physician
mesh term: Keratosis, Actinic
mesh term: Keratosis
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 