<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/NCT01668030</url>
  </required_header>
  <id_info>
    <org_study_id>11.0456</org_study_id>
    <nct_id>NCT01668030</nct_id>
  </id_info>
  <brief_title>Comparison of Wound Bed Establishment in Facial Burns</brief_title>
  <official_title>Comparison of Wound Bed Establishment in Facial Burns Using Two Standard Ointments</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Louisville</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Healthpoint</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Louisville</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Forty percent of patients admitted to the contributing regional burn unit over a five month&#xD;
      period received facial burns (n=14). The purpose of this study is to examine if the time&#xD;
      until a granulation bed is well established can be decreased be using an enzymatic agent,&#xD;
      when compared to a second standard ointment, for patients with partial-thickness facial&#xD;
      burns. The current study will use a prospective, experimental study design in which each&#xD;
      individual will be their own matched control. That is, each individual will receive both the&#xD;
      experimental ointment (one-side of the face) and the standard ointment (other-side of the&#xD;
      face). Outcomes measured will be the benefits (e.g., decreased in the time until granulation&#xD;
      bed establishment) one ointment achieves in partial-thickness facial burns when compared to a&#xD;
      second ointment. Exploratory analyses will examine the relationships among demographic&#xD;
      variables, granulation bed establishment time, pain, anxiety, itching, and scarring. That is,&#xD;
      testing whether the time until granulation establishment may be associated with an&#xD;
      individual's demographic variables, treatment type, pain, anxiety, itching levels, and&#xD;
      scarring. Significance for all analysis will be at the 0.05 level. The investigators&#xD;
      hypothesize that promoting rapid granulation bed establishment will decrease hospital length&#xD;
      of stays, costs, risk of infection, and possibly associated appearance changes. The results&#xD;
      from the current study will provide preliminary findings for a future, more sophisticated&#xD;
      study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rapid wound healing in burn injuries advances wound closure, and decreases opportunities for&#xD;
      infection and scarring (Hansbrough, Achauer, Dawson, et al., 1995; Soroff &amp; Sasvary, 1994);&#xD;
      also leading to a shorter length of stays (LOS). Decreased LOS in the hospital supported by&#xD;
      rapid wound closure facilitates reentry to the home and work environments should lead to a&#xD;
      reduction in the costs associated with hospitalization. In addition, for patients with facial&#xD;
      burns, rapid granulation bed establishment may decrease associated appearance changes.&#xD;
&#xD;
      Use of an enzymatic agent has been described in only three studies (Hansbrough, Achauer,&#xD;
      Dawson, et al., 1995; Soroff &amp; Sasvary, 1994; Varma, Bugatch, &amp; German 1973). Treatment an&#xD;
      enzymatic agent resulted in shorter time to achieve a clean wound bed and significantly more&#xD;
      rapid wound healing when compared to controls or other agents for 94 patients with&#xD;
      non-facial, partial-thickness burns (Hansbrough, Achauer, Dawson, et al.; Soroff &amp; Sasvary).&#xD;
      Twenty patients with dermal ulcers treated with an enzmatic agent, when compared to placebo&#xD;
      controls, showed significantly decreased pus, odor, necrosis, and inflammation (Varma,&#xD;
      Bugatch, &amp; German, 1973). There was a relative reduction in wound size almost reaching&#xD;
      significance (p&lt;0.07) for those patients with dermal ulcers too.&#xD;
&#xD;
      Though an enzymatic agent is without purported antibiotic properties, a rapid reduction in&#xD;
      bacterial burden in wounds has been shown in animal models (Payne, Salas, Ko, Naidu, Donate,&#xD;
      Wright et al., 2008). The bacterial burden decreased rapidly in scald burn wounds to achieve&#xD;
      a bacterial balance for 15 rats with E-coli infected wounds when compared with saline-treated&#xD;
      controls to &lt;105 colony forming units/gram of tissue (p &lt; .05).&#xD;
&#xD;
      Previous studies have suggested that the exploratory variables being collected are associated&#xD;
      with shorter healing times and lower infection rates. Whether these differences are actually&#xD;
      due to some other mediating/moderating factor (gender-specific enzyme or hormone&#xD;
      concentrations, gene interaction, metabolism, etc) and not the exploratory variables is&#xD;
      unclear and not empirically established. A future, larger study will hopefully more fully&#xD;
      explore these relationships. However, to justify the more detailed investigations will&#xD;
      require showing differences at the more crude level. Unfortunately, to date there has been no&#xD;
      research examining the potential benefits of using collagenase in patients with facial burn&#xD;
      injuries. As a result, the aims of this study are to:&#xD;
&#xD;
        1. Show the benefit (e.g., decreased time until the granulation bed is well established,&#xD;
           shorter time until wound closure) an enzymatic agent achieves in partial-thickness&#xD;
           facial burns when compared to a common antibacterial agent;&#xD;
&#xD;
        2. Investigate the interrelationships among demographic variables, treatment, pain,&#xD;
           anxiety, and itch;&#xD;
&#xD;
        3. Explore whether time to granulation bed establishment can be predicted from treatment;&#xD;
           when adjusting for demographic variables, pain, anxiety, and itch levels.&#xD;
&#xD;
        4. Examine the long-term scarring and social experience of persons with facial burns.&#xD;
&#xD;
      Design: A prospective, experimental study design in which each individual will be their own&#xD;
      matched control.&#xD;
&#xD;
      Methods&#xD;
&#xD;
      Procedure. Within 24 hours of burn unit admission, patients or their spouses, or guardians&#xD;
      will be asked regarding study participation. Upon patient agreement, and signing the&#xD;
      institutional review board approved informed consent form, HIPAA Research Authorization, a&#xD;
      demographic information form will be completed and wound culture results obtained (if&#xD;
      ordered).&#xD;
&#xD;
      The patients will be randomized into receiving either bacitracin or collagenase to the right&#xD;
      side of the face (ointment one). Ointment two will be applied to the left side of the face.&#xD;
      Treatment of the partial-thickness facial burns will be performed by the nurses on the burn&#xD;
      unit according to burn unit protocol. Therefore, each person will serve as their own matched&#xD;
      control, thus reducing the sample size required to achieve sufficient power for the study by&#xD;
      reducing deviance between cases and control (i.e., age, pain, itch, size of burn, and&#xD;
      scarring). Also, this type of study design will allow us to achieve valid, reliable results&#xD;
      with fewer individuals. This is a typical study design for similar ointment and eye drops&#xD;
      studies. The bridge of the nose will be used as a guide to divide the face in half&#xD;
      lengthwise. The wound will be cleansed and dressed twice daily. Treatment will continue until&#xD;
      the granulation bed is well established. Daily ratings of pain, anxiety, and itch will be&#xD;
      obtained at each morning dressing change. Digital photographs of only the facial burn will be&#xD;
      taken weekly and at the first outpatient visit.&#xD;
&#xD;
      Patient confidentiality will be maintained by assigning participants a random, unique, study&#xD;
      identification number that cannot be linked directly to any individual. This random number&#xD;
      will be used in all study data sets for data management and data analysis. Signed (approved)&#xD;
      informed consent forms will be kept in a locked file in the principle investigator's office.&#xD;
      The research data sets will be stored on a university secured computer drive.&#xD;
&#xD;
      Digital photographs will be identified by patient number. These photographs will be rated by&#xD;
      burn wound experts recruited from a posting on the American Burn Association web site (e.g.&#xD;
      nurses and/or physical therapists certified in wound care with a minimum of 5 years'&#xD;
      experience). Patients' records will also be assessed weekly as to whether any patient on&#xD;
      study has a wound or blood infection confirmed by a positive laboratory culture. Those&#xD;
      patients with confirmed positive cultures will be dropped from the study. Patient pain,&#xD;
      anxiety, and itch scoring will be obtained and recorded by the nurses caring for patients on&#xD;
      the burn unit.&#xD;
&#xD;
      Assessment of scarring will be obtained at the first out-patient visit by both the healthcare&#xD;
      provider and patient. For the three and six month follow-ups, every effort will be made to&#xD;
      have both the health care provider and patient assessments, however, it may not always be&#xD;
      possible to have the patient return to the hospital (e.g., costs associated with travel and&#xD;
      missing work) so the patient's assessment will be obtained via telephone. Assessment of the&#xD;
      social experience will be obtained by completing the two instruments and open-ended questions&#xD;
      either in-person or through a telephone interview at the first out-patient visit, at three&#xD;
      and six months after injury.&#xD;
&#xD;
      Instrumentation&#xD;
&#xD;
      Pain and Anxiety. Physician ordered analgesic and anxiety therapy will be provided per&#xD;
      patient request prior to each dressing change. At each morning dressing change, patients will&#xD;
      rate their perception of pain and anxiety, separately, with a 10-point visual analogue scale&#xD;
      (where 1= no pain, or anxiety and 10= the most possible) at three time points. These times&#xD;
      will be: prior to cleansing and debridement, at completion of the dressing change, and 30&#xD;
      minutes after treatment. The Richmond Agitation and Sedation Scale (RASS) will be used with&#xD;
      non-verbal patients.&#xD;
&#xD;
      Richmond Agitation and Sedation Scale (RASS). Inter-rater reliability in 290-paired&#xD;
      observations by nurses, results of both the RASS demonstrated excellent inter-rater&#xD;
      reliability (weighted kappa, 0.91 and 0.94, respectively) (Ely, Truman, Shintani, et al.,&#xD;
      2003). Criterion validity was tested in 411-paired observations in the first 96 patients of&#xD;
      the validation cohort, in whom the RAS showed significant differences between levels of&#xD;
      consciousness (P&lt;.001 for all) and correctly identified fluctuations within patients over&#xD;
      time (P&lt;.001). Face validity was demonstrated via a survey of 26 critical care nurses, which&#xD;
      the results showed that 92% agreed or strongly agreed with the RASS scoring scheme, and 81%&#xD;
      agreed or strongly agreed that the instrument provided a consensus for goal-directed delivery&#xD;
      of medications.&#xD;
&#xD;
      Itch. Physician ordered itch therapy (e.g., Benadryl, Atarax, or Claritin) will be provided&#xD;
      per patient request prior to each dressing change. At each morning dressing change, patients&#xD;
      will rate their perception of itch with a 10-point visual analogue scale (where 1=no itch and&#xD;
      10=the most possible), at three time points. These times will be: prior to cleansing and&#xD;
      debridement, at completion of the dressing change, and 30 minutes after treatment.&#xD;
&#xD;
      Scarring. Scarring will be measured by two instruments [The Patient and Observer Scar&#xD;
      Assessment Scale (POSAS)] developed by Draaijers, Tempelman, Botman, et al. (2004) and&#xD;
      further tested by Van de kar, Corion, Smeulders, et al. (2005. These two instruments, one for&#xD;
      the health care provider and the second for the patient, recognizes the need for both the&#xD;
      professional's and patient-based need for scar assessment, whereas, the Vancouver Scar Scale&#xD;
      (VSS) only assesses scar severity from the professional's viewpoint. Though the VSS has been&#xD;
      accepted and used as a scar assessment tool, there is not evidence to suggest it is the &quot;gold&#xD;
      standard&quot; measure of burns scarring, and additionally, it does not include the patient's&#xD;
      perception of their scarring.&#xD;
&#xD;
      The POSAS has items assessing vascularity, pigmentation, thickness, relief and pliability,&#xD;
      rated on a 10-point numeric scale, with normal skin and worst scar used as end labels. Items&#xD;
      on the patient scale directly correspond to theses except for scar color. Patients are asked&#xD;
      to rate their itchiness and scar pain. A ten-point numeric scale is used (1=no complaints&#xD;
      /normal skin, 10=worst imaginable/very different). Individual items are summed with higher&#xD;
      scores representing poorer scars and lower scores representing scars more closely to normal&#xD;
      skin. Both scales showed acceptable internal consistency (Cronbach's alpha 0.76 (patient) and&#xD;
      0.69 (observer). The test-retest reliability of the patient scale has not been evaluated in&#xD;
      burn scars.&#xD;
&#xD;
      Social Experience. It is proposed that partial-thickness burns to both sides of the face&#xD;
      result in non-normal appearance which may cause stigmatizing and dehumanizing behavior&#xD;
      directed at these burn survivors (Lawrence, Fauerbach, Heinberg, Doctor, and Thombs, 2006;&#xD;
      Lawrence, Rosenberg, Rimmer, Tombs, and Fauerbach, 2010). The following two instruments will&#xD;
      assess the social experience.&#xD;
&#xD;
      The social experience will be measured by two instruments: the Perceived Stigmatization&#xD;
      Questionnaire (PSQ) and the Social Comfort Questionnaire (SCQ) (Lawrence, Fauerbach,&#xD;
      Heinberg, Doctor, and Thombs, 2006; Lawrence, Rosenberg, Rimmer, Tombs, and Fauerbach, 2010).&#xD;
      Both instruments were developed and tested for use with a population of burn injury&#xD;
      survivors. The PQS is a 21 item scale where each item is measured on a 5-point Likert scale&#xD;
      (never, almost never, sometimes, often, always). Three factors were loaded: absence of&#xD;
      friendly behavior, confused behavior and starring, and hostile behavior. Scores are&#xD;
      calculated by totaling items and dividing by 21. Higher scores indicate levels of perceived&#xD;
      stigmatizing behaviors.&#xD;
&#xD;
      The SCQ is an eight item, one factor scale. Each item is also measured on a 5-point Likert&#xD;
      scale (never, almost never, sometimes, often, always). The final score is the average of&#xD;
      items; higher scores indicate higher social comfort.&#xD;
&#xD;
      Open-ended Questions: Several open-ended questions will be included to allow participants to&#xD;
      describe instances of how their social experience changed after the facial burn injury. It is&#xD;
      hoped that these answers will further clarify the two instrument findings&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2012</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">November 2013</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    <masking_description>Participants received both the test drug and the standard of care, one on each side of the face.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Time to Wound Epithelialization</measure>
    <time_frame>Two years</time_frame>
    <description>Time it required the subjects treated with two standard ointments to establish a wound bed.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Burns</condition>
  <arm_group>
    <arm_group_label>Bacitracin on left, Enzymatic agent on right</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects were randomized to receive enzymatic agent on right side of face and bacitracin on left.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Bacitractin on right, enzymatic agent on left</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects were randomized to receive enzymatic agent on left side of face and bacitracin on right.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enzymatic agent</intervention_name>
    <description>Enzymatic agent</description>
    <arm_group_label>Bacitracin on left, Enzymatic agent on right</arm_group_label>
    <arm_group_label>Bacitractin on right, enzymatic agent on left</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bacitracin</intervention_name>
    <arm_group_label>Bacitracin on left, Enzymatic agent on right</arm_group_label>
    <arm_group_label>Bacitractin on right, enzymatic agent on left</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients (over the age of 18 years) admitted to the burn unit with a minimum of 1%&#xD;
             partial-thickness burns each side of the face.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients with superficial or full-thickness facial burns;&#xD;
&#xD;
          -  patients receiving facial grafts; patients with burns from chemical or contact&#xD;
             sources;&#xD;
&#xD;
          -  patients with wound infection;&#xD;
&#xD;
          -  any patients starting treatment 24 hours after burn injury;&#xD;
&#xD;
          -  patients with known sensitivity to either standard treatment; and&#xD;
&#xD;
          -  any women by history who are pregnant or breast feeding.&#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>Carlee R. Lehna, PhD, APRN-BC</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Louisville, School of Nursing</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UofL Health Care</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>August 8, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <results_first_submitted>April 5, 2017</results_first_submitted>
  <results_first_submitted_qc>July 27, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">August 28, 2017</results_first_posted>
  <last_update_submitted>July 27, 2017</last_update_submitted>
  <last_update_submitted_qc>July 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Facial</keyword>
  <keyword>Partial thickness</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Burns</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bacitracin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Patients were recruited from hospital burn unit.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Bacitracin Treated Side of Face</title>
          <description>Bacitractin was applied to one side of face.</description>
        </group>
        <group group_id="P2">
          <title>Enzymatic Agent Treatment Side of Face</title>
          <description>Enzymatic agent applied to cheek</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </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>All Study Participants</title>
          <description>Double Blind (masked to subject, caregiver, &amp; outcome assessor. Intervention is that either drug is randomized into being applied to either right or left side of face.&#xD;
Enzymatic treatment versus Bacitracin: Person is their own control. Ointments randomly applied to either side of face.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <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="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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 States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Time to Wound Epithelialization</title>
        <description>Time it required the subjects treated with two standard ointments to establish a wound bed.</description>
        <time_frame>Two years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bacitracin Treated Side of Face</title>
            <description>Double Blind (masked to subject, caregiver, &amp; outcome assessor. Intervention is that either drug is randomized into being applied to either right or left side of face.&#xD;
Enzymatic agent versus Bacitracin: Person is their own control. Ointments randomly applied to either side of face.</description>
          </group>
          <group group_id="O2">
            <title>Enzymatic Agent Treatment Side of Face</title>
            <description>Double Blind (masked to subject, caregiver, &amp; outcome assessor. Intervention is that either drug is randomized into being applied to either right or left side of face.&#xD;
Enzymatic agent versus Bacitracin: Person is their own control. Ointments randomly applied to either side of face.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Wound Epithelialization</title>
          <description>Time it required the subjects treated with two standard ointments to establish a wound bed.</description>
          <units>days</units>
          <param>Number</param>
          <units_analyzed>cheeks (side of face)</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>cheeks (side of face)</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.4"/>
                    <measurement group_id="O2" value="37.6"/>
                  </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</non_inferiority_type>
            <p_value>.0853</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>All Study Participants</title>
          <description>Double Blind (masked to subject, caregiver, &amp; outcome assessor. Intervention is that either drug is randomized into being applied to either right or left side of face.&#xD;
Enzymatic treatment versus Bacitracin: Person is their own control. Ointments randomly applied to either side of face.</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="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Small sample size. The study did not differentiate between deep partial thickness and superficial partial thickness burns. another way to trial this study methodology would be to use animal subjects.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Carlee Lehna, Associate Professor</name_or_title>
      <organization>University of Louisville School of Nursing</organization>
      <phone>502-852-3913</phone>
      <email>carlee.lehna@louisville.edu</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/NCT01668030
org study id: 11.0456
nct id: NCT01668030
lead sponsor: 
collaborator: 
has dmc: No
Forty percent of patients admitted to the contributing regional burn unit over a five month
      period received facial burns (n=14). The purpose of this study is to examine if the time
      until a granulation bed is well established can be decreased be using an enzymatic agent,
      when compared to a second standard ointment, for patients with partial-thickness facial
      burns. The current study will use a prospective, experimental study design in which each
      individual will be their own matched control. That is, each individual will receive both the
      experimental ointment (one-side of the face) and the standard ointment (other-side of the
      face). Outcomes measured will be the benefits (e.g., decreased in the time until granulation
      bed establishment) one ointment achieves in partial-thickness facial burns when compared to a
      second ointment. Exploratory analyses will examine the relationships among demographic
      variables, granulation bed establishment time, pain, anxiety, itching, and scarring. That is,
      testing whether the time until granulation establishment may be associated with an
      individual's demographic variables, treatment type, pain, anxiety, itching levels, and
      scarring. Significance for all analysis will be at the 0.05 level. The investigators
      hypothesize that promoting rapid granulation bed establishment will decrease hospital length
      of stays, costs, risk of infection, and possibly associated appearance changes. The results
      from the current study will provide preliminary findings for a future, more sophisticated
      study.
Rapid wound healing in burn injuries advances wound closure, and decreases opportunities for
      infection and scarring (Hansbrough, Achauer, Dawson, et al., 1995; Soroff & Sasvary, 1994);
      also leading to a shorter length of stays (LOS). Decreased LOS in the hospital supported by
      rapid wound closure facilitates reentry to the home and work environments should lead to a
      reduction in the costs associated with hospitalization. In addition, for patients with facial
      burns, rapid granulation bed establishment may decrease associated appearance changes.

      Use of an enzymatic agent has been described in only three studies (Hansbrough, Achauer,
      Dawson, et al., 1995; Soroff & Sasvary, 1994; Varma, Bugatch, & German 1973). Treatment an
      enzymatic agent resulted in shorter time to achieve a clean wound bed and significantly more
      rapid wound healing when compared to controls or other agents for 94 patients with
      non-facial, partial-thickness burns (Hansbrough, Achauer, Dawson, et al.; Soroff & Sasvary).
      Twenty patients with dermal ulcers treated with an enzmatic agent, when compared to placebo
      controls, showed significantly decreased pus, odor, necrosis, and inflammation (Varma,
      Bugatch, & German, 1973). There was a relative reduction in wound size almost reaching
      significance (p<0.07) for those patients with dermal ulcers too.

      Though an enzymatic agent is without purported antibiotic properties, a rapid reduction in
      bacterial burden in wounds has been shown in animal models (Payne, Salas, Ko, Naidu, Donate,
      Wright et al., 2008). The bacterial burden decreased rapidly in scald burn wounds to achieve
      a bacterial balance for 15 rats with E-coli infected wounds when compared with saline-treated
      controls to <105 colony forming units/gram of tissue (p < .05).

      Previous studies have suggested that the exploratory variables being collected are associated
      with shorter healing times and lower infection rates. Whether these differences are actually
      due to some other mediating/moderating factor (gender-specific enzyme or hormone
      concentrations, gene interaction, metabolism, etc) and not the exploratory variables is
      unclear and not empirically established. A future, larger study will hopefully more fully
      explore these relationships. However, to justify the more detailed investigations will
      require showing differences at the more crude level. Unfortunately, to date there has been no
      research examining the potential benefits of using collagenase in patients with facial burn
      injuries. As a result, the aims of this study are to:

        1. Show the benefit (e.g., decreased time until the granulation bed is well established,
           shorter time until wound closure) an enzymatic agent achieves in partial-thickness
           facial burns when compared to a common antibacterial agent;

        2. Investigate the interrelationships among demographic variables, treatment, pain,
           anxiety, and itch;

        3. Explore whether time to granulation bed establishment can be predicted from treatment;
           when adjusting for demographic variables, pain, anxiety, and itch levels.

        4. Examine the long-term scarring and social experience of persons with facial burns.

      Design: A prospective, experimental study design in which each individual will be their own
      matched control.

      Methods

      Procedure. Within 24 hours of burn unit admission, patients or their spouses, or guardians
      will be asked regarding study participation. Upon patient agreement, and signing the
      institutional review board approved informed consent form, HIPAA Research Authorization, a
      demographic information form will be completed and wound culture results obtained (if
      ordered).

      The patients will be randomized into receiving either bacitracin or collagenase to the right
      side of the face (ointment one). Ointment two will be applied to the left side of the face.
      Treatment of the partial-thickness facial burns will be performed by the nurses on the burn
      unit according to burn unit protocol. Therefore, each person will serve as their own matched
      control, thus reducing the sample size required to achieve sufficient power for the study by
      reducing deviance between cases and control (i.e., age, pain, itch, size of burn, and
      scarring). Also, this type of study design will allow us to achieve valid, reliable results
      with fewer individuals. This is a typical study design for similar ointment and eye drops
      studies. The bridge of the nose will be used as a guide to divide the face in half
      lengthwise. The wound will be cleansed and dressed twice daily. Treatment will continue until
      the granulation bed is well established. Daily ratings of pain, anxiety, and itch will be
      obtained at each morning dressing change. Digital photographs of only the facial burn will be
      taken weekly and at the first outpatient visit.

      Patient confidentiality will be maintained by assigning participants a random, unique, study
      identification number that cannot be linked directly to any individual. This random number
      will be used in all study data sets for data management and data analysis. Signed (approved)
      informed consent forms will be kept in a locked file in the principle investigator's office.
      The research data sets will be stored on a university secured computer drive.

      Digital photographs will be identified by patient number. These photographs will be rated by
      burn wound experts recruited from a posting on the American Burn Association web site (e.g.
      nurses and/or physical therapists certified in wound care with a minimum of 5 years'
      experience). Patients' records will also be assessed weekly as to whether any patient on
      study has a wound or blood infection confirmed by a positive laboratory culture. Those
      patients with confirmed positive cultures will be dropped from the study. Patient pain,
      anxiety, and itch scoring will be obtained and recorded by the nurses caring for patients on
      the burn unit.

      Assessment of scarring will be obtained at the first out-patient visit by both the healthcare
      provider and patient. For the three and six month follow-ups, every effort will be made to
      have both the health care provider and patient assessments, however, it may not always be
      possible to have the patient return to the hospital (e.g., costs associated with travel and
      missing work) so the patient's assessment will be obtained via telephone. Assessment of the
      social experience will be obtained by completing the two instruments and open-ended questions
      either in-person or through a telephone interview at the first out-patient visit, at three
      and six months after injury.

      Instrumentation

      Pain and Anxiety. Physician ordered analgesic and anxiety therapy will be provided per
      patient request prior to each dressing change. At each morning dressing change, patients will
      rate their perception of pain and anxiety, separately, with a 10-point visual analogue scale
      (where 1= no pain, or anxiety and 10= the most possible) at three time points. These times
      will be: prior to cleansing and debridement, at completion of the dressing change, and 30
      minutes after treatment. The Richmond Agitation and Sedation Scale (RASS) will be used with
      non-verbal patients.

      Richmond Agitation and Sedation Scale (RASS). Inter-rater reliability in 290-paired
      observations by nurses, results of both the RASS demonstrated excellent inter-rater
      reliability (weighted kappa, 0.91 and 0.94, respectively) (Ely, Truman, Shintani, et al.,
      2003). Criterion validity was tested in 411-paired observations in the first 96 patients of
      the validation cohort, in whom the RAS showed significant differences between levels of
      consciousness (P<.001 for all) and correctly identified fluctuations within patients over
      time (P<.001). Face validity was demonstrated via a survey of 26 critical care nurses, which
      the results showed that 92% agreed or strongly agreed with the RASS scoring scheme, and 81%
      agreed or strongly agreed that the instrument provided a consensus for goal-directed delivery
      of medications.

      Itch. Physician ordered itch therapy (e.g., Benadryl, Atarax, or Claritin) will be provided
      per patient request prior to each dressing change. At each morning dressing change, patients
      will rate their perception of itch with a 10-point visual analogue scale (where 1=no itch and
      10=the most possible), at three time points. These times will be: prior to cleansing and
      debridement, at completion of the dressing change, and 30 minutes after treatment.

      Scarring. Scarring will be measured by two instruments [The Patient and Observer Scar
      Assessment Scale (POSAS)] developed by Draaijers, Tempelman, Botman, et al. (2004) and
      further tested by Van de kar, Corion, Smeulders, et al. (2005. These two instruments, one for
      the health care provider and the second for the patient, recognizes the need for both the
      professional's and patient-based need for scar assessment, whereas, the Vancouver Scar Scale
      (VSS) only assesses scar severity from the professional's viewpoint. Though the VSS has been
      accepted and used as a scar assessment tool, there is not evidence to suggest it is the "gold
      standard" measure of burns scarring, and additionally, it does not include the patient's
      perception of their scarring.

      The POSAS has items assessing vascularity, pigmentation, thickness, relief and pliability,
      rated on a 10-point numeric scale, with normal skin and worst scar used as end labels. Items
      on the patient scale directly correspond to theses except for scar color. Patients are asked
      to rate their itchiness and scar pain. A ten-point numeric scale is used (1=no complaints
      /normal skin, 10=worst imaginable/very different). Individual items are summed with higher
      scores representing poorer scars and lower scores representing scars more closely to normal
      skin. Both scales showed acceptable internal consistency (Cronbach's alpha 0.76 (patient) and
      0.69 (observer). The test-retest reliability of the patient scale has not been evaluated in
      burn scars.

      Social Experience. It is proposed that partial-thickness burns to both sides of the face
      result in non-normal appearance which may cause stigmatizing and dehumanizing behavior
      directed at these burn survivors (Lawrence, Fauerbach, Heinberg, Doctor, and Thombs, 2006;
      Lawrence, Rosenberg, Rimmer, Tombs, and Fauerbach, 2010). The following two instruments will
      assess the social experience.

      The social experience will be measured by two instruments: the Perceived Stigmatization
      Questionnaire (PSQ) and the Social Comfort Questionnaire (SCQ) (Lawrence, Fauerbach,
      Heinberg, Doctor, and Thombs, 2006; Lawrence, Rosenberg, Rimmer, Tombs, and Fauerbach, 2010).
      Both instruments were developed and tested for use with a population of burn injury
      survivors. The PQS is a 21 item scale where each item is measured on a 5-point Likert scale
      (never, almost never, sometimes, often, always). Three factors were loaded: absence of
      friendly behavior, confused behavior and starring, and hostile behavior. Scores are
      calculated by totaling items and dividing by 21. Higher scores indicate levels of perceived
      stigmatizing behaviors.

      The SCQ is an eight item, one factor scale. Each item is also measured on a 5-point Likert
      scale (never, almost never, sometimes, often, always). The final score is the average of
      items; higher scores indicate higher social comfort.

      Open-ended Questions: Several open-ended questions will be included to allow participants to
      describe instances of how their social experience changed after the facial burn injury. It is
      hoped that these answers will further clarify the two instrument findings
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
masking description: Participants received both the test drug and the standard of care, one on each side of the face.
measure: Time to Wound Epithelialization
time frame: Two years
description: Time it required the subjects treated with two standard ointments to establish a wound bed.
arm group label: Bacitracin on left, Enzymatic agent on right
arm group type: Experimental
description: Subjects were randomized to receive enzymatic agent on right side of face and bacitracin on left.
arm group label: Bacitractin on right, enzymatic agent on left
arm group type: Experimental
description: Subjects were randomized to receive enzymatic agent on left side of face and bacitracin on right.
intervention type: Drug
intervention name: Enzymatic agent
description: Enzymatic agent
arm group label: Bacitracin on left, Enzymatic agent on right
arm group label: Bacitractin on right, enzymatic agent on left
intervention type: Drug
intervention name: Bacitracin
arm group label: Bacitracin on left, Enzymatic agent on right
arm group label: Bacitractin on right, enzymatic agent on left
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Carlee R. Lehna, PhD, APRN-BC
role: Principal Investigator
affiliation: University of Louisville, School of Nursing
facility: 
country: United States
responsible party type: Sponsor
mesh term: Burns
mesh term: Bacitracin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Small sample size. The study did not differentiate between deep partial thickness and superficial partial thickness burns. another way to trial this study methodology would be to use animal subjects.
point of contact: 