<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/NCT02247193</url>
  </required_header>
  <id_info>
    <org_study_id>HSC-MS-14-0335</org_study_id>
    <nct_id>NCT02247193</nct_id>
  </id_info>
  <brief_title>Botulinum Toxin to Improve Cosmesis of Primary Cleft Lip Repair</brief_title>
  <official_title>Botulinum Toxin to Improve Cosmesis of Primary Cleft Lip Repair</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Health Science Center, Houston</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Texas Health Science Center, Houston</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Objective: To determine if the use of botulinum toxin during primary cleft lip repair&#xD;
      improves the cosmetic appearance of the cleft lip scar&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2015</start_date>
  <completion_date type="Actual">January 13, 2020</completion_date>
  <primary_completion_date type="Actual">January 13, 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Blinded Plastic Surgeons</measure>
    <time_frame>6 months</time_frame>
    <description>The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Blinded Plastic Surgeons</measure>
    <time_frame>12 months</time_frame>
    <description>The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Blinded Plastic Surgeons</measure>
    <time_frame>6 months</time_frame>
    <description>The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Blinded Plastic Surgeons</measure>
    <time_frame>12 months</time_frame>
    <description>The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Crowdsourced Raters</measure>
    <time_frame>6 months</time_frame>
    <description>The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Crowdsourced Raters</measure>
    <time_frame>12 months</time_frame>
    <description>The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Crowdsourced Raters</measure>
    <time_frame>6 months</time_frame>
    <description>The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Crowdsourced Raters</measure>
    <time_frame>12 months</time_frame>
    <description>The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Cleft Lip</condition>
  <condition>Scarring</condition>
  <condition>Cleft Palate</condition>
  <arm_group>
    <arm_group_label>Botulinum Toxin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Injection of botulinum toxin into cleft lip at time of surgical repair.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Injection of normal saline into cleft lip at time of surgical repair.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Botulinum Toxin Type A</intervention_name>
    <description>Injection of botulinum toxin at the time of surgery at cleft lip repair site. Botulinum toxin will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
    <arm_group_label>Botulinum Toxin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal Saline Injection</intervention_name>
    <description>Injection of normal saline into cleft lip at time of surgical repair. Saline will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
    <arm_group_label>Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  complete unilateral cleft lip with or without cleft palate&#xD;
&#xD;
          -  planned for a primary cleft lip repair&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -bilateral cleft lip&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>6 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jaecel O Shah, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UTHealth</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memorial Hermann Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Pascual-Pascual SI, Pascual-Castroviejo I. Safety of botulinum toxin type A in children younger than 2 years. Eur J Paediatr Neurol. 2009 Nov;13(6):511-5. doi: 10.1016/j.ejpn.2008.10.006. Epub 2008 Nov 25.</citation>
    <PMID>19036619</PMID>
  </reference>
  <reference>
    <citation>Galarraga IM. Use of botulinum toxin in cheiloplasty: A new method to decrease tension. Can J Plast Surg. 2009 Fall;17(3):e1-2. doi: 10.1177/229255030901700313.</citation>
    <PMID>20808741</PMID>
  </reference>
  <reference>
    <citation>Alvarez CM, De Vera MA, Chhina H, Williams L, Durlacher K, Kaga S. The use of botulinum type A toxin in the treatment of idiopathic clubfoot: 5-year follow-up. J Pediatr Orthop. 2009 Sep;29(6):570-5. doi: 10.1097/BPO.0b013e3181b2b3d4.</citation>
    <PMID>19700985</PMID>
  </reference>
  <reference>
    <citation>Gassner HG, Sherris DA, Friedman O. Botulinum toxin-induced immobilization of lower facial wounds. Arch Facial Plast Surg. 2009 Mar-Apr;11(2):140-2. doi: 10.1001/archfacial.2009.3. No abstract available.</citation>
    <PMID>19289689</PMID>
  </reference>
  <reference>
    <citation>Christiansen G, Mohney BG, Baratz KH, Bradley EA. Botulinum toxin for the treatment of congenital entropion. Am J Ophthalmol. 2004 Jul;138(1):153-5. doi: 10.1016/j.ajo.2004.02.023.</citation>
    <PMID>15234303</PMID>
  </reference>
  <reference>
    <citation>Sherris DA, Gassner HG. Botulinum toxin to minimize facial scarring. Facial Plast Surg. 2002 Feb;18(1):35-9. doi: 10.1055/s-2002-19825.</citation>
    <PMID>11823931</PMID>
  </reference>
  <reference>
    <citation>Sykes JM. Management of the cleft lip deformity. Facial Plast Surg Clin North Am. 2001 Feb;9(1):37-50.</citation>
    <PMID>11465005</PMID>
  </reference>
  <reference>
    <citation>Seibert RW. Bilateral cleft nasal repair. Facial Plast Surg. 2000;16(1):69-78. doi: 10.1055/s-2000-7328.</citation>
    <PMID>11802349</PMID>
  </reference>
  <reference>
    <citation>Millard DR Jr. Embryonic rationale for the primary correction of classical congenital clefts of the lip and palate. Ann R Coll Surg Engl. 1994 May;76(3):150-60.</citation>
    <PMID>8017808</PMID>
  </reference>
  <reference>
    <citation>Witt PD, Hardesty RA. Rotation-advancement repair of the unilateral cleft lip. One center's perspective. Clin Plast Surg. 1993 Oct;20(4):633-45.</citation>
    <PMID>8275629</PMID>
  </reference>
  <reference>
    <citation>Lee JS, Lee KB, Lee YR, Choi YN, Park CW, Park SD, Jung DH, Lee CS. Botulinum Toxin Treatment on Upper Limb Function in School Age Children With Bilateral Spastic Cerebral Palsy: One Year Follow-up. Ann Rehabil Med. 2013 Jun;37(3):328-35. doi: 10.5535/arm.2013.37.3.328. Epub 2013 Jun 30.</citation>
    <PMID>23869330</PMID>
  </reference>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 23, 2014</study_first_posted>
  <results_first_submitted>May 17, 2021</results_first_submitted>
  <results_first_submitted_qc>October 5, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 3, 2021</results_first_posted>
  <last_update_submitted>October 5, 2021</last_update_submitted>
  <last_update_submitted_qc>October 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Texas Health Science Center, Houston</investigator_affiliation>
    <investigator_full_name>Matthew Greives</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Botulinum Toxin</keyword>
  <keyword>Botox</keyword>
  <keyword>Craniofacial deformity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cleft Palate</mesh_term>
    <mesh_term>Cleft Lip</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Botulinum Toxins</mesh_term>
    <mesh_term>Botulinum Toxins, Type A</mesh_term>
    <mesh_term>abobotulinumtoxinA</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 17, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT02247193/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Botulinum Toxin</title>
          <description>Injection of botulinum toxin into cleft lip at time of surgical repair.&#xD;
Botulinum Toxin Type A: Injection of botulinum toxin at the time of surgery at cleft lip repair site. Botulinum toxin will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
        </group>
        <group group_id="P2">
          <title>Saline</title>
          <description>Injection of normal saline into cleft lip at time of surgical repair.&#xD;
Normal Saline Injection: Injection of normal saline into cleft lip at time of surgical repair. Saline will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Number Who Underwent Cleft Lip Repair Surgery</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Number Who Received Botox or Placebo</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Number Who Completed the 6-month Follow up</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Number Who Completed the 12-month Follow up</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
              </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>Botulinum Toxin</title>
          <description>Injection of botulinum toxin into cleft lip at time of surgical repair.&#xD;
Botulinum Toxin Type A: Injection of botulinum toxin at the time of surgery at cleft lip repair site. Botulinum toxin will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
        </group>
        <group group_id="B2">
          <title>Saline</title>
          <description>Injection of normal saline into cleft lip at time of surgical repair.&#xD;
Normal Saline Injection: Injection of normal saline into cleft lip at time of surgical repair. Saline will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="30"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="129.53" spread="27.27"/>
                    <measurement group_id="B2" value="135.67" spread="17.41"/>
                    <measurement group_id="B3" value="132.6" spread="22.7"/>
                  </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="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Caucasian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Participants with Syndromic Cleft Lip</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Participants with Presurgical Nasoalveolar Molding (PNAM)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Participants with Complete Cleft Lip</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Participants with Unilateral Cleft Lip</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Participants with Cleft Palate</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Blinded Plastic Surgeons</title>
        <description>The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.</description>
        <time_frame>6 months</time_frame>
        <population>Only 9 in the Botulinum Toxin arm and 11 in the Saline arm were analyzed for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Botulinum Toxin</title>
            <description>Injection of botulinum toxin into cleft lip at time of surgical repair.&#xD;
Botulinum Toxin Type A: Injection of botulinum toxin at the time of surgery at cleft lip repair site. Botulinum toxin will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Injection of normal saline into cleft lip at time of surgical repair.&#xD;
Normal Saline Injection: Injection of normal saline into cleft lip at time of surgical repair. Saline will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
        </group_list>
        <measure>
          <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Blinded Plastic Surgeons</title>
          <description>The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.</description>
          <population>Only 9 in the Botulinum Toxin arm and 11 in the Saline arm were analyzed for this outcome measure.</population>
          <units>score 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="9"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="7" upper_limit="10"/>
                    <measurement group_id="O2" value="9" lower_limit="8" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Blinded Plastic Surgeons</title>
        <description>The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.</description>
        <time_frame>12 months</time_frame>
        <population>Only 9 in the Botulinum Toxin arm and 11 in the Saline arm were analyzed for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Botulinum Toxin</title>
            <description>Injection of botulinum toxin into cleft lip at time of surgical repair.&#xD;
Botulinum Toxin Type A: Injection of botulinum toxin at the time of surgery at cleft lip repair site. Botulinum toxin will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Injection of normal saline into cleft lip at time of surgical repair.&#xD;
Normal Saline Injection: Injection of normal saline into cleft lip at time of surgical repair. Saline will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
        </group_list>
        <measure>
          <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Blinded Plastic Surgeons</title>
          <description>The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.</description>
          <population>Only 9 in the Botulinum Toxin arm and 11 in the Saline arm were analyzed for this outcome measure.</population>
          <units>score 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="9"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="6.5" upper_limit="7"/>
                    <measurement group_id="O2" value="9" lower_limit="6.5" upper_limit="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Blinded Plastic Surgeons</title>
        <description>The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.</description>
        <time_frame>6 months</time_frame>
        <population>Only 9 in the Botulinum Toxin arm and 11 in the Saline arm were analyzed for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Botulinum Toxin</title>
            <description>Injection of botulinum toxin into cleft lip at time of surgical repair.&#xD;
Botulinum Toxin Type A: Injection of botulinum toxin at the time of surgery at cleft lip repair site. Botulinum toxin will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Injection of normal saline into cleft lip at time of surgical repair.&#xD;
Normal Saline Injection: Injection of normal saline into cleft lip at time of surgical repair. Saline will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
        </group_list>
        <measure>
          <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Blinded Plastic Surgeons</title>
          <description>The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.</description>
          <population>Only 9 in the Botulinum Toxin arm and 11 in the Saline arm were analyzed for this outcome measure.</population>
          <units>score 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="9"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="6.0" upper_limit="8.0"/>
                    <measurement group_id="O2" value="8" lower_limit="6.0" upper_limit="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Blinded Plastic Surgeons</title>
        <description>The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.</description>
        <time_frame>12 months</time_frame>
        <population>Only 9 in the Botulinum Toxin arm and 11 in the Saline arm were analyzed for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Botulinum Toxin</title>
            <description>Injection of botulinum toxin into cleft lip at time of surgical repair.&#xD;
Botulinum Toxin Type A: Injection of botulinum toxin at the time of surgery at cleft lip repair site. Botulinum toxin will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Injection of normal saline into cleft lip at time of surgical repair.&#xD;
Normal Saline Injection: Injection of normal saline into cleft lip at time of surgical repair. Saline will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
        </group_list>
        <measure>
          <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Blinded Plastic Surgeons</title>
          <description>The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.</description>
          <population>Only 9 in the Botulinum Toxin arm and 11 in the Saline arm were analyzed for this outcome measure.</population>
          <units>score 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="9"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6" lower_limit="6.0" upper_limit="7.0"/>
                    <measurement group_id="O2" value="7" lower_limit="6.5" upper_limit="7.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Crowdsourced Raters</title>
        <description>The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.</description>
        <time_frame>6 months</time_frame>
        <population>Only 9 in the Botulinum Toxin arm and 11 in the Saline arm were analyzed for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Botulinum Toxin</title>
            <description>Injection of botulinum toxin into cleft lip at time of surgical repair.&#xD;
Botulinum Toxin Type A: Injection of botulinum toxin at the time of surgery at cleft lip repair site. Botulinum toxin will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Injection of normal saline into cleft lip at time of surgical repair.&#xD;
Normal Saline Injection: Injection of normal saline into cleft lip at time of surgical repair. Saline will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
        </group_list>
        <measure>
          <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Crowdsourced Raters</title>
          <description>The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.</description>
          <population>Only 9 in the Botulinum Toxin arm and 11 in the Saline arm were analyzed for this outcome measure.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.40" spread="0.74"/>
                    <measurement group_id="O2" value="8.29" spread="0.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Crowdsourced Raters</title>
        <description>The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.</description>
        <time_frame>12 months</time_frame>
        <population>Only 8 in the Botulinum Toxin arm and 12 in the Saline arm were analyzed for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Botulinum Toxin</title>
            <description>Injection of botulinum toxin into cleft lip at time of surgical repair.&#xD;
Botulinum Toxin Type A: Injection of botulinum toxin at the time of surgery at cleft lip repair site. Botulinum toxin will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Injection of normal saline into cleft lip at time of surgical repair.&#xD;
Normal Saline Injection: Injection of normal saline into cleft lip at time of surgical repair. Saline will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
        </group_list>
        <measure>
          <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Crowdsourced Raters</title>
          <description>The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.</description>
          <population>Only 8 in the Botulinum Toxin arm and 12 in the Saline arm were analyzed for this outcome measure.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.48" spread="0.78"/>
                    <measurement group_id="O2" value="7.72" spread="0.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Crowdsourced Raters</title>
        <description>The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.</description>
        <time_frame>6 months</time_frame>
        <population>Only 9 in the Botulinum Toxin arm and 11 in the Saline arm were analyzed for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Botulinum Toxin</title>
            <description>Injection of botulinum toxin into cleft lip at time of surgical repair.&#xD;
Botulinum Toxin Type A: Injection of botulinum toxin at the time of surgery at cleft lip repair site. Botulinum toxin will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Injection of normal saline into cleft lip at time of surgical repair.&#xD;
Normal Saline Injection: Injection of normal saline into cleft lip at time of surgical repair. Saline will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
        </group_list>
        <measure>
          <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Crowdsourced Raters</title>
          <description>The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.</description>
          <population>Only 9 in the Botulinum Toxin arm and 11 in the Saline arm were analyzed for this outcome measure.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.96" spread="0.74"/>
                    <measurement group_id="O2" value="6.74" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Crowdsourced Raters</title>
        <description>The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.</description>
        <time_frame>12 months</time_frame>
        <population>Only 8 in the Botulinum Toxin arm and 12 in the Saline arm were analyzed for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Botulinum Toxin</title>
            <description>Injection of botulinum toxin into cleft lip at time of surgical repair.&#xD;
Botulinum Toxin Type A: Injection of botulinum toxin at the time of surgery at cleft lip repair site. Botulinum toxin will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
          <group group_id="O2">
            <title>Saline</title>
            <description>Injection of normal saline into cleft lip at time of surgical repair.&#xD;
Normal Saline Injection: Injection of normal saline into cleft lip at time of surgical repair. Saline will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
          </group>
        </group_list>
        <measure>
          <title>Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Crowdsourced Raters</title>
          <description>The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.</description>
          <population>Only 8 in the Botulinum Toxin arm and 12 in the Saline arm were analyzed for this outcome measure.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.01" spread="0.75"/>
                    <measurement group_id="O2" value="6.19" spread="0.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Botulinum Toxin</title>
          <description>Injection of botulinum toxin into cleft lip at time of surgical repair.&#xD;
Botulinum Toxin Type A: Injection of botulinum toxin at the time of surgery at cleft lip repair site. Botulinum toxin will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</description>
        </group>
        <group group_id="E2">
          <title>Saline</title>
          <description>Injection of normal saline into cleft lip at time of surgical repair.&#xD;
Normal Saline Injection: Injection of normal saline into cleft lip at time of surgical repair. Saline will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.</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="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
              </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="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Small sample size; inconsistency in acquiring post-op photos for some; 12 month analysis may be skewed by Botox's short duration of action; crowdsourced raters were not a generalized sample of the population</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Matthew R. Greives, MD</name_or_title>
      <organization>The University of Texas Health Science Center at Houston</organization>
      <phone>713-500-7275</phone>
      <email>Matthew.R.Greives@uth.tmc.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/NCT02247193
org study id: HSC-MS-14-0335
nct id: NCT02247193
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Objective: To determine if the use of botulinum toxin during primary cleft lip repair
      improves the cosmetic appearance of the cleft lip scar
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Blinded Plastic Surgeons
time frame: 6 months
description: The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.
measure: Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Blinded Plastic Surgeons
time frame: 12 months
description: The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.
measure: Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Blinded Plastic Surgeons
time frame: 6 months
description: The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.
measure: Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Blinded Plastic Surgeons
time frame: 12 months
description: The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by three blinded plastic surgeons, who evaluated frontal and basal photographs of participants. The median of the three surgeon scores per participant was first calculated, and then the median all medians was calculated per arm.
measure: Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Crowdsourced Raters
time frame: 6 months
description: The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.
measure: Hypertrophic Scarring (HTS) as Assessed by Score on the Manchester Scar Scale (MSS) Rated by Crowdsourced Raters
time frame: 12 months
description: The Manchester Scar Scale (MSS) assesses color match to surrounding skin, skin texture, contour, and distortion, and total MSS score ranges from 4 to 14, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.
measure: Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Crowdsourced Raters
time frame: 6 months
description: The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.
measure: Hypertrophic Scarring (HTS) as Assessed by Score on the Modified Scar Rating Scale (MSRS) Rated by Crowdsourced Raters
time frame: 12 months
description: The Modified Scar Rating Scale (MSRS) assesses surface appearance, scar height, and color mismatch, and total MSRS score ranges from 3 to 12, with a higher score indicating worse scarring. Scars were analyzed by crowdsourced raters via Amazon Mechanical Turk. The crowdsourced raters evaluated frontal and basal photographs of participants. 100 unique responses were elicited per participant. The mean of all crowdsourced ratings for each arm is reported per arm.
arm group label: Botulinum Toxin
arm group type: Experimental
description: Injection of botulinum toxin into cleft lip at time of surgical repair.
arm group label: Saline
arm group type: Placebo Comparator
description: Injection of normal saline into cleft lip at time of surgical repair.
intervention type: Drug
intervention name: Botulinum Toxin Type A
description: Injection of botulinum toxin at the time of surgery at cleft lip repair site. Botulinum toxin will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.
arm group label: Botulinum Toxin
intervention type: Drug
intervention name: Normal Saline Injection
description: Injection of normal saline into cleft lip at time of surgical repair. Saline will be injected intraoperatively at 4 standardized sites in the cleft lip during surgical repair.
arm group label: Saline
criteria: 
gender: All
minimum age: N/A
maximum age: 6 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Jaecel O Shah, MD
role: Principal Investigator
affiliation: UTHealth
facility: 
country: United States
citation: Pascual-Pascual SI, Pascual-Castroviejo I. Safety of botulinum toxin type A in children younger than 2 years. Eur J Paediatr Neurol. 2009 Nov;13(6):511-5. doi: 10.1016/j.ejpn.2008.10.006. Epub 2008 Nov 25.
PMID: 19036619
citation: Galarraga IM. Use of botulinum toxin in cheiloplasty: A new method to decrease tension. Can J Plast Surg. 2009 Fall;17(3):e1-2. doi: 10.1177/229255030901700313.
PMID: 20808741
citation: Alvarez CM, De Vera MA, Chhina H, Williams L, Durlacher K, Kaga S. The use of botulinum type A toxin in the treatment of idiopathic clubfoot: 5-year follow-up. J Pediatr Orthop. 2009 Sep;29(6):570-5. doi: 10.1097/BPO.0b013e3181b2b3d4.
PMID: 19700985
citation: Gassner HG, Sherris DA, Friedman O. Botulinum toxin-induced immobilization of lower facial wounds. Arch Facial Plast Surg. 2009 Mar-Apr;11(2):140-2. doi: 10.1001/archfacial.2009.3. No abstract available.
PMID: 19289689
citation: Christiansen G, Mohney BG, Baratz KH, Bradley EA. Botulinum toxin for the treatment of congenital entropion. Am J Ophthalmol. 2004 Jul;138(1):153-5. doi: 10.1016/j.ajo.2004.02.023.
PMID: 15234303
citation: Sherris DA, Gassner HG. Botulinum toxin to minimize facial scarring. Facial Plast Surg. 2002 Feb;18(1):35-9. doi: 10.1055/s-2002-19825.
PMID: 11823931
citation: Sykes JM. Management of the cleft lip deformity. Facial Plast Surg Clin North Am. 2001 Feb;9(1):37-50.
PMID: 11465005
citation: Seibert RW. Bilateral cleft nasal repair. Facial Plast Surg. 2000;16(1):69-78. doi: 10.1055/s-2000-7328.
PMID: 11802349
citation: Millard DR Jr. Embryonic rationale for the primary correction of classical congenital clefts of the lip and palate. Ann R Coll Surg Engl. 1994 May;76(3):150-60.
PMID: 8017808
citation: Witt PD, Hardesty RA. Rotation-advancement repair of the unilateral cleft lip. One center's perspective. Clin Plast Surg. 1993 Oct;20(4):633-45.
PMID: 8275629
citation: Lee JS, Lee KB, Lee YR, Choi YN, Park CW, Park SD, Jung DH, Lee CS. Botulinum Toxin Treatment on Upper Limb Function in School Age Children With Bilateral Spastic Cerebral Palsy: One Year Follow-up. Ann Rehabil Med. 2013 Jun;37(3):328-35. doi: 10.5535/arm.2013.37.3.328. Epub 2013 Jun 30.
PMID: 23869330
responsible party type: Principal Investigator
investigator affiliation: The University of Texas Health Science Center, Houston
investigator full name: Matthew Greives
investigator title: Associate Professor
mesh term: Cleft Palate
mesh term: Cleft Lip
mesh term: Botulinum Toxins
mesh term: Botulinum Toxins, Type A
mesh term: abobotulinumtoxinA
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Small sample size; inconsistency in acquiring post-op photos for some; 12 month analysis may be skewed by Botox's short duration of action; crowdsourced raters were not a generalized sample of the population
point of contact: 