<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/NCT01706952</url>
  </required_header>
  <id_info>
    <org_study_id>12-251-SDR</org_study_id>
    <nct_id>NCT01706952</nct_id>
  </id_info>
  <brief_title>Comparison of Topical Vasoconstriction in Endoscopic Sinus Surgery</brief_title>
  <official_title>Comparison of Topical Vasoconstriction in Endoscopic Sinus Surgery: Cocaine Versus Adrenaline</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Marc Tewfik</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McGill University Health Centre/Research Institute of the McGill University Health Centre</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of our study is to assess the effect of topical vasoconstriction (cocaine 4%&#xD;
      versus adrenaline 1/1000) on the surgical field during endoscopic sinus surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic Rhinosinusitis (CRS) is one of the most common chronic illnesses in North America,&#xD;
      with an incidence of approximately 13 per cent in the US.&#xD;
&#xD;
      Endoscopic sinus surgery (ESS) has become standard treatment for patients with chronic&#xD;
      rhinosinusitis (CRS) unresponsive to maximum medical treatment. The success of surgery&#xD;
      depends on several factors, an adequate surgical field is among the most important factors in&#xD;
      preventing complications in ESS.&#xD;
&#xD;
      Topical vasoconstrictors, such as adrenaline and cocaine has been widely used. To date no&#xD;
      studies exist comparing the use of topical cocaine with adrenaline in ESS.&#xD;
&#xD;
      The purpose of this study is to assess the effect of topical cocaine 4% versus adrenaline on&#xD;
      intra-operative bleeding during ESS and to describe the phisiologic changes with the use of&#xD;
      topical vasocontrictors. A secondary objective is to describe the phisiologic changes with&#xD;
      the use of topical vasocontrictors&#xD;
&#xD;
      Study Design:&#xD;
&#xD;
      A prospective randomized single-blind controlled trial will be conducted. The surgeon&#xD;
      performing the ESS and evaluating the bleeding will not be present at the time of injection,&#xD;
      and so will remain blinded.&#xD;
&#xD;
      All patients over the age of 18 years undergoing bilateral ESS for chronic sinusitis at&#xD;
      McGill University Health Center will be invited to participate. The study will be conducted&#xD;
      from November 2012 until the number required of patients is enrolled.&#xD;
&#xD;
      Topical vasoconstriction technique After oral intubation, vital signs and all anaesthetic&#xD;
      parameters will be kept as constant as possible for the duration of the surgery. Three cotton&#xD;
      neuropatties will be soaked with 4% cocaine. One neuropattie will be placed in the&#xD;
      sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle&#xD;
      turbinates on the side that the randomization has determined. In the other side, three cotton&#xD;
      neuropaties will be soaked with adrenaline 1:1000 and placed in the same positions than the&#xD;
      others. Then the patient will be draped and both sides will be injected with xylocaine 2% and&#xD;
      adrenaline 1:100.000. After this we will wait for 10 minutes and the surgery will be&#xD;
      initiated.&#xD;
&#xD;
      At the commencement of surgery and at regular 15-minute intervals, the operating surgeon will&#xD;
      estimate the intensity of bleeding in the operative field. The extent of nasal bleeding will&#xD;
      be evaluated according to the validated scale used by Boezaart. At each assessment, other&#xD;
      parameters including mean arterial blood pressure (MAP), heart rate, and end tidal CO2 will&#xD;
      be recorded into a chart by the co-investigator.&#xD;
&#xD;
      The total blood loss will be collected and recorded separately for each side. Separate&#xD;
      suction tubes and canisters will be used for each side. The total blood loss will be measured&#xD;
      by subtracting the amount of saline solution used to rinse the surgical field from the amount&#xD;
      of blood and fluids suctioned from the surgical field. Although this method of estimating the&#xD;
      intra operative blood loss is not flawless as some blood and fluids usually fall posteriorly&#xD;
      into the nasopharynx and are later suctioned by the anesthesiologist prior to extubation,&#xD;
      this amount is deemed to be negligible.&#xD;
&#xD;
      Proposed data analysis: The data will be collected by the co-investigator. Patient names and&#xD;
      other specific identifiers will not be included. Data will be entered into an Excel&#xD;
      spreadsheet and statistical analysis will be applied with SPSS vs.13.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 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>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To Estimate the Change in Bleeding Category (Surgical Field Improvement) as Measured on a Six-point Scale, Measured From 0 (Best Case) to 5 (Worst Case).</measure>
    <time_frame>Every 15 minutes until 300 minutes</time_frame>
    <description>0 No bleeding.&#xD;
Slight bleeding - no suctioning of blood required.&#xD;
Slight bleeding - occasional suctioning required. Surgical field not threatened.&#xD;
Slight bleeding - frequent suctioning required. Bleeding threatens surgical field a few seconds after suction is removed.&#xD;
Moderate bleeding - frequent suctioning required. Bleeding threatens surgical field directly after suction is removed.&#xD;
Severe bleeding - constant suctioning required. Bleeding appears faster than can be removed by suction. Surgical field severely threatened and surgery not possible.&#xD;
For the primary objective of surgical field grade, we calculated the mean within sides treated with cocaine vs adrenaline and assessed its difference</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Heart Rate</measure>
    <time_frame>Every 15 minutes until 300 minutes</time_frame>
    <description>The heart rate (heart beats for minutes) will be recorded every 15 minutes, until the surgery is over or until 300 minutes.&#xD;
The Co-investigator will record this data in a special data sheeet For the secondary objective of Heart rate, we calculated the average within sides treated with cocaine vs adrenaline and assessed its difference</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood Pressure</measure>
    <time_frame>Every 15 minutes or until 300 minutes</time_frame>
    <description>The mean blood pressure, defined as the average arterial pressure during a single cardiac cycle, will be recorded every 15 minutes, until the surgery is over or until 300 minutes.&#xD;
For the secondary objective of blood pressure, we calculated the mean within sides treated with cocaine vs adrenaline and assessed its difference</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>End Tidal CO2</measure>
    <time_frame>Every 15 minutes or until 300 minutes</time_frame>
    <description>The concentration of carbon dioxide (CO2) in the respiratory gases will be recorded every 15 minutes or until 300 minutes.&#xD;
For the secondary objective of concentration of carbon dioxide, we calculated the mean within sides treated with cocaine vs adrenaline and assessed its difference</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Chronic Sinusitis</condition>
  <arm_group>
    <arm_group_label>Cocaine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cocaine 4%. Three cotton neuropatties will be soaked with 4% cocaine. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This intervention will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Adrenaline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Adrenaline 1/1.000 Three cotton neuropatties will be soaked with Adrenaline 1/1,000. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cocaine</intervention_name>
    <description>Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).</description>
    <arm_group_label>Adrenaline</arm_group_label>
    <arm_group_label>Cocaine</arm_group_label>
    <other_name>Brand Name: Cocaine Hydrochloride Sterile Topical Solution</other_name>
    <other_name>Generic Name: Cocaine Hydrochloride Sterile Topical Solution</other_name>
    <other_name>Active Ingredients: Cocaine hydrochloride</other_name>
    <other_name>Concentration: 4%</other_name>
    <other_name>Code: 1200</other_name>
    <other_name>Format: 5 x 5 mL</other_name>
    <other_name>DIN: 01962388</other_name>
    <other_name>UPC: 057513012006</other_name>
    <other_name>Preservative: Yes</other_name>
    <other_name>Special feature: Latex Free Stopper</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adrenaline</intervention_name>
    <description>Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).</description>
    <arm_group_label>Adrenaline</arm_group_label>
    <arm_group_label>Cocaine</arm_group_label>
    <other_name>Epinephrine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Patients older than 18 years undergoing bilateral ESS for chronic sinusitis.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with heart disease&#xD;
&#xD;
          -  History of bleeding diathesis&#xD;
&#xD;
          -  Patients with untreated or poorly controlled high blood pressure&#xD;
&#xD;
          -  Aspirin, anticoagulant or natural herbal medication usage in the last 4 weeks&#xD;
&#xD;
          -  Hypersensitivity to adrenaline or cocaine&#xD;
&#xD;
          -  Significant asymmetry between the right and left side disease extent as determine by&#xD;
             findings on their pre-operative CT scan and nasal endoscopy.&#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>Marc A Tewfik, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Constanza J Valdes, MD</last_name>
    <role>Study Chair</role>
    <affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mark Samaha, MD</last_name>
    <role>Study Chair</role>
    <affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Otolaryngology-Head and Neck Surgery. McGill University Health Center</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3A 1A1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <results_reference>
    <citation>Valdes CJ, Bogado M, Rammal A, Samaha M, Tewfik MA. Topical cocaine vs adrenaline in endoscopic sinus surgery: a blinded randomized controlled study. Int Forum Allergy Rhinol. 2014 Aug;4(8):646-50. doi: 10.1002/alr.21325. Epub 2014 Mar 26.</citation>
    <PMID>24678064</PMID>
  </results_reference>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>October 3, 2012</study_first_submitted>
  <study_first_submitted_qc>October 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2012</study_first_posted>
  <results_first_submitted>August 10, 2014</results_first_submitted>
  <results_first_submitted_qc>March 22, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 3, 2017</results_first_posted>
  <last_update_submitted>March 22, 2017</last_update_submitted>
  <last_update_submitted_qc>March 22, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</investigator_affiliation>
    <investigator_full_name>Marc Tewfik</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Endoscopic sinus surgery</keyword>
  <keyword>Bleeding</keyword>
  <keyword>Topical Vasocontriction</keyword>
  <keyword>Cocaine</keyword>
  <keyword>Adrenaline</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sinusitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epinephrine</mesh_term>
    <mesh_term>Racepinephrine</mesh_term>
    <mesh_term>Cocaine</mesh_term>
    <mesh_term>Pharmaceutical Solutions</mesh_term>
    <mesh_term>Epinephryl borate</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cocaine/Adrenaline</title>
          <description>Cocaine: Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).&#xD;
Adrenaline: Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).&#xD;
Three cotton neuropatties will be placed in each side of the nostril. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This intervention will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>23 were male, 14 were female</population>
      <group_list>
        <group group_id="B1">
          <title>Cocaine/Adrenaline</title>
          <description>Three cotton neuropatties will be placed in each nostril. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This intervention will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.&#xD;
Cocaine: Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).&#xD;
Adrenaline: Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="37"/>
          </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="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="47.92" spread="16.51"/>
                  </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="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </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>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>To Estimate the Change in Bleeding Category (Surgical Field Improvement) as Measured on a Six-point Scale, Measured From 0 (Best Case) to 5 (Worst Case).</title>
        <description>0 No bleeding.&#xD;
Slight bleeding - no suctioning of blood required.&#xD;
Slight bleeding - occasional suctioning required. Surgical field not threatened.&#xD;
Slight bleeding - frequent suctioning required. Bleeding threatens surgical field a few seconds after suction is removed.&#xD;
Moderate bleeding - frequent suctioning required. Bleeding threatens surgical field directly after suction is removed.&#xD;
Severe bleeding - constant suctioning required. Bleeding appears faster than can be removed by suction. Surgical field severely threatened and surgery not possible.&#xD;
For the primary objective of surgical field grade, we calculated the mean within sides treated with cocaine vs adrenaline and assessed its difference</description>
        <time_frame>Every 15 minutes until 300 minutes</time_frame>
        <population>EACH SIDE WAS EVALUATED SEPARATELY</population>
        <group_list>
          <group group_id="O1">
            <title>Cocaine SIDE</title>
            <description>Cocaine 4%. Three cotton neuropatties will be soaked with 4% cocaine. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This intervention will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.&#xD;
Cocaine: Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).&#xD;
Adrenaline: Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).</description>
          </group>
          <group group_id="O2">
            <title>Adrenaline SIDE</title>
            <description>Adrenaline 1/1.000 Three cotton neuropatties will be soaked with Adrenaline 1/1,000. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.&#xD;
Cocaine: Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).&#xD;
Adrenaline: Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).</description>
          </group>
        </group_list>
        <measure>
          <title>To Estimate the Change in Bleeding Category (Surgical Field Improvement) as Measured on a Six-point Scale, Measured From 0 (Best Case) to 5 (Worst Case).</title>
          <description>0 No bleeding.&#xD;
Slight bleeding - no suctioning of blood required.&#xD;
Slight bleeding - occasional suctioning required. Surgical field not threatened.&#xD;
Slight bleeding - frequent suctioning required. Bleeding threatens surgical field a few seconds after suction is removed.&#xD;
Moderate bleeding - frequent suctioning required. Bleeding threatens surgical field directly after suction is removed.&#xD;
Severe bleeding - constant suctioning required. Bleeding appears faster than can be removed by suction. Surgical field severely threatened and surgery not possible.&#xD;
For the primary objective of surgical field grade, we calculated the mean within sides treated with cocaine vs adrenaline and assessed its difference</description>
          <population>EACH SIDE WAS EVALUATED SEPARATELY</population>
          <units>units 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="37"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.17" spread="0.70"/>
                    <measurement group_id="O2" value="2.04" spread="0.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Data analysis was performed using SPSS version 13 for Windows (SPSS Inc, Chicago, IL). A power study was per formed with a power of 80% and a clinically significant difference in bleeding between the sides of 20% with a significance level of 5% (p &lt; 0.05).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <non_inferiority_desc>For surgical field grade, we calculated the mean within sides and assessed its difference, reporting a 95% confidence interval as calculated by a Student t test. We used the average per patient over time.</non_inferiority_desc>
            <p_value>0.05</p_value>
            <method>t-test, 2 sided</method>
            <other_analysis_desc>For the primary objective of surgical field grade, we calculated the mean within sides treated with cocaine vs adrenaline and assessed its difference, reporting a 95% con- fidence interval as calculated by a Student t test. As all of these values were measured over time, we used the average per patient over time. The total blood loss per side within subjects was also calculated, with 95% confidence interval again calculated by a Student t test. Once again, we took the average per patient over time as the main outcome.&#xD;
Finally, we used a linear regression with surgical field improvement as the outcome and HR, MAP, or etCO2 as covariates, to investigate which variables may be related to the outcome. As these measures were taken over time, we used repeated measures analysis to investigate how these items correlate over time.&#xD;
In addition to the operating surgeon, the statistician was blinded to the vasoconstrictor allocation.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Heart Rate</title>
        <description>The heart rate (heart beats for minutes) will be recorded every 15 minutes, until the surgery is over or until 300 minutes.&#xD;
The Co-investigator will record this data in a special data sheeet For the secondary objective of Heart rate, we calculated the average within sides treated with cocaine vs adrenaline and assessed its difference</description>
        <time_frame>Every 15 minutes until 300 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cocaine SIDE</title>
            <description>Cocaine 4%. Three cotton neuropatties will be soaked with 4% cocaine. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This intervention will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.&#xD;
Cocaine: Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).&#xD;
Adrenaline: Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).</description>
          </group>
          <group group_id="O2">
            <title>Adrenaline SIDE</title>
            <description>Adrenaline 1/1.000 Three cotton neuropatties will be soaked with Adrenaline 1/1,000. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.&#xD;
Cocaine: Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).&#xD;
Adrenaline: Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).</description>
          </group>
        </group_list>
        <measure>
          <title>Heart Rate</title>
          <description>The heart rate (heart beats for minutes) will be recorded every 15 minutes, until the surgery is over or until 300 minutes.&#xD;
The Co-investigator will record this data in a special data sheeet For the secondary objective of Heart rate, we calculated the average within sides treated with cocaine vs adrenaline and assessed its difference</description>
          <units>Heart Beats per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.68" spread="13.64"/>
                    <measurement group_id="O2" value="73.62" spread="14.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Blood Pressure</title>
        <description>The mean blood pressure, defined as the average arterial pressure during a single cardiac cycle, will be recorded every 15 minutes, until the surgery is over or until 300 minutes.&#xD;
For the secondary objective of blood pressure, we calculated the mean within sides treated with cocaine vs adrenaline and assessed its difference</description>
        <time_frame>Every 15 minutes or until 300 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cocaine SIDE</title>
            <description>Cocaine 4%. Three cotton neuropatties will be soaked with 4% cocaine. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This intervention will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.&#xD;
Cocaine: Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).&#xD;
Adrenaline: Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).</description>
          </group>
          <group group_id="O2">
            <title>Adrenaline SIDE</title>
            <description>Adrenaline 1/1.000 Three cotton neuropatties will be soaked with Adrenaline 1/1,000. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.&#xD;
Cocaine: Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).&#xD;
Adrenaline: Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).</description>
          </group>
        </group_list>
        <measure>
          <title>Blood Pressure</title>
          <description>The mean blood pressure, defined as the average arterial pressure during a single cardiac cycle, will be recorded every 15 minutes, until the surgery is over or until 300 minutes.&#xD;
For the secondary objective of blood pressure, we calculated the mean within sides treated with cocaine vs adrenaline and assessed its difference</description>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.02" spread="11.94"/>
                    <measurement group_id="O2" value="68.41" spread="9.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>End Tidal CO2</title>
        <description>The concentration of carbon dioxide (CO2) in the respiratory gases will be recorded every 15 minutes or until 300 minutes.&#xD;
For the secondary objective of concentration of carbon dioxide, we calculated the mean within sides treated with cocaine vs adrenaline and assessed its difference</description>
        <time_frame>Every 15 minutes or until 300 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cocaine SIDE</title>
            <description>Cocaine 4%. Three cotton neuropatties will be soaked with 4% cocaine. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This intervention will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.&#xD;
Cocaine: Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).&#xD;
Adrenaline: Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).</description>
          </group>
          <group group_id="O2">
            <title>Adrenaline SIDE</title>
            <description>Adrenaline 1/1.000 Three cotton neuropatties will be soaked with Adrenaline 1/1,000. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.&#xD;
Cocaine: Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).&#xD;
Adrenaline: Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).</description>
          </group>
        </group_list>
        <measure>
          <title>End Tidal CO2</title>
          <description>The concentration of carbon dioxide (CO2) in the respiratory gases will be recorded every 15 minutes or until 300 minutes.&#xD;
For the secondary objective of concentration of carbon dioxide, we calculated the mean within sides treated with cocaine vs adrenaline and assessed its difference</description>
          <units>Percentage of carbon dioxide</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.26" spread="3.24"/>
                    <measurement group_id="O2" value="31.69" spread="2.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Participants were followed for the duration of hospital stay, an average of 8 hours, maximum stay up to 24 hours.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Cocaine</title>
          <description>Cocaine 4%. Three cotton neuropatties will be soaked with 4% cocaine. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This intervention will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.&#xD;
Cocaine: Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).&#xD;
Adrenaline: Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).</description>
        </group>
        <group group_id="E2">
          <title>Adrenaline</title>
          <description>Adrenaline 1/1.000 Three cotton neuropatties will be soaked with Adrenaline 1/1,000. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.&#xD;
This will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.&#xD;
Cocaine: Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).&#xD;
Adrenaline: Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </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="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Marc A. Tewfik</name_or_title>
      <organization>McGill University Health Centre</organization>
      <phone>+15147976673</phone>
      <email>marc.tewfik@mcgill.ca</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/NCT01706952
org study id: 12-251-SDR
nct id: NCT01706952
lead sponsor: 
has dmc: No
The purpose of our study is to assess the effect of topical vasoconstriction (cocaine 4%
      versus adrenaline 1/1000) on the surgical field during endoscopic sinus surgery.
Chronic Rhinosinusitis (CRS) is one of the most common chronic illnesses in North America,
      with an incidence of approximately 13 per cent in the US.

      Endoscopic sinus surgery (ESS) has become standard treatment for patients with chronic
      rhinosinusitis (CRS) unresponsive to maximum medical treatment. The success of surgery
      depends on several factors, an adequate surgical field is among the most important factors in
      preventing complications in ESS.

      Topical vasoconstrictors, such as adrenaline and cocaine has been widely used. To date no
      studies exist comparing the use of topical cocaine with adrenaline in ESS.

      The purpose of this study is to assess the effect of topical cocaine 4% versus adrenaline on
      intra-operative bleeding during ESS and to describe the phisiologic changes with the use of
      topical vasocontrictors. A secondary objective is to describe the phisiologic changes with
      the use of topical vasocontrictors

      Study Design:

      A prospective randomized single-blind controlled trial will be conducted. The surgeon
      performing the ESS and evaluating the bleeding will not be present at the time of injection,
      and so will remain blinded.

      All patients over the age of 18 years undergoing bilateral ESS for chronic sinusitis at
      McGill University Health Center will be invited to participate. The study will be conducted
      from November 2012 until the number required of patients is enrolled.

      Topical vasoconstriction technique After oral intubation, vital signs and all anaesthetic
      parameters will be kept as constant as possible for the duration of the surgery. Three cotton
      neuropatties will be soaked with 4% cocaine. One neuropattie will be placed in the
      sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle
      turbinates on the side that the randomization has determined. In the other side, three cotton
      neuropaties will be soaked with adrenaline 1:1000 and placed in the same positions than the
      others. Then the patient will be draped and both sides will be injected with xylocaine 2% and
      adrenaline 1:100.000. After this we will wait for 10 minutes and the surgery will be
      initiated.

      At the commencement of surgery and at regular 15-minute intervals, the operating surgeon will
      estimate the intensity of bleeding in the operative field. The extent of nasal bleeding will
      be evaluated according to the validated scale used by Boezaart. At each assessment, other
      parameters including mean arterial blood pressure (MAP), heart rate, and end tidal CO2 will
      be recorded into a chart by the co-investigator.

      The total blood loss will be collected and recorded separately for each side. Separate
      suction tubes and canisters will be used for each side. The total blood loss will be measured
      by subtracting the amount of saline solution used to rinse the surgical field from the amount
      of blood and fluids suctioned from the surgical field. Although this method of estimating the
      intra operative blood loss is not flawless as some blood and fluids usually fall posteriorly
      into the nasopharynx and are later suctioned by the anesthesiologist prior to extubation,
      this amount is deemed to be negligible.

      Proposed data analysis: The data will be collected by the co-investigator. Patient names and
      other specific identifiers will not be included. Data will be entered into an Excel
      spreadsheet and statistical analysis will be applied with SPSS vs.13.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Single (Care Provider)
measure: To Estimate the Change in Bleeding Category (Surgical Field Improvement) as Measured on a Six-point Scale, Measured From 0 (Best Case) to 5 (Worst Case).
time frame: Every 15 minutes until 300 minutes
description: 0 No bleeding.
Slight bleeding - no suctioning of blood required.
Slight bleeding - occasional suctioning required. Surgical field not threatened.
Slight bleeding - frequent suctioning required. Bleeding threatens surgical field a few seconds after suction is removed.
Moderate bleeding - frequent suctioning required. Bleeding threatens surgical field directly after suction is removed.
Severe bleeding - constant suctioning required. Bleeding appears faster than can be removed by suction. Surgical field severely threatened and surgery not possible.
For the primary objective of surgical field grade, we calculated the mean within sides treated with cocaine vs adrenaline and assessed its difference
measure: Heart Rate
time frame: Every 15 minutes until 300 minutes
description: The heart rate (heart beats for minutes) will be recorded every 15 minutes, until the surgery is over or until 300 minutes.
The Co-investigator will record this data in a special data sheeet For the secondary objective of Heart rate, we calculated the average within sides treated with cocaine vs adrenaline and assessed its difference
measure: Blood Pressure
time frame: Every 15 minutes or until 300 minutes
description: The mean blood pressure, defined as the average arterial pressure during a single cardiac cycle, will be recorded every 15 minutes, until the surgery is over or until 300 minutes.
For the secondary objective of blood pressure, we calculated the mean within sides treated with cocaine vs adrenaline and assessed its difference
measure: End Tidal CO2
time frame: Every 15 minutes or until 300 minutes
description: The concentration of carbon dioxide (CO2) in the respiratory gases will be recorded every 15 minutes or until 300 minutes.
For the secondary objective of concentration of carbon dioxide, we calculated the mean within sides treated with cocaine vs adrenaline and assessed its difference
arm group label: Cocaine
arm group type: Experimental
description: Cocaine 4%. Three cotton neuropatties will be soaked with 4% cocaine. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.
This intervention will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.
arm group label: Adrenaline
arm group type: Active Comparator
description: Adrenaline 1/1.000 Three cotton neuropatties will be soaked with Adrenaline 1/1,000. One neuropattie will be placed in the sphenoethmoidal recess, one in the middle meatus, and one in the anterior end of the middle turbinates on the side that the randomization has determined.
This will be done before the beginning of the surgery, and will be left in the nose for 10 minutes, this will be done just once. After the 10 minutes, the neuropatties will be taken out of the nose.
intervention type: Drug
intervention name: Cocaine
description: Pledgets soaked in 4% cocaine hydrochloride solution were placed intranasally (one side).
arm group label: Adrenaline
arm group label: Cocaine
other name: Brand Name: Cocaine Hydrochloride Sterile Topical Solution
other name: Generic Name: Cocaine Hydrochloride Sterile Topical Solution
other name: Active Ingredients: Cocaine hydrochloride
other name: Concentration: 4%
other name: Code: 1200
other name: Format: 5 x 5 mL
other name: DIN: 01962388
other name: UPC: 057513012006
other name: Preservative: Yes
other name: Special feature: Latex Free Stopper
intervention type: Drug
intervention name: Adrenaline
description: Pledgets soaked in 1/1000 adrenaline solution were placed intranasally (one side).
arm group label: Adrenaline
arm group label: Cocaine
other name: Epinephrine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marc A Tewfik, MD
role: Principal Investigator
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
last name: Constanza J Valdes, MD
role: Study Chair
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
last name: Mark Samaha, MD
role: Study Chair
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
facility: 
country: Canada
citation: Valdes CJ, Bogado M, Rammal A, Samaha M, Tewfik MA. Topical cocaine vs adrenaline in endoscopic sinus surgery: a blinded randomized controlled study. Int Forum Allergy Rhinol. 2014 Aug;4(8):646-50. doi: 10.1002/alr.21325. Epub 2014 Mar 26.
PMID: 24678064
responsible party type: Sponsor-Investigator
investigator affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
investigator full name: Marc Tewfik
investigator title: Principal Investigator
mesh term: Sinusitis
mesh term: Epinephrine
mesh term: Racepinephrine
mesh term: Cocaine
mesh term: Pharmaceutical Solutions
mesh term: Epinephryl borate
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 