<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/NCT01693185</url>
  </required_header>
  <id_info>
    <org_study_id>KUH1160048</org_study_id>
    <nct_id>NCT01693185</nct_id>
  </id_info>
  <brief_title>Remifentanil Only vs. Midazolam and Meperidine During Elective Colonoscopy</brief_title>
  <acronym>remifentanil</acronym>
  <official_title>Remifentanil Only vs. Combination Group Midazolam + Meperidine During Elective Colonoscopy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Konkuk University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Konkuk University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the present study is to compare patient's recovery times after elective&#xD;
      colonoscopy employing remifentanil only vs conventional combination of midazolam and&#xD;
      meperidine&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A regimen with combined administration of midazolam and meperidine has been widely used and&#xD;
      provides quite satisfactory sedation as well as analgesia during colonoscopy. However, the&#xD;
      relatively long duration of midazolam and meperidine often prolongs the recovery time after&#xD;
      colonoscopy and delays discharge time. (Reimann FM , Samson U , Derad I et al. Synergistic&#xD;
      sedation with low-dose midazolam and propofol for colonoscopies . Endoscopy 2000 ; 32 : 239 -&#xD;
      44).&#xD;
&#xD;
      Remifentanil, an ultra-short-acting opioid, provides excellent pain control during&#xD;
      colonoscopy and its rapid onset and offset times are advantages over other conventional&#xD;
      opioids including meperidine, in avoiding prolonged discharge time after the colonoscopy.&#xD;
&#xD;
      A total 54 patients, aged 18-65 years in American Society of Anesthesiologists physical&#xD;
      status (ASA PS)1 and 2, scheduled for elective colonoscopy under Monitored Anesthesia Care in&#xD;
      a University Hospital, will be recruited after obtaining written informed consent during the&#xD;
      patients' first visit to outpatient/inpatient clinic for interview.&#xD;
&#xD;
      Predetermined patient identification numbers (PIN) and enrolment order were placed in sealed&#xD;
      envelopes, and all patients were randomly assigned, at recruitment, to the&#xD;
      midazolam-meperidine combination (group-MM) or remifentanil alone (group-R). If a patient was&#xD;
      excluded during the study, the following patient assumed the status of the excluded patient.&#xD;
&#xD;
      Patients are allocated into one of two groups, Group 1 and Group 2 (27 patients each)&#xD;
      according to the PIN at the recruitment.&#xD;
&#xD;
      The exclusion criteria were as follows: refusal or inability to provide written informed&#xD;
      consent, age &lt;19 years, pregnancy, previous history of large bowel surgery, a psychiatric&#xD;
      disorder, an addictions to opiates or sedatives, a previous history of adverse events to any&#xD;
      drug used in the present study, and performance of any additional diagnostic procedure after&#xD;
      completion of colonoscopy.&#xD;
&#xD;
      All colonoscopic procedure is going to be performed by one Gastroenterologist (endoscopist).&#xD;
&#xD;
      On arriving in the endoscopy room, supplemental oxygen (2 L/min) was given through the mouth&#xD;
      and both nostrils via a specially designed nasal prong which could monitor the end-tidal CO2&#xD;
      (ETCO2) level.&#xD;
&#xD;
      Before drug administration, the basal values of mean blood pressure (MBP), heart rate (HR),&#xD;
      peripheral O2 saturation (SpO2), respiratory rate (RR), end-expiratory CO2 level (ETCO2), and&#xD;
      the bispectral index (BIS), were recorded by a single observer, who also monitored these&#xD;
      values every 5 min during entire colonoscopy procedures.&#xD;
&#xD;
      Supplemental oxygen (3 L/min) is given through nasal prong with capnography transducer in all&#xD;
      patients.&#xD;
&#xD;
      Two min before the colonoscopy procedure, a bolus midazolam of 0.03 mg/kg with a bolus&#xD;
      meperidine of 1.0 mg/kg are given intravenously over 60 sec in Group 1 or those of comparable&#xD;
      amount of diluted remifentanil 0.4 mcg/kg are given in Group 2 at the colonoscopy room, and a&#xD;
      continuous infusion of diluted remifentanil of 0.04 mcg/kg/min is followed in Group 2 or that&#xD;
      of comparable amount of normal saline (placebo) is followed in Group 1.&#xD;
&#xD;
      The patients are asked to rate the degree of pain and distress (reverse satisfaction) by a&#xD;
      100 mm Visual analogue scale (VAS; 0 = minimum, 100 = maximum) just after passing the scope,&#xD;
      during the scope, just after the completion of the colonoscopy and at the discharge from the&#xD;
      recovery unit.&#xD;
&#xD;
      After colonoscopy, the patients are transferred to the recovery unit and evaluated every 5&#xD;
      min until ready for discharge from the 30 min stay in the recovery unit.&#xD;
&#xD;
      The patients are considered recovered if when they achieved an Aldrete score of 10 (Aldrete&#xD;
      JA , Kroulik D . A postanesthetic recovery score. Anesth Analg 1970; 49: 924 - 34), have&#xD;
      stable vital signs, are able to tolerate oral fluids, have no nausea, vomiting, or itching,&#xD;
      and can walk unaided.&#xD;
&#xD;
      Assessment of readiness to ambulate is made by a blinded observer who remained with the&#xD;
      patient for the duration of recovery unit stay.&#xD;
&#xD;
      The observer is instructed that the patients are required to walk as if they were leaving the&#xD;
      recovery unit unescorted.&#xD;
&#xD;
      Aldrete score, patient pain and satisfaction (distress score) were determined every 5 min&#xD;
      during colonoscopy and after colonoscopy up to 30 min. Time for achieving Aldrete score 10,&#xD;
      patient's degree of pain, patient's satisfaction during and after colonoscopy, patient's&#xD;
      ability to recall the explanations and instructions given during and before colonoscopy are&#xD;
      determined and compared.&#xD;
&#xD;
      Aldrete score Respiration: Able to take deep breath and cough = 2, Dyspnea/shallow breathing&#xD;
      = 1, Apnea = 0 O2 saturation: Maintains &gt; 92% on room air =2, Needs O2 inhalation to maintain&#xD;
      O2 saturation &gt; 90% =1 , O2 saturation &lt; 90% even with supplemental oxygen =0 Consciousness:&#xD;
      Fully awake= 2, Arousable on calling = 1, Not responding = 0 Circulation: BP +/- 20 mm Hg&#xD;
      preop =2, BP +/- 20-50 mm Hg preop =1, BP +/- 50 mm Hg preop =0 Activity: Able to move 4&#xD;
      extremities = 2, Able to move 2 extremities = 1, Able to move 0 extremities = 0&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">August 2013</completion_date>
  <primary_completion_date type="Actual">February 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>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Recovery Time</measure>
    <time_frame>every 5 minutes after completing colonoscopy up to 30 min</time_frame>
    <description>Time from completing the colonoscopy to achieving Aldrete score 10 in the recovery unit&#xD;
Aldrete score&#xD;
Respiration: Able to take deep breath and cough = 2, Dyspnea/shallow breathing = 1, Apnea = 0&#xD;
O2 saturation: Maintains &gt; 92% on room air =2, Needs O2 inhalation to maintain O2 saturation &gt; 90% =1 , O2 saturation &lt; 90% even with supplemental oxygen =0&#xD;
Consciousness: Fully awake= 2, Arousable on calling = 1, Not responding = 0&#xD;
Circulation: BP +/- 20 mm Hg preop =2, BP +/- 20-50 mm Hg preop =1, BP +/- 50 mm Hg preop =0&#xD;
Activity: Able to move 4 extremities = 2, Able to move 2 extremities = 1, Able to move 0 extremities = 0&#xD;
To estimate the required sample size, we conducted a pilot study to measure the recovery of 10 patients in each of groups-MM and -R before the present study. The means and standard deviations were 22.5 ± 9.5 and 7.5 ± 9.2 min respectively. We wished to be able to distinguish a difference of 7.5 min, thus half of the observed difference.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Participants Assumed to Feel Frequent Pain</measure>
    <time_frame>during and after colonoscopy</time_frame>
    <description>patients sound &quot;Ah&quot; at feeling pain during colonosocpy: if a patients sounds &quot;Ah&quot; &gt; 6 times, the patient was assumed to feel frequent pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bispectra Lindex Score</measure>
    <time_frame>every 5 min during and after colonoscopy</time_frame>
    <description>Bispectral index (BIS) score 0-100 maximal sedation=0, maximal sedation=100</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient's Distress Score</measure>
    <time_frame>5 min after the end of colonoscopy</time_frame>
    <description>patients' distress in visual analogue scale 100 mm minimal distress=0, maximal distress=100</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endoscopist Satisfaction</measure>
    <time_frame>5 min after the colonoscopy</time_frame>
    <description>endoscopist's satisfaction after colonoscopy in visual analogue scale 100 mm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Indigence of Patient's Recall</measure>
    <time_frame>after colonoscopy</time_frame>
    <description>The numbers of patients who recalled instructions and explanations given during colonoscopy</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Diagnostic Colonoscopy Screening</condition>
  <arm_group>
    <arm_group_label>Remifentanil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>remifentanil of 0.04 mcg/kg/min with placebo (for midazolam) and placebo (for meperidine)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>midazolam and meperidine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>a bolus midazolam of 0.03 mg/kg a bolus meperidine of 1.0 mg/kg placebo (for remifentanil)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Remifentanil</intervention_name>
    <description>continuous infusion 0.4 mcg/kg/min</description>
    <arm_group_label>Remifentanil</arm_group_label>
    <other_name>Ultiva</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <description>bolus injection</description>
    <arm_group_label>midazolam and meperidine</arm_group_label>
    <other_name>dormicum</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Meperidine</intervention_name>
    <description>bolus injection for 30 sec 1.0 mg/kg</description>
    <arm_group_label>midazolam and meperidine</arm_group_label>
    <other_name>Pethidine Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo (for remifentanil)</intervention_name>
    <description>normal saline mimic diluted remifentanil</description>
    <arm_group_label>midazolam and meperidine</arm_group_label>
    <other_name>normal saline</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo (for midazolam)</intervention_name>
    <description>normal saline mimic to midazolam injection</description>
    <arm_group_label>Remifentanil</arm_group_label>
    <other_name>normal saline</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo (for meperidine)</intervention_name>
    <description>normal saline mimic meperidine injection</description>
    <arm_group_label>Remifentanil</arm_group_label>
    <other_name>normal saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged 19-65 years&#xD;
&#xD;
          -  American Society of Anesthesiologists physical status (ASA PS) 1-2&#xD;
&#xD;
          -  Patients scheduled for elective colonoscopy under Monitored Anesthesia Care in a&#xD;
             University Hospital&#xD;
&#xD;
          -  Patients who signed on written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The exclusion criteria are refusal or inability to provide written informed consent&#xD;
&#xD;
          -  Age &lt; 18 years&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Previous large bowel surgery&#xD;
&#xD;
          -  Psychiatric disorders&#xD;
&#xD;
          -  History of addiction to opiates and / or sedatives, and previous adverse reaction to&#xD;
             any drug used in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tae-Yop Kim, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Konkuk University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Konkuk University Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>143-729</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>May 2014</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2012</study_first_posted>
  <results_first_submitted>February 2, 2014</results_first_submitted>
  <results_first_submitted_qc>May 16, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">June 18, 2014</results_first_posted>
  <last_update_submitted>May 16, 2014</last_update_submitted>
  <last_update_submitted_qc>May 16, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 18, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Konkuk University Medical Center</investigator_affiliation>
    <investigator_full_name>Tae-Yop Kim, MD PhD</investigator_full_name>
    <investigator_title>Professor of Anesthesiology</investigator_title>
  </responsible_party>
  <keyword>colonoscopy</keyword>
  <keyword>remifentanil</keyword>
  <keyword>midazolam</keyword>
  <keyword>meperidine</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Meperidine</mesh_term>
    <mesh_term>Remifentanil</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Predetermined patient identification numbers and enrolment order were placed in sealed envelopes, and all patients were randomly assigned, at recruitment, to the midazolam-meperidine combination (group-MM) or remifentanil alone (group-R). If a patient was excluded during the study, the following patient assumed the status of the excluded patient.</recruitment_details>
      <pre_assignment_details>The exclusion criteria were applied. If a patient was excluded after recruitment and enrollment into the study, the following new patient assumed the status of the excluded patient.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Remifentanil</title>
          <description>remifentanil of 0.04 mcg/kg/min with placebo (for midazolam) and placebo (for meperidine)&#xD;
Remifentanil: continuous infusion 0.4 mcg/kg/min&#xD;
placebo (for midazolam): normal saline mimic to midazolam injection&#xD;
placebo (for meperidine): normal saline mimic meperidine injection</description>
        </group>
        <group group_id="P2">
          <title>Midazolam and Meperidine</title>
          <description>a bolus midazolam of 0.03 mg/kg a bolus meperidine of 1.0 mg/kg placebo (for remifentanil)&#xD;
Midazolam: bolus injection&#xD;
Meperidine: bolus injection for 30 sec 1.0 mg/kg&#xD;
placebo (for remifentanil): normal saline mimic diluted remifentanil</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>diagnostic procedure after colonoscopy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Patients with ASA PS class 1 or 2 undergoing elective colonoscopy under monitored anesthesia care</population>
      <group_list>
        <group group_id="B1">
          <title>Remifentanil</title>
          <description>remifentanil of 0.04 mcg/kg/min with placebo (for midazolam) and placebo (for meperidine)&#xD;
Remifentanil: continuous infusion 0.4 mcg/kg/min&#xD;
placebo (for midazolam): normal saline mimic to midazolam injection&#xD;
placebo (for meperidine): normal saline mimic meperidine injection</description>
        </group>
        <group group_id="B2">
          <title>Midazolam and Meperidine</title>
          <description>a bolus midazolam of 0.03 mg/kg a bolus meperidine of 1.0 mg/kg placebo (for remifentanil)&#xD;
Midazolam: bolus injection&#xD;
Meperidine: bolus injection for 30 sec 1.0 mg/kg&#xD;
placebo (for remifentanil): normal saline mimic diluted remifentanil</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="27"/>
            <count group_id="B2" value="27"/>
            <count group_id="B3" value="54"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.6" spread="12.7"/>
                    <measurement group_id="B2" value="53.0" spread="10.7"/>
                    <measurement group_id="B3" value="54.8" spread="11.8"/>
                  </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="16"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Recovery Time</title>
        <description>Time from completing the colonoscopy to achieving Aldrete score 10 in the recovery unit&#xD;
Aldrete score&#xD;
Respiration: Able to take deep breath and cough = 2, Dyspnea/shallow breathing = 1, Apnea = 0&#xD;
O2 saturation: Maintains &gt; 92% on room air =2, Needs O2 inhalation to maintain O2 saturation &gt; 90% =1 , O2 saturation &lt; 90% even with supplemental oxygen =0&#xD;
Consciousness: Fully awake= 2, Arousable on calling = 1, Not responding = 0&#xD;
Circulation: BP +/- 20 mm Hg preop =2, BP +/- 20-50 mm Hg preop =1, BP +/- 50 mm Hg preop =0&#xD;
Activity: Able to move 4 extremities = 2, Able to move 2 extremities = 1, Able to move 0 extremities = 0&#xD;
To estimate the required sample size, we conducted a pilot study to measure the recovery of 10 patients in each of groups-MM and -R before the present study. The means and standard deviations were 22.5 ± 9.5 and 7.5 ± 9.2 min respectively. We wished to be able to distinguish a difference of 7.5 min, thus half of the observed difference.</description>
        <time_frame>every 5 minutes after completing colonoscopy up to 30 min</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Remifentanil</title>
            <description>remifentanil of 0.04 mcg/kg/min with placebo (for midazolam) and placebo (for meperidine)&#xD;
Remifentanil: continuous infusion 0.4 mcg/kg/min&#xD;
placebo (for midazolam): normal saline mimic to midazolam injection&#xD;
placebo (for meperidine): normal saline mimic meperidine injection</description>
          </group>
          <group group_id="O2">
            <title>Midazolam and Meperidine</title>
            <description>a bolus midazolam of 0.03 mg/kg a bolus meperidine of 1.0 mg/kg placebo (for remifentanil)&#xD;
Midazolam: bolus injection&#xD;
Meperidine: bolus injection for 30 sec 1.0 mg/kg&#xD;
placebo (for remifentanil): normal saline mimic diluted remifentanil</description>
          </group>
        </group_list>
        <measure>
          <title>The Recovery Time</title>
          <description>Time from completing the colonoscopy to achieving Aldrete score 10 in the recovery unit&#xD;
Aldrete score&#xD;
Respiration: Able to take deep breath and cough = 2, Dyspnea/shallow breathing = 1, Apnea = 0&#xD;
O2 saturation: Maintains &gt; 92% on room air =2, Needs O2 inhalation to maintain O2 saturation &gt; 90% =1 , O2 saturation &lt; 90% even with supplemental oxygen =0&#xD;
Consciousness: Fully awake= 2, Arousable on calling = 1, Not responding = 0&#xD;
Circulation: BP +/- 20 mm Hg preop =2, BP +/- 20-50 mm Hg preop =1, BP +/- 50 mm Hg preop =0&#xD;
Activity: Able to move 4 extremities = 2, Able to move 2 extremities = 1, Able to move 0 extremities = 0&#xD;
To estimate the required sample size, we conducted a pilot study to measure the recovery of 10 patients in each of groups-MM and -R before the present study. The means and standard deviations were 22.5 ± 9.5 and 7.5 ± 9.2 min respectively. We wished to be able to distinguish a difference of 7.5 min, thus half of the observed difference.</description>
          <units>minute</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="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="10"/>
                    <measurement group_id="O2" value="30" lower_limit="15" upper_limit="30"/>
                  </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>Recovery time in patients administered remifentanil alone will be significantly shorter than that in patients administered midazolam-meperidine combination for colonoscopy.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.001</p_value>
            <p_value_desc>We wished to be able to distinguish a difference of 7.5 min,</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants Assumed to Feel Frequent Pain</title>
        <description>patients sound &quot;Ah&quot; at feeling pain during colonosocpy: if a patients sounds &quot;Ah&quot; &gt; 6 times, the patient was assumed to feel frequent pain.</description>
        <time_frame>during and after colonoscopy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Remifentanil</title>
            <description>remifentanil of 0.04 mcg/kg/min with placebo (for midazolam) and placebo (for meperidine)&#xD;
Remifentanil: continuous infusion 0.4 mcg/kg/min&#xD;
placebo (for midazolam): normal saline mimic to midazolam injection&#xD;
placebo (for meperidine): normal saline mimic meperidine injection</description>
          </group>
          <group group_id="O2">
            <title>Midazolam and Meperidine</title>
            <description>a bolus midazolam of 0.03 mg/kg a bolus meperidine of 1.0 mg/kg placebo (for remifentanil)&#xD;
Midazolam: bolus injection&#xD;
Meperidine: bolus injection for 30 sec 1.0 mg/kg&#xD;
placebo (for remifentanil): normal saline mimic diluted remifentanil</description>
          </group>
        </group_list>
        <measure>
          <title>Participants Assumed to Feel Frequent Pain</title>
          <description>patients sound &quot;Ah&quot; at feeling pain during colonosocpy: if a patients sounds &quot;Ah&quot; &gt; 6 times, the patient was assumed to feel frequent pain.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Bispectra Lindex Score</title>
        <description>Bispectral index (BIS) score 0-100 maximal sedation=0, maximal sedation=100</description>
        <time_frame>every 5 min during and after colonoscopy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Remifentanil</title>
            <description>remifentanil of 0.04 mcg/kg/min with placebo (for midazolam) and placebo (for meperidine)&#xD;
Remifentanil: continuous infusion 0.4 mcg/kg/min&#xD;
placebo (for midazolam): normal saline mimic to midazolam injection&#xD;
placebo (for meperidine): normal saline mimic meperidine injection</description>
          </group>
          <group group_id="O2">
            <title>Midazolam and Meperidine</title>
            <description>a bolus midazolam of 0.03 mg/kg a bolus meperidine of 1.0 mg/kg placebo (for remifentanil)&#xD;
Midazolam: bolus injection&#xD;
Meperidine: bolus injection for 30 sec 1.0 mg/kg&#xD;
placebo (for remifentanil): normal saline mimic diluted remifentanil</description>
          </group>
        </group_list>
        <measure>
          <title>Bispectra Lindex Score</title>
          <description>Bispectral index (BIS) score 0-100 maximal sedation=0, maximal sedation=100</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92" lower_limit="85" upper_limit="96"/>
                    <measurement group_id="O2" value="84" lower_limit="80" upper_limit="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient's Distress Score</title>
        <description>patients' distress in visual analogue scale 100 mm minimal distress=0, maximal distress=100</description>
        <time_frame>5 min after the end of colonoscopy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Remifentanil</title>
            <description>remifentanil of 0.04 mcg/kg/min with placebo (for midazolam) and placebo (for meperidine)&#xD;
Remifentanil: continuous infusion 0.4 mcg/kg/min&#xD;
placebo (for midazolam): normal saline mimic to midazolam injection&#xD;
placebo (for meperidine): normal saline mimic meperidine injection</description>
          </group>
          <group group_id="O2">
            <title>Midazolam and Meperidine</title>
            <description>a bolus midazolam of 0.03 mg/kg a bolus meperidine of 1.0 mg/kg placebo (for remifentanil)&#xD;
Midazolam: bolus injection&#xD;
Meperidine: bolus injection for 30 sec 1.0 mg/kg&#xD;
placebo (for remifentanil): normal saline mimic diluted remifentanil</description>
          </group>
        </group_list>
        <measure>
          <title>Patient's Distress Score</title>
          <description>patients' distress in visual analogue scale 100 mm minimal distress=0, maximal distress=100</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37" lower_limit="30" upper_limit="43"/>
                    <measurement group_id="O2" value="30" lower_limit="30" upper_limit="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Endoscopist Satisfaction</title>
        <description>endoscopist's satisfaction after colonoscopy in visual analogue scale 100 mm</description>
        <time_frame>5 min after the colonoscopy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Remifentanil</title>
            <description>remifentanil of 0.04 mcg/kg/min with placebo (for midazolam) and placebo (for meperidine)&#xD;
Remifentanil: continuous infusion 0.4 mcg/kg/min&#xD;
placebo (for midazolam): normal saline mimic to midazolam injection&#xD;
placebo (for meperidine): normal saline mimic meperidine injection</description>
          </group>
          <group group_id="O2">
            <title>Midazolam and Meperidine</title>
            <description>a bolus midazolam of 0.03 mg/kg a bolus meperidine of 1.0 mg/kg placebo (for remifentanil)&#xD;
Midazolam: bolus injection&#xD;
Meperidine: bolus injection for 30 sec 1.0 mg/kg&#xD;
placebo (for remifentanil): normal saline mimic diluted remifentanil</description>
          </group>
        </group_list>
        <measure>
          <title>Endoscopist Satisfaction</title>
          <description>endoscopist's satisfaction after colonoscopy in visual analogue scale 100 mm</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="5" upper_limit="10"/>
                    <measurement group_id="O2" value="20" lower_limit="10" upper_limit="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Indigence of Patient's Recall</title>
        <description>The numbers of patients who recalled instructions and explanations given during colonoscopy</description>
        <time_frame>after colonoscopy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Remifentanil</title>
            <description>remifentanil of 0.04 mcg/kg/min with placebo (for midazolam) and placebo (for meperidine)&#xD;
Remifentanil: continuous infusion 0.4 mcg/kg/min&#xD;
placebo (for midazolam): normal saline mimic to midazolam injection&#xD;
placebo (for meperidine): normal saline mimic meperidine injection</description>
          </group>
          <group group_id="O2">
            <title>Midazolam and Meperidine</title>
            <description>a bolus midazolam of 0.03 mg/kg a bolus meperidine of 1.0 mg/kg placebo (for remifentanil)&#xD;
Midazolam: bolus injection&#xD;
Meperidine: bolus injection for 30 sec 1.0 mg/kg&#xD;
placebo (for remifentanil): normal saline mimic diluted remifentanil</description>
          </group>
        </group_list>
        <measure>
          <title>Indigence of Patient's Recall</title>
          <description>The numbers of patients who recalled instructions and explanations given during colonoscopy</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>during and after colonosocpy, up to 30 min</time_frame>
      <desc>incidence (number of patients) of pulse oximetry &lt; 90% during colonoscopy during and after colonoscopy</desc>
      <group_list>
        <group group_id="E1">
          <title>Remifentanil</title>
          <description>remifentanil of 0.04 mcg/kg/min with placebo (for midazolam) and placebo (for meperidine)&#xD;
Remifentanil: continuous infusion 0.4 mcg/kg/min&#xD;
placebo (for midazolam): normal saline mimic to midazolam injection&#xD;
placebo (for meperidine): normal saline mimic meperidine injection</description>
        </group>
        <group group_id="E2">
          <title>Midazolam and Meperidine</title>
          <description>a bolus midazolam of 0.03 mg/kg a bolus meperidine of 1.0 mg/kg placebo (for remifentanil)&#xD;
Midazolam: bolus injection&#xD;
Meperidine: bolus injection for 30 sec 1.0 mg/kg&#xD;
placebo (for remifentanil): normal saline mimic diluted remifentanil</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="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Tae-Yop Kim, Professor of Anesthesiology</name_or_title>
      <organization>Konkuk University Medical Center</organization>
      <phone>82-2-2030-5445</phone>
      <email>taeyop@gmail.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01693185
org study id: KUH1160048
nct id: NCT01693185
lead sponsor: 
collaborator: 
has dmc: No
The aim of the present study is to compare patient's recovery times after elective
      colonoscopy employing remifentanil only vs conventional combination of midazolam and
      meperidine
A regimen with combined administration of midazolam and meperidine has been widely used and
      provides quite satisfactory sedation as well as analgesia during colonoscopy. However, the
      relatively long duration of midazolam and meperidine often prolongs the recovery time after
      colonoscopy and delays discharge time. (Reimann FM , Samson U , Derad I et al. Synergistic
      sedation with low-dose midazolam and propofol for colonoscopies . Endoscopy 2000 ; 32 : 239 -
      44).

      Remifentanil, an ultra-short-acting opioid, provides excellent pain control during
      colonoscopy and its rapid onset and offset times are advantages over other conventional
      opioids including meperidine, in avoiding prolonged discharge time after the colonoscopy.

      A total 54 patients, aged 18-65 years in American Society of Anesthesiologists physical
      status (ASA PS)1 and 2, scheduled for elective colonoscopy under Monitored Anesthesia Care in
      a University Hospital, will be recruited after obtaining written informed consent during the
      patients' first visit to outpatient/inpatient clinic for interview.

      Predetermined patient identification numbers (PIN) and enrolment order were placed in sealed
      envelopes, and all patients were randomly assigned, at recruitment, to the
      midazolam-meperidine combination (group-MM) or remifentanil alone (group-R). If a patient was
      excluded during the study, the following patient assumed the status of the excluded patient.

      Patients are allocated into one of two groups, Group 1 and Group 2 (27 patients each)
      according to the PIN at the recruitment.

      The exclusion criteria were as follows: refusal or inability to provide written informed
      consent, age <19 years, pregnancy, previous history of large bowel surgery, a psychiatric
      disorder, an addictions to opiates or sedatives, a previous history of adverse events to any
      drug used in the present study, and performance of any additional diagnostic procedure after
      completion of colonoscopy.

      All colonoscopic procedure is going to be performed by one Gastroenterologist (endoscopist).

      On arriving in the endoscopy room, supplemental oxygen (2 L/min) was given through the mouth
      and both nostrils via a specially designed nasal prong which could monitor the end-tidal CO2
      (ETCO2) level.

      Before drug administration, the basal values of mean blood pressure (MBP), heart rate (HR),
      peripheral O2 saturation (SpO2), respiratory rate (RR), end-expiratory CO2 level (ETCO2), and
      the bispectral index (BIS), were recorded by a single observer, who also monitored these
      values every 5 min during entire colonoscopy procedures.

      Supplemental oxygen (3 L/min) is given through nasal prong with capnography transducer in all
      patients.

      Two min before the colonoscopy procedure, a bolus midazolam of 0.03 mg/kg with a bolus
      meperidine of 1.0 mg/kg are given intravenously over 60 sec in Group 1 or those of comparable
      amount of diluted remifentanil 0.4 mcg/kg are given in Group 2 at the colonoscopy room, and a
      continuous infusion of diluted remifentanil of 0.04 mcg/kg/min is followed in Group 2 or that
      of comparable amount of normal saline (placebo) is followed in Group 1.

      The patients are asked to rate the degree of pain and distress (reverse satisfaction) by a
      100 mm Visual analogue scale (VAS; 0 = minimum, 100 = maximum) just after passing the scope,
      during the scope, just after the completion of the colonoscopy and at the discharge from the
      recovery unit.

      After colonoscopy, the patients are transferred to the recovery unit and evaluated every 5
      min until ready for discharge from the 30 min stay in the recovery unit.

      The patients are considered recovered if when they achieved an Aldrete score of 10 (Aldrete
      JA , Kroulik D . A postanesthetic recovery score. Anesth Analg 1970; 49: 924 - 34), have
      stable vital signs, are able to tolerate oral fluids, have no nausea, vomiting, or itching,
      and can walk unaided.

      Assessment of readiness to ambulate is made by a blinded observer who remained with the
      patient for the duration of recovery unit stay.

      The observer is instructed that the patients are required to walk as if they were leaving the
      recovery unit unescorted.

      Aldrete score, patient pain and satisfaction (distress score) were determined every 5 min
      during colonoscopy and after colonoscopy up to 30 min. Time for achieving Aldrete score 10,
      patient's degree of pain, patient's satisfaction during and after colonoscopy, patient's
      ability to recall the explanations and instructions given during and before colonoscopy are
      determined and compared.

      Aldrete score Respiration: Able to take deep breath and cough = 2, Dyspnea/shallow breathing
      = 1, Apnea = 0 O2 saturation: Maintains > 92% on room air =2, Needs O2 inhalation to maintain
      O2 saturation > 90% =1 , O2 saturation < 90% even with supplemental oxygen =0 Consciousness:
      Fully awake= 2, Arousable on calling = 1, Not responding = 0 Circulation: BP +/- 20 mm Hg
      preop =2, BP +/- 20-50 mm Hg preop =1, BP +/- 50 mm Hg preop =0 Activity: Able to move 4
      extremities = 2, Able to move 2 extremities = 1, Able to move 0 extremities = 0
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: The Recovery Time
time frame: every 5 minutes after completing colonoscopy up to 30 min
description: Time from completing the colonoscopy to achieving Aldrete score 10 in the recovery unit
Aldrete score
Respiration: Able to take deep breath and cough = 2, Dyspnea/shallow breathing = 1, Apnea = 0
O2 saturation: Maintains > 92% on room air =2, Needs O2 inhalation to maintain O2 saturation > 90% =1 , O2 saturation < 90% even with supplemental oxygen =0
Consciousness: Fully awake= 2, Arousable on calling = 1, Not responding = 0
Circulation: BP +/- 20 mm Hg preop =2, BP +/- 20-50 mm Hg preop =1, BP +/- 50 mm Hg preop =0
Activity: Able to move 4 extremities = 2, Able to move 2 extremities = 1, Able to move 0 extremities = 0
To estimate the required sample size, we conducted a pilot study to measure the recovery of 10 patients in each of groups-MM and -R before the present study. The means and standard deviations were 22.5 ± 9.5 and 7.5 ± 9.2 min respectively. We wished to be able to distinguish a difference of 7.5 min, thus half of the observed difference.
measure: Participants Assumed to Feel Frequent Pain
time frame: during and after colonoscopy
description: patients sound "Ah" at feeling pain during colonosocpy: if a patients sounds "Ah" > 6 times, the patient was assumed to feel frequent pain.
measure: Bispectra Lindex Score
time frame: every 5 min during and after colonoscopy
description: Bispectral index (BIS) score 0-100 maximal sedation=0, maximal sedation=100
measure: Patient's Distress Score
time frame: 5 min after the end of colonoscopy
description: patients' distress in visual analogue scale 100 mm minimal distress=0, maximal distress=100
measure: Endoscopist Satisfaction
time frame: 5 min after the colonoscopy
description: endoscopist's satisfaction after colonoscopy in visual analogue scale 100 mm
measure: Indigence of Patient's Recall
time frame: after colonoscopy
description: The numbers of patients who recalled instructions and explanations given during colonoscopy
arm group label: Remifentanil
arm group type: Experimental
description: remifentanil of 0.04 mcg/kg/min with placebo (for midazolam) and placebo (for meperidine)
arm group label: midazolam and meperidine
arm group type: Active Comparator
description: a bolus midazolam of 0.03 mg/kg a bolus meperidine of 1.0 mg/kg placebo (for remifentanil)
intervention type: Drug
intervention name: Remifentanil
description: continuous infusion 0.4 mcg/kg/min
arm group label: Remifentanil
other name: Ultiva
intervention type: Drug
intervention name: Midazolam
description: bolus injection
arm group label: midazolam and meperidine
other name: dormicum
intervention type: Drug
intervention name: Meperidine
description: bolus injection for 30 sec 1.0 mg/kg
arm group label: midazolam and meperidine
other name: Pethidine Injection
intervention type: Drug
intervention name: placebo (for remifentanil)
description: normal saline mimic diluted remifentanil
arm group label: midazolam and meperidine
other name: normal saline
intervention type: Drug
intervention name: placebo (for midazolam)
description: normal saline mimic to midazolam injection
arm group label: Remifentanil
other name: normal saline
intervention type: Drug
intervention name: placebo (for meperidine)
description: normal saline mimic meperidine injection
arm group label: Remifentanil
other name: normal saline
criteria: 
gender: All
minimum age: 19 Years
maximum age: 65 Years
healthy volunteers: No
last name: Tae-Yop Kim, MD, PhD
role: Principal Investigator
affiliation: Konkuk University
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Konkuk University Medical Center
investigator full name: Tae-Yop Kim, MD PhD
investigator title: Professor of Anesthesiology
mesh term: Midazolam
mesh term: Meperidine
mesh term: Remifentanil
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 