<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/NCT03810391</url>
  </required_header>
  <id_info>
    <org_study_id>Effect of butorphanol</org_study_id>
    <nct_id>NCT03810391</nct_id>
  </id_info>
  <brief_title>Using Preoperative Anxiety Score to Determine the Total Dose of Butorphanol for Sedation</brief_title>
  <official_title>Using Preoperative Anxiety Score to Determine the Total Dose of Butorphanol for Sedation in Patients Undergoing Lower Limb Orthopedic Procedures: A Randomized, Double-blind, Placebo-controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shengjing Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shengjing Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Orthopedic surgeries are considered to be discomfortable and the sense of fear and anxiety of&#xD;
      patients who already have preoperative anxiety may be aggravated by intraoperative&#xD;
      stimulation, which may contribute to postoperative complications. Previous studies have found&#xD;
      that high anxiety predicts increased sedative requirements. Therefore, the investigators&#xD;
      explored the relationship between anxiety and intraoperative butorphanol requirements and the&#xD;
      investigators evaluated the specific sedative requirement which can keep satisfactory&#xD;
      sedative state for patients by preoperative anxiety score&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of one hundred and eighteen patients who were to undergoing lower limb orthopedic&#xD;
      procedures with spinal anesthesia were selected，the Amsterdam preoperative anxiety and&#xD;
      information scale was used to evaluated the degree of preoperative anxiety one day before the&#xD;
      surgery. Patients in preoperative anxiety group were randomly allocated to two groups:&#xD;
      butorphanol group (Group A) and physiological saline group (Group B); Patients in&#xD;
      non-preoperative anxiety group were also randomly allocated to two groups: butorphanol group&#xD;
      (Group C) and physiological saline group (Group D). In Group A and Group C, patients received&#xD;
      an intravenous loading dose of 15ug/kg butorphanol 5 min before starting the surgery, then&#xD;
      followed by infusion of 7.5ug/kg/h butorphanol and stopped infusion until the Ramsay sedation&#xD;
      score reached 4 points, Group B and Group D received an infusion of the same volume of&#xD;
      physiological saline. The sedation scores were recorded 10 min after getting into the&#xD;
      operation room and 5, 10, 15, 30min after infusion of butorphanol or physiological saline.&#xD;
      The duration when Ramsay sedation score reached 4 points in Group A and C, adverse events and&#xD;
      post-operative visual analgesia scale scores were also recorded and compared.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2017</start_date>
  <completion_date type="Actual">December 31, 2018</completion_date>
  <primary_completion_date type="Actual">December 20, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>the Amsterdam preoperative anxiety and information scale was used to evaluated the degree of preoperative anxiety one day before the surgery. Patients in preoperative anxiety group were randomly allocated to two groups: butorphanol group (Group A) and physiological saline group (Group B); Patients in non-preoperative anxiety group were also randomly allocated to two groups: butorphanol group (Group C) and physiological saline group (Group D) In Group A and Group C, patients received an intravenous loading dose of 15ug/kg butorphanol 5 mins before starting the surgery, then followed by infusion of 7.5ug/kg/h butorphanol and stopped infusion when the Ramsay sedation score (RSS) reached 4 , Group B and Group D received an infusion of the same volume of physiological saline</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>preoperative anxiety score (Amsterdam preoperative anxiety and information scale, APAIS)</measure>
    <time_frame>one day before the surgery</time_frame>
    <description>evaluate the preoperative anxiety score one day before the surgery, the scale ranges from 0-33. And we define a score of 11 as a cut-off point, the higher the score the more serious the preoperative anxiety is</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ramsay sedation score (Ramsay sedation scale, RSS)</measure>
    <time_frame>during the surgery</time_frame>
    <description>evaluate the Ramsay sedation score 10 min after getting into the operation room and 5, 10, 15, 30min after infusion. The Ramsay sedation scale ranges from 1-6. 1, anxious and agitated or restless or both; 2, cooperative, orientated, and tranquil; 3, responds to commands only; 4, brisk response to a light glabellar tap or auditory stimulus; 5, sluggish response to a light glabellar tap or auditory stimulus; and 6, no response to a light glabellar tap or auditory stimulus. A sedative state with RSS 4 was considered as an adequate level of sedation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>the time when Ramsay sedation score reached 4 points</measure>
    <time_frame>Ramsay sedation score reach 4 points during the surgery</time_frame>
    <description>record the time when Ramsay sedation score reached 4 points. The Ramsay sedation scale ranges from 1-6. 1, anxious and agitated or restless or both; 2, cooperative, orientated, and tranquil; 3, responds to commands only; 4, brisk response to a light glabellar tap or auditory stimulus; 5, sluggish response to a light glabellar tap or auditory stimulus; and 6, no response to a light glabellar tap or auditory stimulus. A sedative state with RSS 4 was considered as an adequate level of sedation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>vital signs</measure>
    <time_frame>during the surgery</time_frame>
    <description>Record Mean Arterial Pressure(MAP)10 min after getting into the operation room and 5, 10, 15, 30min after infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of nausea/ vomiting, dizzy, bradycardia and hypotension</measure>
    <time_frame>in the first day after the surgery</time_frame>
    <description>Investigate the incidence of nausea/ vomiting, dizzy, bradycardia and hypotension in the first day after the surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>post-operative visual analgesia scale scores (VAS)</measure>
    <time_frame>within 24 hours after the surgery</time_frame>
    <description>investigate the VAS every hour till 6 hours and then every 2 hours till 24 hours. The VAS ranges from 1-10. 0 means painless; 1-3 means mild pain; 4-6 means moderate pain and 7-10 means severe pain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vital signs</measure>
    <time_frame>during the surgery</time_frame>
    <description>Record Spo2 10 min after getting into the operation room and 5, 10, 15, 30min after infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vital signs</measure>
    <time_frame>during the surgery</time_frame>
    <description>Record Heart Rate(HR) 10 min after getting into the operation room and 5, 10, 15, 30min after infusion</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">126</enrollment>
  <condition>Preoperative Anxiety Score</condition>
  <condition>Total Dose of Butorphanol</condition>
  <arm_group>
    <arm_group_label>preoperative anxiety and butorphanol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>preoperative anxiety scores of patients in Group A were &gt;11 and received an intravenous loading dose of 15ug/kg butorphanol 5 min before starting the surgery, then followed by infusion of 7.5ug/kg/h butorphanol and stopped infusion until the Ramsay sedation score reached 4 points</description>
  </arm_group>
  <arm_group>
    <arm_group_label>preoperative anxiety and saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>preoperative anxiety scores of patients in Group B were &gt;11 and received an infusion of the same volume of physiological saline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-preoperative anxiety and butorphanol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>preoperative anxiety scores of patients in Group C were ≤ 11 and received an intravenous loading dose of 15ug/kg butorphanol 5 min before starting the surgery, then followed by infusion of 7.5ug/kg/h butorphanol and stopped infusion until the Ramsay sedation score reached 4 points</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-preoperative anxiety and saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>preoperative anxiety scores of patients in Group D were ≤11 and received an infusion of the same volume of physiological saline</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Butorphanol</intervention_name>
    <description>intravenous loading dose of 15ug/kg butorphanol,and followed by infusion of 7.5ug/kg/h butorphanol and stopped infusion until the Ramsay sedation score reached 4 points</description>
    <arm_group_label>non-preoperative anxiety and butorphanol</arm_group_label>
    <arm_group_label>preoperative anxiety and butorphanol</arm_group_label>
    <other_name>butorphanol tartrate injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>physiological saline</intervention_name>
    <description>intravenous infusion of the same volume of physiological saline</description>
    <arm_group_label>non-preoperative anxiety and saline</arm_group_label>
    <arm_group_label>preoperative anxiety and saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  American Society of Anesthesiologists (ASA)Ⅰ-Ⅱ&#xD;
&#xD;
          -  18-75 years&#xD;
&#xD;
          -  Scheduled for elective low limb orthopaedic procedures under spinal anesthesia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  central system disease&#xD;
&#xD;
          -  cardiovascular disease&#xD;
&#xD;
          -  autonomic nervous system disease&#xD;
&#xD;
          -  long term use of analgesic, sedative, and anti-anxiety drugs&#xD;
&#xD;
          -  psychosis&#xD;
&#xD;
          -  a patient with a language communication disorder not willing to cooperate with the&#xD;
             experimenter&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Junchao Zhu, professor</last_name>
    <role>Study Director</role>
    <affiliation>Shengjing Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>shengjing hospital of China medical university</name>
      <address>
        <city>Shenyang</city>
        <state>Liao Ning</state>
        <zip>110004</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 13, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>January 17, 2019</last_update_submitted>
  <last_update_submitted_qc>January 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shengjing Hospital</investigator_affiliation>
    <investigator_full_name>Yanchao Yang</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Butorphanol</keyword>
  <keyword>preoperative anxiety</keyword>
  <keyword>sedation</keyword>
  <keyword>recommend dose</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anxiety Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Butorphanol</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03810391
org study id: Effect of butorphanol
nct id: NCT03810391
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Orthopedic surgeries are considered to be discomfortable and the sense of fear and anxiety of
      patients who already have preoperative anxiety may be aggravated by intraoperative
      stimulation, which may contribute to postoperative complications. Previous studies have found
      that high anxiety predicts increased sedative requirements. Therefore, the investigators
      explored the relationship between anxiety and intraoperative butorphanol requirements and the
      investigators evaluated the specific sedative requirement which can keep satisfactory
      sedative state for patients by preoperative anxiety score
A total of one hundred and eighteen patients who were to undergoing lower limb orthopedic
      procedures with spinal anesthesia were selected，the Amsterdam preoperative anxiety and
      information scale was used to evaluated the degree of preoperative anxiety one day before the
      surgery. Patients in preoperative anxiety group were randomly allocated to two groups:
      butorphanol group (Group A) and physiological saline group (Group B); Patients in
      non-preoperative anxiety group were also randomly allocated to two groups: butorphanol group
      (Group C) and physiological saline group (Group D). In Group A and Group C, patients received
      an intravenous loading dose of 15ug/kg butorphanol 5 min before starting the surgery, then
      followed by infusion of 7.5ug/kg/h butorphanol and stopped infusion until the Ramsay sedation
      score reached 4 points, Group B and Group D received an infusion of the same volume of
      physiological saline. The sedation scores were recorded 10 min after getting into the
      operation room and 5, 10, 15, 30min after infusion of butorphanol or physiological saline.
      The duration when Ramsay sedation score reached 4 points in Group A and C, adverse events and
      post-operative visual analgesia scale scores were also recorded and compared.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: the Amsterdam preoperative anxiety and information scale was used to evaluated the degree of preoperative anxiety one day before the surgery. Patients in preoperative anxiety group were randomly allocated to two groups: butorphanol group (Group A) and physiological saline group (Group B); Patients in non-preoperative anxiety group were also randomly allocated to two groups: butorphanol group (Group C) and physiological saline group (Group D) In Group A and Group C, patients received an intravenous loading dose of 15ug/kg butorphanol 5 mins before starting the surgery, then followed by infusion of 7.5ug/kg/h butorphanol and stopped infusion when the Ramsay sedation score (RSS) reached 4 , Group B and Group D received an infusion of the same volume of physiological saline
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: preoperative anxiety score (Amsterdam preoperative anxiety and information scale, APAIS)
time frame: one day before the surgery
description: evaluate the preoperative anxiety score one day before the surgery, the scale ranges from 0-33. And we define a score of 11 as a cut-off point, the higher the score the more serious the preoperative anxiety is
measure: Ramsay sedation score (Ramsay sedation scale, RSS)
time frame: during the surgery
description: evaluate the Ramsay sedation score 10 min after getting into the operation room and 5, 10, 15, 30min after infusion. The Ramsay sedation scale ranges from 1-6. 1, anxious and agitated or restless or both; 2, cooperative, orientated, and tranquil; 3, responds to commands only; 4, brisk response to a light glabellar tap or auditory stimulus; 5, sluggish response to a light glabellar tap or auditory stimulus; and 6, no response to a light glabellar tap or auditory stimulus. A sedative state with RSS 4 was considered as an adequate level of sedation
measure: the time when Ramsay sedation score reached 4 points
time frame: Ramsay sedation score reach 4 points during the surgery
description: record the time when Ramsay sedation score reached 4 points. The Ramsay sedation scale ranges from 1-6. 1, anxious and agitated or restless or both; 2, cooperative, orientated, and tranquil; 3, responds to commands only; 4, brisk response to a light glabellar tap or auditory stimulus; 5, sluggish response to a light glabellar tap or auditory stimulus; and 6, no response to a light glabellar tap or auditory stimulus. A sedative state with RSS 4 was considered as an adequate level of sedation
measure: vital signs
time frame: during the surgery
description: Record Mean Arterial Pressure(MAP)10 min after getting into the operation room and 5, 10, 15, 30min after infusion
measure: The incidence of nausea/ vomiting, dizzy, bradycardia and hypotension
time frame: in the first day after the surgery
description: Investigate the incidence of nausea/ vomiting, dizzy, bradycardia and hypotension in the first day after the surgery
measure: post-operative visual analgesia scale scores (VAS)
time frame: within 24 hours after the surgery
description: investigate the VAS every hour till 6 hours and then every 2 hours till 24 hours. The VAS ranges from 1-10. 0 means painless; 1-3 means mild pain; 4-6 means moderate pain and 7-10 means severe pain
measure: Vital signs
time frame: during the surgery
description: Record Spo2 10 min after getting into the operation room and 5, 10, 15, 30min after infusion
measure: Vital signs
time frame: during the surgery
description: Record Heart Rate(HR) 10 min after getting into the operation room and 5, 10, 15, 30min after infusion
arm group label: preoperative anxiety and butorphanol
arm group type: Experimental
description: preoperative anxiety scores of patients in Group A were >11 and received an intravenous loading dose of 15ug/kg butorphanol 5 min before starting the surgery, then followed by infusion of 7.5ug/kg/h butorphanol and stopped infusion until the Ramsay sedation score reached 4 points
arm group label: preoperative anxiety and saline
arm group type: Placebo Comparator
description: preoperative anxiety scores of patients in Group B were >11 and received an infusion of the same volume of physiological saline
arm group label: non-preoperative anxiety and butorphanol
arm group type: Experimental
description: preoperative anxiety scores of patients in Group C were ≤ 11 and received an intravenous loading dose of 15ug/kg butorphanol 5 min before starting the surgery, then followed by infusion of 7.5ug/kg/h butorphanol and stopped infusion until the Ramsay sedation score reached 4 points
arm group label: non-preoperative anxiety and saline
arm group type: Placebo Comparator
description: preoperative anxiety scores of patients in Group D were ≤11 and received an infusion of the same volume of physiological saline
intervention type: Drug
intervention name: Butorphanol
description: intravenous loading dose of 15ug/kg butorphanol,and followed by infusion of 7.5ug/kg/h butorphanol and stopped infusion until the Ramsay sedation score reached 4 points
arm group label: non-preoperative anxiety and butorphanol
arm group label: preoperative anxiety and butorphanol
other name: butorphanol tartrate injection
intervention type: Other
intervention name: physiological saline
description: intravenous infusion of the same volume of physiological saline
arm group label: non-preoperative anxiety and saline
arm group label: preoperative anxiety and saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Junchao Zhu, professor
role: Study Director
affiliation: Shengjing Hospital
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shengjing Hospital
investigator full name: Yanchao Yang
investigator title: Principal Investigator
mesh term: Anxiety Disorders
mesh term: Butorphanol