<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/NCT03240055</url>
  </required_header>
  <id_info>
    <org_study_id>mz2017</org_study_id>
    <nct_id>NCT03240055</nct_id>
  </id_info>
  <brief_title>The Effects of Spinal Anesthesia on ED50 and BIS50 of Etomidate for the Loss of Consciousness</brief_title>
  <acronym>LOC</acronym>
  <official_title>The Effects of Spinal Anesthesia on ED50 and BIS50 of Etomidate for the Loss of Consciousness</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>General Hospital of Ningxia Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>General Hospital of Ningxia Medical University</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>
      The purpose of this study is to investigate the effect of spinal anesthesia on ED50 and BIS50&#xD;
      of etomidate for the loss of consciousness (LOC) by using up-and-down method.The hypothesis&#xD;
      was that spinal anesthesia could significantly reduce the etomidate bolus dose for the LOC&#xD;
      and could also achieve hemodynamic stability during anesthesia induction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The combination of spinal with general anesthesia has been demonstrated to provide many&#xD;
      clinically relevant advantages, however, this technique often experiences hypotension and&#xD;
      bradycardia in the induction period of combined anesthesia. Etomidate is a carboxylated&#xD;
      imidazole-derived hypnotic, and it is the most cardiovascularly stable intravenous induction&#xD;
      drug, with the possible exception of ketamine. Meanwhile, the previous and our studies have&#xD;
      been reported that spinal anesthesia has a direct sedative effect on animals and humans, and&#xD;
      it markedly reduces the dose of hypnotic agents. To date, there is no dose-ranging study on&#xD;
      the effect of spinal anesthesia on dosage of etomidate for the loss of consciousness (LOC).&#xD;
      In the present study, investigators aim to investigate the effect of spinal anesthesia on the&#xD;
      median effective dose (ED50) and the BIS value (BIS50) of etomidate at which 50% of patients&#xD;
      lose consciousness compared to etomidate alone by using up-and-down method.&#xD;
&#xD;
      Patients were randomly allocated to one of two groups: only etomidate in group E (n=27) and&#xD;
      spinal anesthesia combined with etomidate in group SE (n=21) using a randomization table.&#xD;
      Patients in the SE group received spinal anesthesia first, and bilateral sensory anesthesia&#xD;
      level was confirmed to remain at the T4-T6 level. After confirmation of the level of sensory&#xD;
      anesthesia, the administration of etomidate was conducted. The etomidate (Nhwa&#xD;
      Pharmaceutical, Jiangsu, China) starting dose of E group and SE group is 0.105 mg/kg and&#xD;
      0.089mg/kg, respectively. The dose of etomidate used for next patient was determined&#xD;
      according to the response of the previously tested patient using the up-and-down method. If&#xD;
      the patient lose consciousness, the dose of etomidate was reduced by one dose gradient for&#xD;
      the next patient, and if didn't lose consciousness, the dose of etomidate was increased by&#xD;
      one dose gradient (one dose gradient is r=1:0.85, that is, the ratio of high dose/low dose&#xD;
      which are adjacent two doses). The testing of different dose levels of etomidate continued on&#xD;
      consecutive randomised patients until a sample size of seven crossover points from&#xD;
      &quot;conscious&quot; to &quot;LOC&quot; was reached&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2017</start_date>
  <completion_date type="Actual">July 15, 2017</completion_date>
  <primary_completion_date type="Actual">July 15, 2017</primary_completion_date>
  <phase>N/A</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>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Median effective dose (ED50)of etomidate at which 50% of patients lose consciousness</measure>
    <time_frame>After etomidate administration to the lowest BIS value appears，usually about 4 minutes</time_frame>
    <description>We want to determine Median effective dose (ED50) of etomidate at which 50% of patients lose consciousness in the SE and E group, respectively. It is a value，like 0.105mg/kg. Patients were considered to be loss of consciousness if there Observer's Assessment of Alertness/Sedation (OAA/S) scores were 2,1,or 0.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>BIS value (BIS50) of etomidate at which 50% of patients lose consciousness</measure>
    <time_frame>After etomidate administration to the lowest BIS value appears，usually about 4 minutes</time_frame>
    <description>We want to determine BIS value (BIS50) of etomidate at which 50% of patients lose consciousness in the SE and E group, respectively. It is a unitless value，like 60. Patients were considered to be loss of consciousness if there Observer's Assessment of Alertness/Sedation (OAA/S) scores were 2,1,or 0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The change of Mean Arterial Pressure (MAP)</measure>
    <time_frame>Baseline, l min (T1), 2min (T2), 3min (T3), 5min (T5) after administration of etomidate</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The change of heart rate (HR)</measure>
    <time_frame>Baseline, l min (T1), 2min (T2), 3min (T3), 5min (T5) after administration of etomidate</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Dose-Response Relationship, Drug</condition>
  <arm_group>
    <arm_group_label>Group SE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>21 patients received spinal anesthesia first. After confirmation of the level (T4-T6) of the sensory anesthesia, the sequential administration of etomidate was conducted</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group E</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>27 patients without spinal anesthesia in this group received sequential administration of etomidate</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>spinal anesthesia</intervention_name>
    <description>The spinal puncture was performed with a 25 G Sprotte needle at the L3-4 or L2-3 interspinous space. Hyperbaric bupivacaine 0.5% (3 ml) was administered into the spinal space. Hyperbaric bupivacaine is obtained through the addition of glucose 10% (1ml) to bupivacaine 0.75% (2ml). Cerebrospinal fluid aspiration (0.1 ml) was done to confirm correct needle placement before and after spinal drug administration. Whereafter the patient was turned rapidly to the supine position, sensory anesthesia height was evaluated bilaterally using a pinprick test with the sharp tip of a safety pin every 1 min until 15 min after the initiation of the spinal anesthesia, bed tilting (upwards, horizontal, or downwards) was performed until bilateral sensory anesthesia level was confirmed to remain at the T4-T6 level</description>
    <arm_group_label>Group SE</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>etomidate</intervention_name>
    <description>receive etomidate only</description>
    <arm_group_label>Group E</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ASA physical status I-II&#xD;
&#xD;
          -  Body mass index (BMI) between 18.0 and 24.5 kg/m2&#xD;
&#xD;
          -  Undergoing short elective laparotomy procedures, hysteroscopic and vaginal operation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication to spinal anesthesia&#xD;
&#xD;
          -  Hearing loss&#xD;
&#xD;
          -  History of cardiovascular disease, psychiatric and central nervous system diseases&#xD;
&#xD;
          -  Hepatic or renal dysfunction&#xD;
&#xD;
          -  Severe diabetes or hyperkalemia&#xD;
&#xD;
          -  History of drug and alcohol abuse&#xD;
&#xD;
          -  An allergy to amide local anesthetics or etomidate&#xD;
&#xD;
          -  Adrenocortical hypofunction&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Li Ningkang</last_name>
    <role>Principal Investigator</role>
    <affiliation>General Hospital of Ningxia Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>General Hospital of Ningxia Medical University</name>
      <address>
        <city>Yinchuan</city>
        <state>Ningxia</state>
        <zip>750004</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>July 21, 2017</study_first_submitted>
  <study_first_submitted_qc>August 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2017</study_first_posted>
  <last_update_submitted>September 2, 2017</last_update_submitted>
  <last_update_submitted_qc>September 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>spinal anesthesia</keyword>
  <keyword>etomidate</keyword>
  <keyword>median effective dose</keyword>
  <keyword>BIS50</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Unconsciousness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Etomidate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>safety</ipd_description>
  </patient_data>
  <!-- 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/NCT03240055
org study id: mz2017
nct id: NCT03240055
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to investigate the effect of spinal anesthesia on ED50 and BIS50
      of etomidate for the loss of consciousness (LOC) by using up-and-down method.The hypothesis
      was that spinal anesthesia could significantly reduce the etomidate bolus dose for the LOC
      and could also achieve hemodynamic stability during anesthesia induction.
The combination of spinal with general anesthesia has been demonstrated to provide many
      clinically relevant advantages, however, this technique often experiences hypotension and
      bradycardia in the induction period of combined anesthesia. Etomidate is a carboxylated
      imidazole-derived hypnotic, and it is the most cardiovascularly stable intravenous induction
      drug, with the possible exception of ketamine. Meanwhile, the previous and our studies have
      been reported that spinal anesthesia has a direct sedative effect on animals and humans, and
      it markedly reduces the dose of hypnotic agents. To date, there is no dose-ranging study on
      the effect of spinal anesthesia on dosage of etomidate for the loss of consciousness (LOC).
      In the present study, investigators aim to investigate the effect of spinal anesthesia on the
      median effective dose (ED50) and the BIS value (BIS50) of etomidate at which 50% of patients
      lose consciousness compared to etomidate alone by using up-and-down method.

      Patients were randomly allocated to one of two groups: only etomidate in group E (n=27) and
      spinal anesthesia combined with etomidate in group SE (n=21) using a randomization table.
      Patients in the SE group received spinal anesthesia first, and bilateral sensory anesthesia
      level was confirmed to remain at the T4-T6 level. After confirmation of the level of sensory
      anesthesia, the administration of etomidate was conducted. The etomidate (Nhwa
      Pharmaceutical, Jiangsu, China) starting dose of E group and SE group is 0.105 mg/kg and
      0.089mg/kg, respectively. The dose of etomidate used for next patient was determined
      according to the response of the previously tested patient using the up-and-down method. If
      the patient lose consciousness, the dose of etomidate was reduced by one dose gradient for
      the next patient, and if didn't lose consciousness, the dose of etomidate was increased by
      one dose gradient (one dose gradient is r=1:0.85, that is, the ratio of high dose/low dose
      which are adjacent two doses). The testing of different dose levels of etomidate continued on
      consecutive randomised patients until a sample size of seven crossover points from
      "conscious" to "LOC" was reached
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Median effective dose (ED50)of etomidate at which 50% of patients lose consciousness
time frame: After etomidate administration to the lowest BIS value appears，usually about 4 minutes
description: We want to determine Median effective dose (ED50) of etomidate at which 50% of patients lose consciousness in the SE and E group, respectively. It is a value，like 0.105mg/kg. Patients were considered to be loss of consciousness if there Observer's Assessment of Alertness/Sedation (OAA/S) scores were 2,1,or 0.
measure: BIS value (BIS50) of etomidate at which 50% of patients lose consciousness
time frame: After etomidate administration to the lowest BIS value appears，usually about 4 minutes
description: We want to determine BIS value (BIS50) of etomidate at which 50% of patients lose consciousness in the SE and E group, respectively. It is a unitless value，like 60. Patients were considered to be loss of consciousness if there Observer's Assessment of Alertness/Sedation (OAA/S) scores were 2,1,or 0.
measure: The change of Mean Arterial Pressure (MAP)
time frame: Baseline, l min (T1), 2min (T2), 3min (T3), 5min (T5) after administration of etomidate
measure: The change of heart rate (HR)
time frame: Baseline, l min (T1), 2min (T2), 3min (T3), 5min (T5) after administration of etomidate
arm group label: Group SE
arm group type: Experimental
description: 21 patients received spinal anesthesia first. After confirmation of the level (T4-T6) of the sensory anesthesia, the sequential administration of etomidate was conducted
arm group label: Group E
arm group type: Placebo Comparator
description: 27 patients without spinal anesthesia in this group received sequential administration of etomidate
intervention type: Drug
intervention name: spinal anesthesia
description: The spinal puncture was performed with a 25 G Sprotte needle at the L3-4 or L2-3 interspinous space. Hyperbaric bupivacaine 0.5% (3 ml) was administered into the spinal space. Hyperbaric bupivacaine is obtained through the addition of glucose 10% (1ml) to bupivacaine 0.75% (2ml). Cerebrospinal fluid aspiration (0.1 ml) was done to confirm correct needle placement before and after spinal drug administration. Whereafter the patient was turned rapidly to the supine position, sensory anesthesia height was evaluated bilaterally using a pinprick test with the sharp tip of a safety pin every 1 min until 15 min after the initiation of the spinal anesthesia, bed tilting (upwards, horizontal, or downwards) was performed until bilateral sensory anesthesia level was confirmed to remain at the T4-T6 level
arm group label: Group SE
intervention type: Other
intervention name: etomidate
description: receive etomidate only
arm group label: Group E
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Li Ningkang
role: Principal Investigator
affiliation: General Hospital of Ningxia Medical University
facility: 
country: China
responsible party type: Sponsor
mesh term: Unconsciousness
mesh term: Etomidate
sharing ipd: No
ipd description: safety