xml: <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/NCT06018207</url>
    </required_header>
    <id_info>
      <org_study_id>2023ZSLYEC-402</org_study_id>
      <nct_id>NCT06018207</nct_id>
    </id_info>
    <brief_title>ED50 of Midazolam Oral Solution for Preoperative Hypnosis in Adults : An Up-and-Down Sequential Allocation Trial</brief_title>
    <acronym>ED50-MOS-PH</acronym>
    <official_title>The Median Effective Dose of Midazolam Oral Solution for Preoperative Hypnosis in Non-Elderly Adults in the Preoperative Room: An Up-and-Down Sequential Allocation Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sixth Affiliated Hospital, Sun Yat-sen University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sixth Affiliated Hospital, Sun Yat-sen 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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Due to sleep deficiency, patients with insomnia syndrome or sub-clinical insomnia syndrome&#xD;
        often undergo severe stress while waiting for surgery. Studies have reported that&#xD;
        preoperative hypnosis could reduce stress and promote recovery. Midazolam has been&#xD;
        recommended to patients who under severe stress for preoperative sedation and anti-anxiety.&#xD;
        However, midazolam for preoperative hypnosis monitored with polysomnography (PSG) has not&#xD;
        been studied. In this exploratory study, the median effective dose (ED50) and ED95 of&#xD;
        Midazolam Oral Solution for preoperative hypnosis in non-elderly adults using the gold&#xD;
        standard tool of PSG, will be explored by up-and-down sequential allocation and probit&#xD;
        method.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The exploratory study of ED50 will be manipulated by an up-and-down sequential allocation&#xD;
        with a single arm prospectively.&#xD;
  &#xD;
          1. The day before surgery, subjects will be enrolled according to the inclusion criteria&#xD;
             and sign the informed consent voluntarily.&#xD;
  &#xD;
          2. On the day of surgery, the clinical process is as follows. According to the routine&#xD;
             medical procedures of our center, patients should access in the operating room about 2&#xD;
             hours before their surgery for adequate preparation.After peripheral venous&#xD;
             catheterization, monitored by electrocardiogram, noninvasive blood pressure, and pulse&#xD;
             oxygen saturation, invasive procedures,such as arterial catheterization, central venous&#xD;
             catheterization or nerve blocks, will be operated individually according to surgical and&#xD;
             anesthesia necessity.&#xD;
  &#xD;
          3. The intervention of Midazolam Oral Solution for preoperative hypnosis will be done after&#xD;
             invasive procedures. The ED50 dose of midazolam oral solution for hypnosis is studied&#xD;
             using an up-and-down sequential allocation while waiting for surgery and general&#xD;
             anesthesia in preoperative room.&#xD;
  &#xD;
             The starting dose is 6 mg and the step size is 1 mg. The interval sequential dose is&#xD;
             varied by 1 mg based on the hypnosis response of the previous patient after one hour.&#xD;
             Sleep of the subjects will be monitored by portable PSG (Alice PDx).&#xD;
  &#xD;
             Definition of successful hypnosis by taking midazolam oral solution: The polysomnograph&#xD;
             (PSG) not only shows stage N2 within 30 minutes, but also shows stage N3 within an hour;&#xD;
             or else, definition of unsuccessful hypnosis. The intervention procedure : (1) The first&#xD;
             subject takes 6mg of midazolam oral solution; (2) If succeed, the second subject will&#xD;
             take 4mg; (3) If not succeed, the second subject will take 8mg; (4) Until seven sequence&#xD;
             reversal inflection points.&#xD;
  &#xD;
          4. Measures of safety assurance:&#xD;
  &#xD;
        (1)Monitoring: Electrocardiogram, blood pressure, pulse oxygen saturation, respiratory rate,&#xD;
        consciousness; (2)Monitors, negative pressure suction devices, oxygen inhalation devices,&#xD;
        ventilators, items needed for emergency airway establishment, first aid medications,&#xD;
        systemically trained anesthesiologists and nurses; (3)Emergencies include, but are not&#xD;
        limited to: vomiting, respiratory depression, and respiratory obstruction. If any of the&#xD;
        above events occur after intervention, the clinical procedures or emergency procedures will&#xD;
        be followed immediately.&#xD;
  &#xD;
        Statistics： Using the sequential and probit method to determine the median effective dose and&#xD;
        ED95. The sample size is considered adequate once 7 pairs of sequence reversals have been&#xD;
        reached. Based on the preliminary test analysis, it is anticipated that 40 subjects would be&#xD;
        required.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">December 2023</completion_date>
    <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>The Median Effective Dose (ED50) of Midazolam Oral Solution</measure>
      <time_frame>Within 1 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room</time_frame>
      <description>The Median Effective Dose (ED50) of Midazolam Oral Solution for Preoperative Hypnosis in Non-Elderly Adults in the Preoperative Room, using an up-and-down sequential allocation.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>ED95 of Midazolam Oral Solution for Preoperative Hypnosis in Non-Elderly Adults in the Preoperative Room</measure>
      <time_frame>Within 1 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room</time_frame>
      <description>ED95 of Midazolam Oral Solution for Preoperative Hypnosis in Non-Elderly Adults in the Preoperative Room, using an up-and-down sequential allocation and calculating by Probit method (probability unit regression).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Description of Proportions of stage N1 in different doses</measure>
      <time_frame>Within 1.5 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room</time_frame>
      <description>We speculate that the sleep structure is different with the different doses of Midazolam Oral Solution.&#xD;
  Description of Proportions of stage N1 in different doses. Data are expressed as percentages.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Description of Proportions of stage N2 in different doses</measure>
      <time_frame>Within 1.5 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room</time_frame>
      <description>We speculate that the sleep structure is different with the different doses of Midazolam Oral Solution.&#xD;
  Description of Proportions of stage N2 in different doses. Data are expressed as percentages.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Description of Proportions of stage N3 in different doses</measure>
      <time_frame>Within 1.5 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room</time_frame>
      <description>We speculate that the sleep structure is different with the different doses of Midazolam Oral Solution.&#xD;
  Description of Proportions of stage N3 in different doses. Data are expressed as percentages.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Description of Proportions of stage REM in different doses</measure>
      <time_frame>Within 1.5 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room</time_frame>
      <description>We speculate that the sleep structure is different with the different doses of Midazolam Oral Solution.&#xD;
  Description of Proportions of stage REM in different doses. Data are expressed as percentages.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Description of Sleep latency(min) in different doses</measure>
      <time_frame>Within 1 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room</time_frame>
      <description>Sleep latency(min): the time it takes from taking Midazolam Oral Solution to entering the N2 phase of sleep.&#xD;
  We speculate that sleep latency is different with the doses of Midazolam Oral Sulution.&#xD;
  Data are expressed as mean ± standard deviation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Description of anti-anxiety effects in different doses</measure>
      <time_frame>Within 1.5 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room</time_frame>
      <description>Description of the different anti-anxiety effects between those who reach the hypnotic end point and those who do not, using the Generalized Anxiety Disorder-2 (GAD-2) scale.&#xD;
  Data are expressed as mean ± standard deviation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Description of sedative effect in different doses</measure>
      <time_frame>Within 1.5 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room</time_frame>
      <description>Description of the different sedative effects between those who reach the hypnotic end point and those who do not, using Richmond Agitation and Sedation Scale (RASS).&#xD;
  Data are expressed as mean ± standard deviation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Description of satisfaction for preoperative hypnosis in different doses</measure>
      <time_frame>On postoperative day 1</time_frame>
      <description>Description of sleep satisfaction while waiting for surgery in the operating room after taking Midazolam Oral Solution, using Visual Analogue Scale（VAS）score (0-10 points).&#xD;
  Data are expressed as mean ± standard deviation.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Dose</condition>
    <condition>Midazolam</condition>
    <condition>Preoperative</condition>
    <arm_group>
      <arm_group_label>An Up-and-Down Sequential Allocation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>An Up-and-Down Sequential Allocation is that the dose is varied based on the hypnosis response of the previous patient after taking midazolam oral solution for 1 hour.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Midazolam oral solution</intervention_name>
      <description>The ED50 dose of midazolam oral solution for hypnosis is studied using an up-and-down sequential allocation while waiting for surgery and general anesthesia in preoperative room.&#xD;
  The starting dose is 6 mg and the step size is 1 mg. The interval sequential dose is varied by 1 mg based on the hypnosis response of the previous patient after one hour.&#xD;
  Definition of successful hypnosis by taking midazolam oral solution:&#xD;
  The polysomnograph (PSG) not only shows stage N2 within 30 minutes, but also shows stage N3 within an hour; or else, definition of unsuccessful hypnosis.&#xD;
  The procedure is as follows: (1) The first subject is given 6mg of midazolam oral solution; (2) If succeed, the second subject takes 4mg; (3) If not succeed, the second subject takes 8mg; (4) Until seven sequence reversal inflection points.</description>
      <arm_group_label>An Up-and-Down Sequential Allocation</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Signed of informed consent voluntarily;&#xD;
  &#xD;
            2. Native Chinese speaker;&#xD;
  &#xD;
            3. Age 18-60 years old, male or female;&#xD;
  &#xD;
            4. BMI 18-30 kg/m2;&#xD;
  &#xD;
            5. American Society of Anesthesiologists (ASA) grade 1 or 2, New York Heart Association&#xD;
               (NYHA) gradeⅠorⅡ;&#xD;
  &#xD;
            6. Non-emergency cancer resection surgery is planned in the next day;&#xD;
  &#xD;
            7. Insomnia syndrome or sub-clinical insomnia syndrome in the past 1 month.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Contraindications for Midazolam Oral Solution (According to the Instruction for&#xD;
               Midazolam Oral Solution);&#xD;
  &#xD;
            2. High risk of Obstructive Sleep Apnea Symptoms (Total score of STOP-Bang scale ≥3&#xD;
               points);&#xD;
  &#xD;
            3. Suspected dementia (Total score of Mini-Mental State Examination (MMSE) according to&#xD;
               years of education: 0 year≤19 points; 1~6 years≤22 points; above of 6 years≤26&#xD;
               points);&#xD;
  &#xD;
            4. Severe depressive symptom within two weeks (Total score of Patient Health&#xD;
               Questionnaire-9 (PHQ-9)≥15);&#xD;
  &#xD;
            5. History of Neurological and Psychiatric diseases (According to the electronic medical&#xD;
               record system);&#xD;
  &#xD;
            6. History of Chronic Obstructive Pulmonary Disease (According to the electronic medical&#xD;
               record system);&#xD;
  &#xD;
            7. History of Heart Failure (According to the electronic medical record system);&#xD;
  &#xD;
            8. Intestinal obstruction(The electronic medical record system records those who&#xD;
               currently have any type of intestinal obstruction);&#xD;
  &#xD;
            9. Liver and renal insufficiency;&#xD;
  &#xD;
           10. Have taken opioids or drugs that act on the central nervous system within one week;&#xD;
  &#xD;
           11. Take CYP3A4 isoenzyme inhibitors or inducers within one week (According to the&#xD;
               Instruction for Midazolam Oral Solution);&#xD;
  &#xD;
           12. Consume any alcoholic beverage within 24 hours;&#xD;
  &#xD;
           13. Substance abusers (including alcohol, drugs or addictive substances);&#xD;
  &#xD;
           14. Pregnant or lactating women;&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jin sanqing, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>the Sixth Affiliated Hospital, Sun Yat-sen University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jin sanqing, MD</last_name>
      <phone>0086-13719366863</phone>
      <email>jinsq@mail.sysu.edu.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Zhou yan, MD</last_name>
      <phone>0086-13632404420</phone>
      <email>zhouyan8@mail3.sysu.edu.cn</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>the Sixth Affiliated Hospital, Sun Yat-sen University</name>
        <address>
          <city>Guangzhou</city>
          <state>Guangdong</state>
          <zip>510655</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>August 24, 2023</last_update_submitted>
    <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 30, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Sixth Affiliated Hospital, Sun Yat-sen University</investigator_affiliation>
      <investigator_full_name>SanQing Jin</investigator_full_name>
      <investigator_title>professor</investigator_title>
    </responsible_party>
    <keyword>midazolam; sleep; ED50; ED95; preoperative room;adult</keyword>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Midazolam</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06018207
  org study id: 2023ZSLYEC-402
  nct id: NCT06018207
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Due to sleep deficiency, patients with insomnia syndrome or sub-clinical insomnia syndrome
        often undergo severe stress while waiting for surgery. Studies have reported that
        preoperative hypnosis could reduce stress and promote recovery. Midazolam has been
        recommended to patients who under severe stress for preoperative sedation and anti-anxiety.
        However, midazolam for preoperative hypnosis monitored with polysomnography (PSG) has not
        been studied. In this exploratory study, the median effective dose (ED50) and ED95 of
        Midazolam Oral Solution for preoperative hypnosis in non-elderly adults using the gold
        standard tool of PSG, will be explored by up-and-down sequential allocation and probit
        method.
  The exploratory study of ED50 will be manipulated by an up-and-down sequential allocation
        with a single arm prospectively.
  
          1. The day before surgery, subjects will be enrolled according to the inclusion criteria
             and sign the informed consent voluntarily.
  
          2. On the day of surgery, the clinical process is as follows. According to the routine
             medical procedures of our center, patients should access in the operating room about 2
             hours before their surgery for adequate preparation.After peripheral venous
             catheterization, monitored by electrocardiogram, noninvasive blood pressure, and pulse
             oxygen saturation, invasive procedures,such as arterial catheterization, central venous
             catheterization or nerve blocks, will be operated individually according to surgical and
             anesthesia necessity.
  
          3. The intervention of Midazolam Oral Solution for preoperative hypnosis will be done after
             invasive procedures. The ED50 dose of midazolam oral solution for hypnosis is studied
             using an up-and-down sequential allocation while waiting for surgery and general
             anesthesia in preoperative room.
  
             The starting dose is 6 mg and the step size is 1 mg. The interval sequential dose is
             varied by 1 mg based on the hypnosis response of the previous patient after one hour.
             Sleep of the subjects will be monitored by portable PSG (Alice PDx).
  
             Definition of successful hypnosis by taking midazolam oral solution: The polysomnograph
             (PSG) not only shows stage N2 within 30 minutes, but also shows stage N3 within an hour;
             or else, definition of unsuccessful hypnosis. The intervention procedure : (1) The first
             subject takes 6mg of midazolam oral solution; (2) If succeed, the second subject will
             take 4mg; (3) If not succeed, the second subject will take 8mg; (4) Until seven sequence
             reversal inflection points.
  
          4. Measures of safety assurance:
  
        (1)Monitoring: Electrocardiogram, blood pressure, pulse oxygen saturation, respiratory rate,
        consciousness; (2)Monitors, negative pressure suction devices, oxygen inhalation devices,
        ventilators, items needed for emergency airway establishment, first aid medications,
        systemically trained anesthesiologists and nurses; (3)Emergencies include, but are not
        limited to: vomiting, respiratory depression, and respiratory obstruction. If any of the
        above events occur after intervention, the clinical procedures or emergency procedures will
        be followed immediately.
  
        Statistics： Using the sequential and probit method to determine the median effective dose and
        ED95. The sample size is considered adequate once 7 pairs of sequence reversals have been
        reached. Based on the preliminary test analysis, it is anticipated that 40 subjects would be
        required.
  allocation: N/A
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: The Median Effective Dose (ED50) of Midazolam Oral Solution
  time frame: Within 1 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room
  description: The Median Effective Dose (ED50) of Midazolam Oral Solution for Preoperative Hypnosis in Non-Elderly Adults in the Preoperative Room, using an up-and-down sequential allocation.
  measure: ED95 of Midazolam Oral Solution for Preoperative Hypnosis in Non-Elderly Adults in the Preoperative Room
  time frame: Within 1 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room
  description: ED95 of Midazolam Oral Solution for Preoperative Hypnosis in Non-Elderly Adults in the Preoperative Room, using an up-and-down sequential allocation and calculating by Probit method (probability unit regression).
  measure: Description of Proportions of stage N1 in different doses
  time frame: Within 1.5 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room
  description: We speculate that the sleep structure is different with the different doses of Midazolam Oral Solution.
  Description of Proportions of stage N1 in different doses. Data are expressed as percentages.
  measure: Description of Proportions of stage N2 in different doses
  time frame: Within 1.5 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room
  description: We speculate that the sleep structure is different with the different doses of Midazolam Oral Solution.
  Description of Proportions of stage N2 in different doses. Data are expressed as percentages.
  measure: Description of Proportions of stage N3 in different doses
  time frame: Within 1.5 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room
  description: We speculate that the sleep structure is different with the different doses of Midazolam Oral Solution.
  Description of Proportions of stage N3 in different doses. Data are expressed as percentages.
  measure: Description of Proportions of stage REM in different doses
  time frame: Within 1.5 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room
  description: We speculate that the sleep structure is different with the different doses of Midazolam Oral Solution.
  Description of Proportions of stage REM in different doses. Data are expressed as percentages.
  measure: Description of Sleep latency(min) in different doses
  time frame: Within 1 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room
  description: Sleep latency(min): the time it takes from taking Midazolam Oral Solution to entering the N2 phase of sleep.
  We speculate that sleep latency is different with the doses of Midazolam Oral Sulution.
  Data are expressed as mean ± standard deviation.
  measure: Description of anti-anxiety effects in different doses
  time frame: Within 1.5 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room
  description: Description of the different anti-anxiety effects between those who reach the hypnotic end point and those who do not, using the Generalized Anxiety Disorder-2 (GAD-2) scale.
  Data are expressed as mean ± standard deviation.
  measure: Description of sedative effect in different doses
  time frame: Within 1.5 hour after taking Midazolam Oral Solution while waiting for surgery in the operating room
  description: Description of the different sedative effects between those who reach the hypnotic end point and those who do not, using Richmond Agitation and Sedation Scale (RASS).
  Data are expressed as mean ± standard deviation.
  measure: Description of satisfaction for preoperative hypnosis in different doses
  time frame: On postoperative day 1
  description: Description of sleep satisfaction while waiting for surgery in the operating room after taking Midazolam Oral Solution, using Visual Analogue Scale（VAS）score (0-10 points).
  Data are expressed as mean ± standard deviation.
  arm group label: An Up-and-Down Sequential Allocation
  arm group type: Experimental
  description: An Up-and-Down Sequential Allocation is that the dose is varied based on the hypnosis response of the previous patient after taking midazolam oral solution for 1 hour.
  intervention type: Drug
  intervention name: Midazolam oral solution
  description: The ED50 dose of midazolam oral solution for hypnosis is studied using an up-and-down sequential allocation while waiting for surgery and general anesthesia in preoperative room.
  The starting dose is 6 mg and the step size is 1 mg. The interval sequential dose is varied by 1 mg based on the hypnosis response of the previous patient after one hour.
  Definition of successful hypnosis by taking midazolam oral solution:
  The polysomnograph (PSG) not only shows stage N2 within 30 minutes, but also shows stage N3 within an hour; or else, definition of unsuccessful hypnosis.
  The procedure is as follows: (1) The first subject is given 6mg of midazolam oral solution; (2) If succeed, the second subject takes 4mg; (3) If not succeed, the second subject takes 8mg; (4) Until seven sequence reversal inflection points.
  arm group label: An Up-and-Down Sequential Allocation
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: No
  last name: Jin sanqing, MD
  role: Principal Investigator
  affiliation: the Sixth Affiliated Hospital, Sun Yat-sen University
  last name: Jin sanqing, MD
  phone: 0086-13719366863
  email: jinsq@mail.sysu.edu.cn
  last name: Zhou yan, MD
  phone: 0086-13632404420
  email: zhouyan8@mail3.sysu.edu.cn
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Sixth Affiliated Hospital, Sun Yat-sen University
  investigator full name: SanQing Jin
  investigator title: professor
  mesh term: Midazolam
  sharing ipd: No