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/NCT06026566</url>
    </required_header>
    <id_info>
      <org_study_id>TongjiHospital-Anes QQ01</org_study_id>
      <nct_id>NCT06026566</nct_id>
    </id_info>
    <brief_title>Compatible Effect of Remimazolam Besylate Combined With Afentanil for ATI</brief_title>
    <official_title>Compatible Dose Study and Effect Observation of Remimazolam Besylate Combined With Afentanil for Awake Endotracheal Intubation</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tongji Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Tongji 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>
        1. To study the pharmacokinetics between remimazolam besylate and alfentanil;&#xD;
  &#xD;
          2. To determine the optimal dosage of the two drugs in awake endotracheal intubation;&#xD;
  &#xD;
          3. To provide clinical guidance for awake endotracheal intubation.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Tracheal intubation is the most effective and reliable method to establish artificial airway,&#xD;
        which provides the best conditions for relieving airway obstruction, ensuring airway patency,&#xD;
        removing respiratory secretions, preventing aspiration, assisting or controlling breathing,&#xD;
        etc. Difficult airway management strategies must be adopted when patients are predicted to&#xD;
        have difficulties in mask ventilation, supraglottic airway device (SAD) placement, or&#xD;
        endotracheal intubation and front-of-neck airway (FONA) establishment. Awake tracheal&#xD;
        intubation (ATI) is one of the important methods.&#xD;
  &#xD;
        ATI refers to tracheal intubation while the patient is awake and breathing spontaneously,&#xD;
        most commonly by flexible bronchoscopy (FB) or video laryngoscopy (VL), which allows for&#xD;
        airway control prior to induction of general anesthesia. Thus, the potential risks and&#xD;
        consequences of difficulty in establishing the airway after anesthesia induction are avoided.&#xD;
        The safety of ATI is reflected in the guarantee of spontaneous breathing and intrinsic airway&#xD;
        tension of patients before tracheal tube insertion. The failure rate of ATI is only 1-2%, and&#xD;
        it rarely requires airway first aid or causes patient death.&#xD;
  &#xD;
        ATI is currently the safest technique for dealing with difficult airways, but it accounts for&#xD;
        only 0.2% of all tracheal intubation types in the UK. The reason is that ATI operators may be&#xD;
        under great physical, mental, and psychological stress, which may lead to poor performance&#xD;
        and increase the risk of complications, including failure. In addition, mechanical&#xD;
        stimulation of the airway in the awake state can cause coughing, nausea, restlessness and&#xD;
        other reactions to tracheal intubation, resulting in adverse consequences. Therefore, before&#xD;
        the effective implementation of ATI, anesthesiologists often choose to combine small doses of&#xD;
        analgesic and sedative drugs to achieve the minimum degree of sedation effect, so as to&#xD;
        reduce the anxiety and discomfort of patients and improve the tolerance of patients.&#xD;
  &#xD;
        Studies have shown that drugs such as fentanyl, remifentanil, midazolam, propofol and&#xD;
        dexmedetomidine can be used to assist ATI to improve patient satisfaction and reduce the risk&#xD;
        of excessive sedation and airway obstruction. However, these drugs have different degrees of&#xD;
        cardiovascular or respiratory adverse reactions, especially when used in large doses, which&#xD;
        increases the risk of hypoxemia, hypotension or bradycardia. ATI guidelines suggest that&#xD;
        excessive sedation is very dangerous for some patients, and it is recommended to use it with&#xD;
        caution, and a minimum degree of reversible sedation is preferred. Therefore, how to ensure&#xD;
        good sedation and analgesia and maintain normal spontaneous breathing is worthy of further&#xD;
        study.&#xD;
  &#xD;
        Remimazolam besylate is a new type of benzodiazepine, which is an ultra-short-acting&#xD;
        sedative/anesthetic drug. The mechanism is that by binding to benzodiazepine receptors, it&#xD;
        specifically acts on GABAA receptors, enhances GABAA receptor activity, and selectively&#xD;
        promotes extracellular chloride ions into cells, leading to hyperpolarization of cell&#xD;
        membrane resting potential and decreased excitability, thus inhibiting neuronal electrical&#xD;
        activity and producing sedative effect. And this effect can be specifically antagonized by&#xD;
        flumazenil. As an important member of opioid receptor agonist, 30s of alfentanil exerts its&#xD;
        drug effect, and its safety is far better than that of morphine. Alfentanil does not cause&#xD;
        severe respiratory depression in the therapeutic dose range, and can reduce the use of&#xD;
        sedative drugs when used in combination. In gastrointestinal endoscopy, hysteroscopy,&#xD;
        fiberoptic bronchoscopy and other procedures with spontaneous breathing, alfentanil alone or&#xD;
        in combination with benzodiazepines shows mild respiratory depression and high safety.&#xD;
  &#xD;
        The purpose of this study is to study the pharmacokinetics between remimazolam besylate and&#xD;
        alfentanil hydrochloride by response surface analysis, to determine the standard drug&#xD;
        concentration under spontaneous breathing, and to observe the clinical effect of awake&#xD;
        tracheal intubation under this concentration dose, to explore the best compatible dose range&#xD;
        of the two drugs, in order to provide a reference for clinical application in patients with&#xD;
        difficult airway.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">April 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">August 31, 2025</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>Crossover Assignment</intervention_model>
      <intervention_model_description>crisscross</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Participant)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Respiratory Rate</measure>
      <time_frame>During surgery</time_frame>
      <description>RR≤8bpm means respiratory rate decreased after the use of Remimazolam Besylate and Afentanil.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Tidal volume</measure>
      <time_frame>During surgery</time_frame>
      <description>Vt≤5ml/kg means tidal volume decreased after the use of Remimazolam Besylate and Afentanil.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Deep breathing</measure>
      <time_frame>During surgery</time_frame>
      <description>Breathing hard and deep, and then PetCO2≥55mmHg mean deep breathing after the use of Remimazolam Besylate and Afentanil.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Airway obstruction</measure>
      <time_frame>During surgery</time_frame>
      <description>Difficulty in ventilation means airway obstruction after the use of Remimazolam Besylate and Afentanil.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Oxygen saturation decreased</measure>
      <time_frame>During surgery</time_frame>
      <description>SpO2≤94% means oxyfen saturation decreased after the use of Remimazolam Besylate and Afentanil.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Airway status</measure>
      <time_frame>During surgery</time_frame>
      <description>Airway status evaluation during intubation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intubation response</measure>
      <time_frame>During surgery</time_frame>
      <description>Body movement response during intubation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>RASS score</measure>
      <time_frame>During surgery</time_frame>
      <description>Rass score evaluation during anesthesia induction (+4: Combative; +3: Very agitated; +2: Agitated; +1: Restless; 0: Alert and Calm; -1: Drowsy; -2: Light Sedation; -3: Moderate Sedation; -3: Moderate Sedation; -4: Deep Sedation; -5: Unarousable)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemodynamic assessments</measure>
      <time_frame>During surgery</time_frame>
      <description>Mean arterial blood pressure (MAP) ≤50mmHg or heart rate (HR) ≤45bpm indicates that this combination of anesthetic concentrations causes circulatory depression side effects and is recorded by &quot;1&quot;; otherwise, it is recorded by &quot;0&quot;.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The satisfaction of patients and anesthesiologists</measure>
      <time_frame>Up to 2 hours after surgery</time_frame>
      <description>The satisfaction of patients and anesthesiologists with the anesthesia regimen was evaluated (very satisfied, satisfied, fair, dissatisfied, very dissatisfied).</description>
    </secondary_outcome>
    <number_of_arms>6</number_of_arms>
    <enrollment type="Anticipated">180</enrollment>
    <condition>Remimazolam</condition>
    <condition>Awake Endotracheal Intubation</condition>
    <arm_group>
      <arm_group_label>Dos of R 0.1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The dosage of Remimazolam Besylate is 0.1 mg/kg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dos of R 0.15</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The dosage of Remimazolam Besylate is 0.15 mg/kg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dos of R 0.2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The dosage of Remimazolam Besylate is 0.2 mg/kg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dos of R 0.25</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The dosage of Remimazolam Besylate is 0.25 mg/kg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dos of R 0.3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The dosage of Remimazolam Besylate is 0.3 mg/kg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dos of R 0.35</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The dosage of Remimazolam Besylate is 0.25 mg/kg</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dos of Afentanil 20</intervention_name>
      <description>the dosage of Afentanil is 20 ng/ml for TCI</description>
      <arm_group_label>Dos of R 0.3</arm_group_label>
      <arm_group_label>Dos of R 0.35</arm_group_label>
      <other_name>Afentanil 20</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dos of Afentanil 30</intervention_name>
      <description>the dosage of Afentanil is 30 ng/ml for TCI</description>
      <arm_group_label>Dos of R 0.2</arm_group_label>
      <arm_group_label>Dos of R 0.25</arm_group_label>
      <arm_group_label>Dos of R 0.3</arm_group_label>
      <arm_group_label>Dos of R 0.35</arm_group_label>
      <other_name>Afentanil 30</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dos of Afentanil 40</intervention_name>
      <description>the dosage of Afentanil is 40 ng/ml for TCI</description>
      <arm_group_label>Dos of R 0.15</arm_group_label>
      <arm_group_label>Dos of R 0.2</arm_group_label>
      <arm_group_label>Dos of R 0.25</arm_group_label>
      <arm_group_label>Dos of R 0.3</arm_group_label>
      <arm_group_label>Dos of R 0.35</arm_group_label>
      <other_name>Afentanil 40</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dos of Afentanil 50</intervention_name>
      <description>the dosage of Afentanil is 50 ng/ml for TCI</description>
      <arm_group_label>Dos of R 0.1</arm_group_label>
      <arm_group_label>Dos of R 0.15</arm_group_label>
      <arm_group_label>Dos of R 0.2</arm_group_label>
      <arm_group_label>Dos of R 0.25</arm_group_label>
      <arm_group_label>Dos of R 0.3</arm_group_label>
      <arm_group_label>Dos of R 0.35</arm_group_label>
      <other_name>Afentanil 50</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dos of Afentanil 60</intervention_name>
      <description>the dosage of Afentanil is 60 ng/ml for TCI</description>
      <arm_group_label>Dos of R 0.1</arm_group_label>
      <arm_group_label>Dos of R 0.15</arm_group_label>
      <arm_group_label>Dos of R 0.2</arm_group_label>
      <arm_group_label>Dos of R 0.25</arm_group_label>
      <arm_group_label>Dos of R 0.3</arm_group_label>
      <arm_group_label>Dos of R 0.35</arm_group_label>
      <other_name>Afentanil 60</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dos of Afentanil 70</intervention_name>
      <description>the dosage of Afentanil is 70 ng/ml for TCI</description>
      <arm_group_label>Dos of R 0.1</arm_group_label>
      <arm_group_label>Dos of R 0.15</arm_group_label>
      <arm_group_label>Dos of R 0.2</arm_group_label>
      <arm_group_label>Dos of R 0.25</arm_group_label>
      <arm_group_label>Dos of R 0.3</arm_group_label>
      <arm_group_label>Dos of R 0.35</arm_group_label>
      <other_name>Afentanil 70</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dos of Afentanil 80</intervention_name>
      <description>the dosage of Afentanil is 80 ng/ml for TCI</description>
      <arm_group_label>Dos of R 0.1</arm_group_label>
      <arm_group_label>Dos of R 0.15</arm_group_label>
      <arm_group_label>Dos of R 0.2</arm_group_label>
      <arm_group_label>Dos of R 0.25</arm_group_label>
      <other_name>Afentanil 80</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dos of Afentanil 90</intervention_name>
      <description>the dosage of Afentanil is 90 ng/ml for TCI</description>
      <arm_group_label>Dos of R 0.1</arm_group_label>
      <arm_group_label>Dos of R 0.15</arm_group_label>
      <other_name>Afentanil 90</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dos of Afentanil 100</intervention_name>
      <description>the dosage of Afentanil is 100 ng/ml for TCI</description>
      <arm_group_label>Dos of R 0.1</arm_group_label>
      <other_name>Afentanil 100</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. no predictable difficult airway, Mallampati grade Ⅰ-II;&#xD;
  &#xD;
            2. deviation from ideal body weight ≤25%;&#xD;
  &#xD;
               [Ideal weight (kg) = height (cm) -100 (male) or 105 (female)]&#xD;
  &#xD;
            3. American Society of Anesthesiologists grade Ⅰ-II;&#xD;
  &#xD;
            4. Informed consent: voluntarily participate in the trial and sign the informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. patients with head and neck lesions (including malignant tumors, previous surgery or&#xD;
               radiotherapy), limited mouth opening, limited neck extension, obstructive sleep apnea,&#xD;
               morbid obesity, and progressive airway injury;&#xD;
  &#xD;
            2. Relative contraindications: patients with respiratory diseases, allergy to local&#xD;
               anesthetics, airway bleeding, and non-cooperation;&#xD;
  &#xD;
            3. patients known to be allergic to remimazolam besylate or benzodiazepines;&#xD;
  &#xD;
            4. patients with known allergy to alfentanil or opioids;&#xD;
  &#xD;
            5. body weight exceeding ±25% of ideal body weight;&#xD;
  &#xD;
            6. patients with coagulation dysfunction, endocrine diseases or other hemodynamic&#xD;
               conditions;&#xD;
  &#xD;
            7. patients with a history of drug or alcohol dependence;&#xD;
  &#xD;
            8. Subjects who were deemed unsuitable for the study by the investigators.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Qiaoqiao Xu</last_name>
      <role>Principal Investigator</role>
      <affiliation>Tongji Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Qiaoqiao Xu</last_name>
      <phone>+8618771006963</phone>
      <email>qiaoqiaoxu@aliyun.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Tongji Hospital, Tongji Medical College, Huazhong Science and Technology University</name>
        <address>
          <city>Wuhan</city>
          <state>Hubei</state>
          <zip>430030</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Qiaoqiao Xu</last_name>
        <phone>+8618771006963</phone>
        <email>qiaoqiaoxu@aliyun.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <results_reference>
      <citation>Bi SS, Deng CH, Zhou TY, Guan Z, Li L, Li HQ, Zhang LP, Yang L, Lu W. Remifentanil-sevoflurane interaction models of circulatory response to laryngoscopy and circulatory depression. Br J Anaesth. 2013 May;110(5):729-40. doi: 10.1093/bja/aes504. Epub 2013 Feb 6.</citation>
      <PMID>23388507</PMID>
    </results_reference>
    <results_reference>
      <citation>Ahmad I, El-Boghdadly K, Bhagrath R, Hodzovic I, McNarry AF, Mir F, O'Sullivan EP, Patel A, Stacey M, Vaughan D. Difficult Airway Society guidelines for awake tracheal intubation (ATI) in adults. Anaesthesia. 2020 Apr;75(4):509-528. doi: 10.1111/anae.14904. Epub 2019 Nov 14.</citation>
      <PMID>31729018</PMID>
    </results_reference>
    <results_reference>
      <citation>Ajay S, Singhania A, Akkara AG, Shah A, Adalja M. A study of flexible fiberoptic bronchoscopy aided tracheal intubation for patients undergoing elective surgery under general anesthesia. Indian J Otolaryngol Head Neck Surg. 2013 Apr;65(2):116-9. doi: 10.1007/s12070-012-0576-8. Epub 2012 Oct 17.</citation>
      <PMID>24427550</PMID>
    </results_reference>
    <results_reference>
      <citation>Cook TM. Strategies for the prevention of airway complications - a narrative review. Anaesthesia. 2018 Jan;73(1):93-111. doi: 10.1111/anae.14123.</citation>
      <PMID>29210033</PMID>
    </results_reference>
    <results_reference>
      <citation>El-Boghdadly K, Onwochei DN, Cuddihy J, Ahmad I. A prospective cohort study of awake fibreoptic intubation practice at a tertiary centre. Anaesthesia. 2017 Jun;72(6):694-703. doi: 10.1111/anae.13844.</citation>
      <PMID>28654138</PMID>
    </results_reference>
    <results_reference>
      <citation>Joseph TT, Gal JS, DeMaria S Jr, Lin HM, Levine AI, Hyman JB. A Retrospective Study of Success, Failure, and Time Needed to Perform Awake Intubation. Anesthesiology. 2016 Jul;125(1):105-14. doi: 10.1097/ALN.0000000000001140.</citation>
      <PMID>27111535</PMID>
    </results_reference>
    <results_reference>
      <citation>Law JA, Morris IR, Brousseau PA, de la Ronde S, Milne AD. The incidence, success rate, and complications of awake tracheal intubation in 1,554 patients over 12 years: an historical cohort study. Can J Anaesth. 2015 Jul;62(7):736-44. doi: 10.1007/s12630-015-0387-y. Epub 2015 Apr 24.</citation>
      <PMID>25907462</PMID>
    </results_reference>
    <results_reference>
      <citation>Alhomary M, Ramadan E, Curran E, Walsh SR. Videolaryngoscopy vs. fibreoptic bronchoscopy for awake tracheal intubation: a systematic review and meta-analysis. Anaesthesia. 2018 Sep;73(9):1151-1161. doi: 10.1111/anae.14299. Epub 2018 Apr 17.</citation>
      <PMID>29687891</PMID>
    </results_reference>
    <results_reference>
      <citation>Cook TM, Woodall N, Frerk C; Fourth National Audit Project. Major complications of airway management in the UK: results of the Fourth National Audit Project of the Royal College of Anaesthetists and the Difficult Airway Society. Part 1: anaesthesia. Br J Anaesth. 2011 May;106(5):617-31. doi: 10.1093/bja/aer058. Epub 2011 Mar 29.</citation>
      <PMID>21447488</PMID>
    </results_reference>
    <results_reference>
      <citation>Weinger MB, Vredenburgh AG, Schumann CM, Macario A, Williams KJ, Kalsher MJ, Smith B, Truong PC, Kim A. Quantitative description of the workload associated with airway management procedures. J Clin Anesth. 2000 Jun;12(4):273-82. doi: 10.1016/s0952-8180(00)00152-5.</citation>
      <PMID>10960198</PMID>
    </results_reference>
    <results_reference>
      <citation>Johnston KD, Rai MR. Conscious sedation for awake fibreoptic intubation: a review of the literature. Can J Anaesth. 2013 Jun;60(6):584-99. doi: 10.1007/s12630-013-9915-9. Epub 2013 Mar 20.</citation>
      <PMID>23512191</PMID>
    </results_reference>
    <results_reference>
      <citation>He XY, Cao JP, He Q, Shi XY. Dexmedetomidine for the management of awake fibreoptic intubation. Cochrane Database Syst Rev. 2014 Jan 19;2014(1):CD009798. doi: 10.1002/14651858.CD009798.pub2.</citation>
      <PMID>24442817</PMID>
    </results_reference>
    <results_reference>
      <citation>Moller IW, Krantz T, Wandall E, Kehlet H. Effect of alfentanil anaesthesia on the adrenocortical and hyperglycaemic response to abdominal surgery. Br J Anaesth. 1985 Jun;57(6):591-4. doi: 10.1093/bja/57.6.591.</citation>
      <PMID>3924084</PMID>
    </results_reference>
    <results_reference>
      <citation>Lin YJ, Wang YC, Huang HH, Huang CH, Liao MX, Lin PL. Target-controlled propofol infusion with or without bispectral index monitoring of sedation during advanced gastrointestinal endoscopy. J Gastroenterol Hepatol. 2020 Jul;35(7):1189-1195. doi: 10.1111/jgh.14943. Epub 2019 Dec 6.</citation>
      <PMID>31802534</PMID>
    </results_reference>
    <results_reference>
      <citation>Chiang MH, Wu SC, You CH, Wu KL, Chiu YC, Ma CW, Kao CW, Lin KC, Chen KH, Wang PC, Chou AK. Target-controlled infusion vs. manually controlled infusion of propofol with alfentanil for bidirectional endoscopy: a randomized controlled trial. Endoscopy. 2013 Nov;45(11):907-14. doi: 10.1055/s-0033-1344645. Epub 2013 Oct 28.</citation>
      <PMID>24165817</PMID>
    </results_reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Tongji Hospital</investigator_affiliation>
      <investigator_full_name>Qiaoqiao Xu</investigator_full_name>
      <investigator_title>Associate professor and deputy chief physician</investigator_title>
    </responsible_party>
    <keyword>Remimazolam</keyword>
    <keyword>Awake Endotracheal Intubation</keyword>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>To provide clinical application reference of the pharmacokinetics between remimazolam besylate and alfentanil for awake endotracheal intubation.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_time_frame>After completion of the study and publication of the article</ipd_time_frame>
    </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/NCT06026566
  org study id: TongjiHospital-Anes QQ01
  nct id: NCT06026566
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  1. To study the pharmacokinetics between remimazolam besylate and alfentanil;
  
          2. To determine the optimal dosage of the two drugs in awake endotracheal intubation;
  
          3. To provide clinical guidance for awake endotracheal intubation.
  Tracheal intubation is the most effective and reliable method to establish artificial airway,
        which provides the best conditions for relieving airway obstruction, ensuring airway patency,
        removing respiratory secretions, preventing aspiration, assisting or controlling breathing,
        etc. Difficult airway management strategies must be adopted when patients are predicted to
        have difficulties in mask ventilation, supraglottic airway device (SAD) placement, or
        endotracheal intubation and front-of-neck airway (FONA) establishment. Awake tracheal
        intubation (ATI) is one of the important methods.
  
        ATI refers to tracheal intubation while the patient is awake and breathing spontaneously,
        most commonly by flexible bronchoscopy (FB) or video laryngoscopy (VL), which allows for
        airway control prior to induction of general anesthesia. Thus, the potential risks and
        consequences of difficulty in establishing the airway after anesthesia induction are avoided.
        The safety of ATI is reflected in the guarantee of spontaneous breathing and intrinsic airway
        tension of patients before tracheal tube insertion. The failure rate of ATI is only 1-2%, and
        it rarely requires airway first aid or causes patient death.
  
        ATI is currently the safest technique for dealing with difficult airways, but it accounts for
        only 0.2% of all tracheal intubation types in the UK. The reason is that ATI operators may be
        under great physical, mental, and psychological stress, which may lead to poor performance
        and increase the risk of complications, including failure. In addition, mechanical
        stimulation of the airway in the awake state can cause coughing, nausea, restlessness and
        other reactions to tracheal intubation, resulting in adverse consequences. Therefore, before
        the effective implementation of ATI, anesthesiologists often choose to combine small doses of
        analgesic and sedative drugs to achieve the minimum degree of sedation effect, so as to
        reduce the anxiety and discomfort of patients and improve the tolerance of patients.
  
        Studies have shown that drugs such as fentanyl, remifentanil, midazolam, propofol and
        dexmedetomidine can be used to assist ATI to improve patient satisfaction and reduce the risk
        of excessive sedation and airway obstruction. However, these drugs have different degrees of
        cardiovascular or respiratory adverse reactions, especially when used in large doses, which
        increases the risk of hypoxemia, hypotension or bradycardia. ATI guidelines suggest that
        excessive sedation is very dangerous for some patients, and it is recommended to use it with
        caution, and a minimum degree of reversible sedation is preferred. Therefore, how to ensure
        good sedation and analgesia and maintain normal spontaneous breathing is worthy of further
        study.
  
        Remimazolam besylate is a new type of benzodiazepine, which is an ultra-short-acting
        sedative/anesthetic drug. The mechanism is that by binding to benzodiazepine receptors, it
        specifically acts on GABAA receptors, enhances GABAA receptor activity, and selectively
        promotes extracellular chloride ions into cells, leading to hyperpolarization of cell
        membrane resting potential and decreased excitability, thus inhibiting neuronal electrical
        activity and producing sedative effect. And this effect can be specifically antagonized by
        flumazenil. As an important member of opioid receptor agonist, 30s of alfentanil exerts its
        drug effect, and its safety is far better than that of morphine. Alfentanil does not cause
        severe respiratory depression in the therapeutic dose range, and can reduce the use of
        sedative drugs when used in combination. In gastrointestinal endoscopy, hysteroscopy,
        fiberoptic bronchoscopy and other procedures with spontaneous breathing, alfentanil alone or
        in combination with benzodiazepines shows mild respiratory depression and high safety.
  
        The purpose of this study is to study the pharmacokinetics between remimazolam besylate and
        alfentanil hydrochloride by response surface analysis, to determine the standard drug
        concentration under spontaneous breathing, and to observe the clinical effect of awake
        tracheal intubation under this concentration dose, to explore the best compatible dose range
        of the two drugs, in order to provide a reference for clinical application in patients with
        difficult airway.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: crisscross
  primary purpose: Treatment
  masking: Single (Participant)
  measure: Respiratory Rate
  time frame: During surgery
  description: RR≤8bpm means respiratory rate decreased after the use of Remimazolam Besylate and Afentanil.
  measure: Tidal volume
  time frame: During surgery
  description: Vt≤5ml/kg means tidal volume decreased after the use of Remimazolam Besylate and Afentanil.
  measure: Deep breathing
  time frame: During surgery
  description: Breathing hard and deep, and then PetCO2≥55mmHg mean deep breathing after the use of Remimazolam Besylate and Afentanil.
  measure: Airway obstruction
  time frame: During surgery
  description: Difficulty in ventilation means airway obstruction after the use of Remimazolam Besylate and Afentanil.
  measure: Oxygen saturation decreased
  time frame: During surgery
  description: SpO2≤94% means oxyfen saturation decreased after the use of Remimazolam Besylate and Afentanil.
  measure: Airway status
  time frame: During surgery
  description: Airway status evaluation during intubation
  measure: Intubation response
  time frame: During surgery
  description: Body movement response during intubation
  measure: RASS score
  time frame: During surgery
  description: Rass score evaluation during anesthesia induction (+4: Combative; +3: Very agitated; +2: Agitated; +1: Restless; 0: Alert and Calm; -1: Drowsy; -2: Light Sedation; -3: Moderate Sedation; -3: Moderate Sedation; -4: Deep Sedation; -5: Unarousable)
  measure: Hemodynamic assessments
  time frame: During surgery
  description: Mean arterial blood pressure (MAP) ≤50mmHg or heart rate (HR) ≤45bpm indicates that this combination of anesthetic concentrations causes circulatory depression side effects and is recorded by "1"; otherwise, it is recorded by "0".
  measure: The satisfaction of patients and anesthesiologists
  time frame: Up to 2 hours after surgery
  description: The satisfaction of patients and anesthesiologists with the anesthesia regimen was evaluated (very satisfied, satisfied, fair, dissatisfied, very dissatisfied).
  arm group label: Dos of R 0.1
  arm group type: Experimental
  description: The dosage of Remimazolam Besylate is 0.1 mg/kg
  arm group label: Dos of R 0.15
  arm group type: Experimental
  description: The dosage of Remimazolam Besylate is 0.15 mg/kg
  arm group label: Dos of R 0.2
  arm group type: Experimental
  description: The dosage of Remimazolam Besylate is 0.2 mg/kg
  arm group label: Dos of R 0.25
  arm group type: Experimental
  description: The dosage of Remimazolam Besylate is 0.25 mg/kg
  arm group label: Dos of R 0.3
  arm group type: Experimental
  description: The dosage of Remimazolam Besylate is 0.3 mg/kg
  arm group label: Dos of R 0.35
  arm group type: Experimental
  description: The dosage of Remimazolam Besylate is 0.25 mg/kg
  intervention type: Drug
  intervention name: Dos of Afentanil 20
  description: the dosage of Afentanil is 20 ng/ml for TCI
  arm group label: Dos of R 0.3
  arm group label: Dos of R 0.35
  other name: Afentanil 20
  intervention type: Drug
  intervention name: Dos of Afentanil 30
  description: the dosage of Afentanil is 30 ng/ml for TCI
  arm group label: Dos of R 0.2
  arm group label: Dos of R 0.25
  arm group label: Dos of R 0.3
  arm group label: Dos of R 0.35
  other name: Afentanil 30
  intervention type: Drug
  intervention name: Dos of Afentanil 40
  description: the dosage of Afentanil is 40 ng/ml for TCI
  arm group label: Dos of R 0.15
  arm group label: Dos of R 0.2
  arm group label: Dos of R 0.25
  arm group label: Dos of R 0.3
  arm group label: Dos of R 0.35
  other name: Afentanil 40
  intervention type: Drug
  intervention name: Dos of Afentanil 50
  description: the dosage of Afentanil is 50 ng/ml for TCI
  arm group label: Dos of R 0.1
  arm group label: Dos of R 0.15
  arm group label: Dos of R 0.2
  arm group label: Dos of R 0.25
  arm group label: Dos of R 0.3
  arm group label: Dos of R 0.35
  other name: Afentanil 50
  intervention type: Drug
  intervention name: Dos of Afentanil 60
  description: the dosage of Afentanil is 60 ng/ml for TCI
  arm group label: Dos of R 0.1
  arm group label: Dos of R 0.15
  arm group label: Dos of R 0.2
  arm group label: Dos of R 0.25
  arm group label: Dos of R 0.3
  arm group label: Dos of R 0.35
  other name: Afentanil 60
  intervention type: Drug
  intervention name: Dos of Afentanil 70
  description: the dosage of Afentanil is 70 ng/ml for TCI
  arm group label: Dos of R 0.1
  arm group label: Dos of R 0.15
  arm group label: Dos of R 0.2
  arm group label: Dos of R 0.25
  arm group label: Dos of R 0.3
  arm group label: Dos of R 0.35
  other name: Afentanil 70
  intervention type: Drug
  intervention name: Dos of Afentanil 80
  description: the dosage of Afentanil is 80 ng/ml for TCI
  arm group label: Dos of R 0.1
  arm group label: Dos of R 0.15
  arm group label: Dos of R 0.2
  arm group label: Dos of R 0.25
  other name: Afentanil 80
  intervention type: Drug
  intervention name: Dos of Afentanil 90
  description: the dosage of Afentanil is 90 ng/ml for TCI
  arm group label: Dos of R 0.1
  arm group label: Dos of R 0.15
  other name: Afentanil 90
  intervention type: Drug
  intervention name: Dos of Afentanil 100
  description: the dosage of Afentanil is 100 ng/ml for TCI
  arm group label: Dos of R 0.1
  other name: Afentanil 100
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Qiaoqiao Xu
  role: Principal Investigator
  affiliation: Tongji Hospital
  last name: Qiaoqiao Xu
  phone: +8618771006963
  email: qiaoqiaoxu@aliyun.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  citation: Bi SS, Deng CH, Zhou TY, Guan Z, Li L, Li HQ, Zhang LP, Yang L, Lu W. Remifentanil-sevoflurane interaction models of circulatory response to laryngoscopy and circulatory depression. Br J Anaesth. 2013 May;110(5):729-40. doi: 10.1093/bja/aes504. Epub 2013 Feb 6.
  PMID: 23388507
  citation: Ahmad I, El-Boghdadly K, Bhagrath R, Hodzovic I, McNarry AF, Mir F, O'Sullivan EP, Patel A, Stacey M, Vaughan D. Difficult Airway Society guidelines for awake tracheal intubation (ATI) in adults. Anaesthesia. 2020 Apr;75(4):509-528. doi: 10.1111/anae.14904. Epub 2019 Nov 14.
  PMID: 31729018
  citation: Ajay S, Singhania A, Akkara AG, Shah A, Adalja M. A study of flexible fiberoptic bronchoscopy aided tracheal intubation for patients undergoing elective surgery under general anesthesia. Indian J Otolaryngol Head Neck Surg. 2013 Apr;65(2):116-9. doi: 10.1007/s12070-012-0576-8. Epub 2012 Oct 17.
  PMID: 24427550
  citation: Cook TM. Strategies for the prevention of airway complications - a narrative review. Anaesthesia. 2018 Jan;73(1):93-111. doi: 10.1111/anae.14123.
  PMID: 29210033
  citation: El-Boghdadly K, Onwochei DN, Cuddihy J, Ahmad I. A prospective cohort study of awake fibreoptic intubation practice at a tertiary centre. Anaesthesia. 2017 Jun;72(6):694-703. doi: 10.1111/anae.13844.
  PMID: 28654138
  citation: Joseph TT, Gal JS, DeMaria S Jr, Lin HM, Levine AI, Hyman JB. A Retrospective Study of Success, Failure, and Time Needed to Perform Awake Intubation. Anesthesiology. 2016 Jul;125(1):105-14. doi: 10.1097/ALN.0000000000001140.
  PMID: 27111535
  citation: Law JA, Morris IR, Brousseau PA, de la Ronde S, Milne AD. The incidence, success rate, and complications of awake tracheal intubation in 1,554 patients over 12 years: an historical cohort study. Can J Anaesth. 2015 Jul;62(7):736-44. doi: 10.1007/s12630-015-0387-y. Epub 2015 Apr 24.
  PMID: 25907462
  citation: Alhomary M, Ramadan E, Curran E, Walsh SR. Videolaryngoscopy vs. fibreoptic bronchoscopy for awake tracheal intubation: a systematic review and meta-analysis. Anaesthesia. 2018 Sep;73(9):1151-1161. doi: 10.1111/anae.14299. Epub 2018 Apr 17.
  PMID: 29687891
  citation: Cook TM, Woodall N, Frerk C; Fourth National Audit Project. Major complications of airway management in the UK: results of the Fourth National Audit Project of the Royal College of Anaesthetists and the Difficult Airway Society. Part 1: anaesthesia. Br J Anaesth. 2011 May;106(5):617-31. doi: 10.1093/bja/aer058. Epub 2011 Mar 29.
  PMID: 21447488
  citation: Weinger MB, Vredenburgh AG, Schumann CM, Macario A, Williams KJ, Kalsher MJ, Smith B, Truong PC, Kim A. Quantitative description of the workload associated with airway management procedures. J Clin Anesth. 2000 Jun;12(4):273-82. doi: 10.1016/s0952-8180(00)00152-5.
  PMID: 10960198
  citation: Johnston KD, Rai MR. Conscious sedation for awake fibreoptic intubation: a review of the literature. Can J Anaesth. 2013 Jun;60(6):584-99. doi: 10.1007/s12630-013-9915-9. Epub 2013 Mar 20.
  PMID: 23512191
  citation: He XY, Cao JP, He Q, Shi XY. Dexmedetomidine for the management of awake fibreoptic intubation. Cochrane Database Syst Rev. 2014 Jan 19;2014(1):CD009798. doi: 10.1002/14651858.CD009798.pub2.
  PMID: 24442817
  citation: Moller IW, Krantz T, Wandall E, Kehlet H. Effect of alfentanil anaesthesia on the adrenocortical and hyperglycaemic response to abdominal surgery. Br J Anaesth. 1985 Jun;57(6):591-4. doi: 10.1093/bja/57.6.591.
  PMID: 3924084
  citation: Lin YJ, Wang YC, Huang HH, Huang CH, Liao MX, Lin PL. Target-controlled propofol infusion with or without bispectral index monitoring of sedation during advanced gastrointestinal endoscopy. J Gastroenterol Hepatol. 2020 Jul;35(7):1189-1195. doi: 10.1111/jgh.14943. Epub 2019 Dec 6.
  PMID: 31802534
  citation: Chiang MH, Wu SC, You CH, Wu KL, Chiu YC, Ma CW, Kao CW, Lin KC, Chen KH, Wang PC, Chou AK. Target-controlled infusion vs. manually controlled infusion of propofol with alfentanil for bidirectional endoscopy: a randomized controlled trial. Endoscopy. 2013 Nov;45(11):907-14. doi: 10.1055/s-0033-1344645. Epub 2013 Oct 28.
  PMID: 24165817
  responsible party type: Principal Investigator
  investigator affiliation: Tongji Hospital
  investigator full name: Qiaoqiao Xu
  investigator title: Associate professor and deputy chief physician
  sharing ipd: Yes
  ipd description: To provide clinical application reference of the pharmacokinetics between remimazolam besylate and alfentanil for awake endotracheal intubation.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd time frame: After completion of the study and publication of the article