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/NCT06009991</url>
    </required_header>
    <id_info>
      <org_study_id>TongjiHospital-Anes QQ02</org_study_id>
      <nct_id>NCT06009991</nct_id>
    </id_info>
    <brief_title>The Dose Range of Remimazolam Besylate in Different Age Groups</brief_title>
    <official_title>The Investigation of the Dose Range of Remimazolam Besylate in Different Age Groups of Adults and Its Effects on Hemodynamics</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tongji Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Renmin Hospital of Wuhan University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Wuhan University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>The General Hospital of Central Theater Command</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Taihe Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Yichang Central People's Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Jingzhou Central Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Beijing Shijitan Hospital, Capital Medical University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>First Affiliated Hospital of Fujian Medical University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Tianjin Nankai Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Sichuan Provincial People's Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Shanxi Bethune Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </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>
        This is a multicenter, randomized, parallel, controlled clinical study of patients at&#xD;
        different ages underwent elective non-cardiac surgery under general anesthesia. The aim of&#xD;
        this study is to explore the dose range of remimazolam besylate for patients at different&#xD;
        ages, to provide guidance for anesthesia induction and maintenance of remimazolam besylate.&#xD;
        And to investigate the incidence of perioperative hypotension and postoperative related organ&#xD;
        dysfunction in patients received total intravenous anesthesia with remimazolam besylate,&#xD;
        compared with propofol.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Surgery is an effective method to treat surgical diseases, prolong survival time and improve&#xD;
        the quality of life, but patients often face the risk of postoperative complications. In&#xD;
        general surgery patients, complications occur in more than 30% of patients. Several&#xD;
        observational studies have shown that the severity and duration of intraoperative hypotension&#xD;
        are significantly related to the risk of postoperative adverse events such as myocardial&#xD;
        injury, renal injury, stroke, delirium, prolonged hospitalization, and death.&#xD;
  &#xD;
        Hypotension, defined as a systolic blood pressure of less than 90 mmHg, a diastolic blood&#xD;
        pressure of less than 50 mmHg, or a 20% reduction in systolic blood pressure from baseline,&#xD;
        is common during anesthesia and surgery. More than a third of patients receiving propofol&#xD;
        sedation experience intraoperative hypotension events, and their duration and degree are&#xD;
        associated with harm during surgery.&#xD;
  &#xD;
        Remimazolam is a new ultra-short-acting sedative drug developed in recent years, which has a&#xD;
        similar structure to midazolam. However, compared with midazolam, remimazolam has the&#xD;
        advantages of faster onset, faster recovery, and higher safety. Compared with propofol,&#xD;
        remimazolam is noninferior in the success rate of sedation, while the incidence of adverse&#xD;
        events such as hypotension is lower. At present, remimazolam has completed phase III clinical&#xD;
        studies in many fields, such as colonoscopy, fiberoptic bronchoscopy, and general anesthesia&#xD;
        induction and maintenance, which have shown its safety and effectiveness. However, there may&#xD;
        be differences in hemodynamics and drug sensitivity among patients of different ages.&#xD;
        Compared with young patients, elderly patients have a higher risk of hypotension after&#xD;
        anesthesia induction. At present, there is a lack of clinical studies with large samples to&#xD;
        clarify the recommended dose of remimazolam for anesthesia induction and maintenance in&#xD;
        patients of all ages. The updated instructions for remimazolam besylate for injection on&#xD;
        March 28, 2022 also mention that remimazolam besylate is used as a sedative drug for general&#xD;
        anesthesia induction and maintenance, and the relevant dose reference is given. However, the&#xD;
        safety and effectiveness of patients over 65 years have not been confirmed. The precise&#xD;
        regulation of clinical use for patients of different ages and the optimization of drug dosage&#xD;
        during anesthesia induction and maintenance are the basis for ensuring the safety of clinical&#xD;
        medication at present., in order to maintain the stability of perioperative hemodynamics, and&#xD;
        prevent or reduce the occurrence of adverse cardiovascular events.&#xD;
  &#xD;
        This study aims to investigate the effect of remimazolam total intravenous anesthesia on&#xD;
        intraoperative hemodynamics and the drug requirement for patients of different ages, with&#xD;
        propofol as the control, and intraoperative hemodynamics as the main evaluation index, so as&#xD;
        to provide evidence for clinical application of remimazolam for elderly patients in&#xD;
        anesthesia induction and maintenance.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 17, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">September 30, 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>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Participant)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Occurrence of intraoperative hypotension</measure>
      <time_frame>Operation 1 day</time_frame>
      <description>Occurrence of intraoperative hypotension</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Intraoperative dosage of vasoactive drugs</measure>
      <time_frame>Operation 1 day</time_frame>
      <description>Intraoperative dosage of vasoactive drugs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anesthesia recovery</measure>
      <time_frame>Operation 1 day</time_frame>
      <description>Anesthesia recovery</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cognitive function assessment</measure>
      <time_frame>Operation 1 day</time_frame>
      <description>Cognitive function assessment in the anesthesia recovery room</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Major organ complications</measure>
      <time_frame>Within 30 days after surgery</time_frame>
      <description>The occurrence of major organ complications within 30 days after surgery</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hospital stay of patients</measure>
      <time_frame>With 30 days after surgery</time_frame>
      <description>Hospital stay of patients</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>30-day mortality after surgery</measure>
      <time_frame>30-day after surgery</time_frame>
      <description>30-day mortality after surgery</description>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">1876</enrollment>
    <condition>Remimazolam</condition>
    <condition>Anesthesia</condition>
    <arm_group>
      <arm_group_label>Age 45-64</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients aged 45 to 64 years</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Age 65-74</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients aged 65 to 74 years</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Age 75-84</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients aged 75 to 84 years</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Age over 75</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients aged over 85 years</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Remimazolam besylate</intervention_name>
      <description>Age 45-64: Remimazolam Besylate 0.3 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need).&#xD;
  Age over 65: Remimazolam Besylate 0.15 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need).</description>
      <arm_group_label>Age 45-64</arm_group_label>
      <arm_group_label>Age 65-74</arm_group_label>
      <arm_group_label>Age 75-84</arm_group_label>
      <arm_group_label>Age over 75</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Propofol</intervention_name>
      <description>Age 45-64: Propofol 3.0μg/ml TCI for anesthesia induction and 2.5-3.0μg/ml TCI for maintenance.&#xD;
  Age over 65: Propofol 1.5-2.5μg/ml TCI for anesthesia induction and 1.5-2.5μg/ml TCI for maintenance</description>
      <arm_group_label>Age 45-64</arm_group_label>
      <arm_group_label>Age 65-74</arm_group_label>
      <arm_group_label>Age 75-84</arm_group_label>
      <arm_group_label>Age over 75</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. age above 45 years old;&#xD;
  &#xD;
            2. American Society of Anesthesiologists grade Ⅰ-II;&#xD;
  &#xD;
            3. patients undergoing tracheal intubation or laryngeal mask airway surgery under general&#xD;
               anesthesia (intravenous anesthesia);&#xD;
  &#xD;
            4. Informed consent: patients voluntarily participated in the trial and signed the&#xD;
               informed consent form.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. patients with cardiac function grade 3 or above;&#xD;
  &#xD;
            2. difficult to observe the pupil size of head or neck surgery patients;&#xD;
  &#xD;
            3. patients with multimodal anesthesia such as nerve block or spinal anesthesia&#xD;
               compounded;&#xD;
  &#xD;
            4. patients known to be allergic to remimazolam besylate or benzodiazepines;&#xD;
  &#xD;
            5. major vascular surgery and the type of surgery that directly affects hemodynamics;&#xD;
  &#xD;
            6. patients with coagulation dysfunction, endocrine diseases or other hemodynamic&#xD;
               conditions;&#xD;
  &#xD;
            7. minor surgery (operation duration &lt;1 hour);&#xD;
  &#xD;
            8. surgery lasting more than 4 hours;&#xD;
  &#xD;
            9. emergency surgery;&#xD;
  &#xD;
           10. patients with a history of drug or alcohol dependence;&#xD;
  &#xD;
           11. Subjects deemed unsuitable for the study by the investigator.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>45 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Ailin Luo</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>ongji 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>Ghaferi AA, Birkmeyer JD, Dimick JB. Complications, failure to rescue, and mortality with major inpatient surgery in medicare patients. Ann Surg. 2009 Dec;250(6):1029-34. doi: 10.1097/sla.0b013e3181bef697.</citation>
      <PMID>19953723</PMID>
    </results_reference>
    <results_reference>
      <citation>Wesselink EM, Kappen TH, Torn HM, Slooter AJC, van Klei WA. Intraoperative hypotension and the risk of postoperative adverse outcomes: a systematic review. Br J Anaesth. 2018 Oct;121(4):706-721. doi: 10.1016/j.bja.2018.04.036. Epub 2018 Jun 20.</citation>
      <PMID>30236233</PMID>
    </results_reference>
    <results_reference>
      <citation>Mascha EJ, Yang D, Weiss S, Sessler DI. Intraoperative Mean Arterial Pressure Variability and 30-day Mortality in Patients Having Noncardiac Surgery. Anesthesiology. 2015 Jul;123(1):79-91. doi: 10.1097/ALN.0000000000000686.</citation>
      <PMID>25929547</PMID>
    </results_reference>
    <results_reference>
      <citation>Salmasi V, Maheshwari K, Yang D, Mascha EJ, Singh A, Sessler DI, Kurz A. Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A Retrospective Cohort Analysis. Anesthesiology. 2017 Jan;126(1):47-65. doi: 10.1097/ALN.0000000000001432.</citation>
      <PMID>27792044</PMID>
    </results_reference>
    <results_reference>
      <citation>Babazade R, Yilmaz HO, Zimmerman NM, Stocchi L, Gorgun E, Kessler H, Sessler DI, Kurz A, Turan A. Association Between Intraoperative Low Blood Pressure and Development of Surgical Site Infection After Colorectal Surgery: A Retrospective Cohort Study. Ann Surg. 2016 Dec;264(6):1058-1064. doi: 10.1097/SLA.0000000000001607.</citation>
      <PMID>26756765</PMID>
    </results_reference>
    <results_reference>
      <citation>Futier E, Lefrant JY, Guinot PG, Godet T, Lorne E, Cuvillon P, Bertran S, Leone M, Pastene B, Piriou V, Molliex S, Albanese J, Julia JM, Tavernier B, Imhoff E, Bazin JE, Constantin JM, Pereira B, Jaber S; INPRESS Study Group. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial. JAMA. 2017 Oct 10;318(14):1346-1357. doi: 10.1001/jama.2017.14172.</citation>
      <PMID>28973220</PMID>
    </results_reference>
    <results_reference>
      <citation>Hallqvist L, Granath F, Fored M, Bell M. Intraoperative Hypotension and Myocardial Infarction Development Among High-Risk Patients Undergoing Noncardiac Surgery: A Nested Case-Control Study. Anesth Analg. 2021 Jul 1;133(1):6-15. doi: 10.1213/ANE.0000000000005391.</citation>
      <PMID>33555690</PMID>
    </results_reference>
    <results_reference>
      <citation>Ahuja S, Mascha EJ, Yang D, Maheshwari K, Cohen B, Khanna AK, Ruetzler K, Turan A, Sessler DI. Associations of Intraoperative Radial Arterial Systolic, Diastolic, Mean, and Pulse Pressures with Myocardial and Acute Kidney Injury after Noncardiac Surgery: A Retrospective Cohort Analysis. Anesthesiology. 2020 Feb;132(2):291-306. doi: 10.1097/ALN.0000000000003048.</citation>
      <PMID>31939844</PMID>
    </results_reference>
    <results_reference>
      <citation>Sneyd JR, Absalom AR, Barends CRM, Jones JB. Hypotension during propofol sedation for colonoscopy: a retrospective exploratory analysis and meta-analysis. Br J Anaesth. 2022 Apr;128(4):610-622. doi: 10.1016/j.bja.2021.10.044. Epub 2021 Dec 13.</citation>
      <PMID>34916051</PMID>
    </results_reference>
    <results_reference>
      <citation>Chen SH, Yuan TM, Zhang J, Bai H, Tian M, Pan CX, Bao HG, Jin XJ, Ji FH, Zhong TD, Wang Q, Lv JR, Wang S, Li YJ, Yu YH, Luo AL, Li XK, Min S, Li L, Zou XH, Huang YG. Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non-inferiority, phase III trial. J Gastroenterol Hepatol. 2021 Feb;36(2):474-481. doi: 10.1111/jgh.15188. Epub 2020 Jul 24.</citation>
      <PMID>32677707</PMID>
    </results_reference>
    <results_reference>
      <citation>Rex DK, Bhandari R, Desta T, DeMicco MP, Schaeffer C, Etzkorn K, Barish CF, Pruitt R, Cash BD, Quirk D, Tiongco F, Sullivan S, Bernstein D. A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy. Gastrointest Endosc. 2018 Sep;88(3):427-437.e6. doi: 10.1016/j.gie.2018.04.2351. Epub 2018 Apr 30.</citation>
      <PMID>29723512</PMID>
    </results_reference>
    <results_reference>
      <citation>Pastis NJ, Yarmus LB, Schippers F, Ostroff R, Chen A, Akulian J, Wahidi M, Shojaee S, Tanner NT, Callahan SP, Feldman G, Lorch DG Jr, Ndukwu I, Pritchett MA, Silvestri GA; PAION Investigators. Safety and Efficacy of Remimazolam Compared With Placebo and Midazolam for Moderate Sedation During Bronchoscopy. Chest. 2019 Jan;155(1):137-146. doi: 10.1016/j.chest.2018.09.015. Epub 2018 Oct 4.</citation>
      <PMID>30292760</PMID>
    </results_reference>
    <results_reference>
      <citation>Doi M, Morita K, Takeda J, Sakamoto A, Yamakage M, Suzuki T. Efficacy and safety of remimazolam versus propofol for general anesthesia: a multicenter, single-blind, randomized, parallel-group, phase IIb/III trial. J Anesth. 2020 Aug;34(4):543-553. doi: 10.1007/s00540-020-02788-6. Epub 2020 May 16.</citation>
      <PMID>32417976</PMID>
    </results_reference>
    <results_reference>
      <citation>Doi M, Hirata N, Suzuki T, Morisaki H, Morimatsu H, Sakamoto A. Safety and efficacy of remimazolam in induction and maintenance of general anesthesia in high-risk surgical patients (ASA Class III): results of a multicenter, randomized, double-blind, parallel-group comparative trial. J Anesth. 2020 Aug;34(4):491-501. doi: 10.1007/s00540-020-02776-w. Epub 2020 Apr 17.</citation>
      <PMID>32303884</PMID>
    </results_reference>
    <results_reference>
      <citation>Chen B, Pang QY, An R, Liu HL. A systematic review of risk factors for postinduction hypotension in surgical patients undergoing general anesthesia. Eur Rev Med Pharmacol Sci. 2021 Nov;25(22):7044-7050. doi: 10.26355/eurrev_202111_27255.</citation>
      <PMID>34859868</PMID>
    </results_reference>
    <results_reference>
      <citation>Saugel B, Reese PC, Sessler DI, Burfeindt C, Nicklas JY, Pinnschmidt HO, Reuter DA, Sudfeld S. Automated Ambulatory Blood Pressure Measurements and Intraoperative Hypotension in Patients Having Noncardiac Surgery with General Anesthesia: A Prospective Observational Study. Anesthesiology. 2019 Jul;131(1):74-83. doi: 10.1097/ALN.0000000000002703.</citation>
      <PMID>30998509</PMID>
    </results_reference>
    <results_reference>
      <citation>Ard JL, Kendale S. Searching for baseline blood pressure: A comparison of blood pressure at three different care points. J Clin Neurosci. 2016 Dec;34:59-62. doi: 10.1016/j.jocn.2016.08.001. Epub 2016 Aug 17.</citation>
      <PMID>27544232</PMID>
    </results_reference>
    <results_reference>
      <citation>Mathis MR, Naik BI, Freundlich RE, Shanks AM, Heung M, Kim M, Burns ML, Colquhoun DA, Rangrass G, Janda A, Engoren MC, Saager L, Tremper KK, Kheterpal S, Aziz MF, Coffman T, Durieux ME, Levy WJ, Schonberger RB, Soto R, Wilczak J, Berman MF, Berris J, Biggs DA, Coles P, Craft RM, Cummings KC, Ellis TA 2nd, Fleishut PM, Helsten DL, Jameson LC, van Klei WA, Kooij F, LaGorio J, Lins S, Miller SA, Molina S, Nair B, Paganelli WC, Peterson W, Tom S, Wanderer JP, Wedeven C; Multicenter Perioperative Outcomes Group Investigators. Preoperative Risk and the Association between Hypotension and Postoperative Acute Kidney Injury. Anesthesiology. 2020 Mar;132(3):461-475. doi: 10.1097/ALN.0000000000003063. Erratum In: Anesthesiology. 2020 Jan 6;:</citation>
      <PMID>31794513</PMID>
    </results_reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>September 4, 2023</last_update_submitted>
    <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Tongji Hospital</investigator_affiliation>
      <investigator_full_name>Ailin Luo</investigator_full_name>
      <investigator_title>Professor and Chief Physician</investigator_title>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Propofol</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>This is a multicenter clinical study and the plan need depend on multiple hospital views.</ipd_description>
    </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/NCT06009991
  org study id: TongjiHospital-Anes QQ02
  nct id: NCT06009991
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This is a multicenter, randomized, parallel, controlled clinical study of patients at
        different ages underwent elective non-cardiac surgery under general anesthesia. The aim of
        this study is to explore the dose range of remimazolam besylate for patients at different
        ages, to provide guidance for anesthesia induction and maintenance of remimazolam besylate.
        And to investigate the incidence of perioperative hypotension and postoperative related organ
        dysfunction in patients received total intravenous anesthesia with remimazolam besylate,
        compared with propofol.
  Surgery is an effective method to treat surgical diseases, prolong survival time and improve
        the quality of life, but patients often face the risk of postoperative complications. In
        general surgery patients, complications occur in more than 30% of patients. Several
        observational studies have shown that the severity and duration of intraoperative hypotension
        are significantly related to the risk of postoperative adverse events such as myocardial
        injury, renal injury, stroke, delirium, prolonged hospitalization, and death.
  
        Hypotension, defined as a systolic blood pressure of less than 90 mmHg, a diastolic blood
        pressure of less than 50 mmHg, or a 20% reduction in systolic blood pressure from baseline,
        is common during anesthesia and surgery. More than a third of patients receiving propofol
        sedation experience intraoperative hypotension events, and their duration and degree are
        associated with harm during surgery.
  
        Remimazolam is a new ultra-short-acting sedative drug developed in recent years, which has a
        similar structure to midazolam. However, compared with midazolam, remimazolam has the
        advantages of faster onset, faster recovery, and higher safety. Compared with propofol,
        remimazolam is noninferior in the success rate of sedation, while the incidence of adverse
        events such as hypotension is lower. At present, remimazolam has completed phase III clinical
        studies in many fields, such as colonoscopy, fiberoptic bronchoscopy, and general anesthesia
        induction and maintenance, which have shown its safety and effectiveness. However, there may
        be differences in hemodynamics and drug sensitivity among patients of different ages.
        Compared with young patients, elderly patients have a higher risk of hypotension after
        anesthesia induction. At present, there is a lack of clinical studies with large samples to
        clarify the recommended dose of remimazolam for anesthesia induction and maintenance in
        patients of all ages. The updated instructions for remimazolam besylate for injection on
        March 28, 2022 also mention that remimazolam besylate is used as a sedative drug for general
        anesthesia induction and maintenance, and the relevant dose reference is given. However, the
        safety and effectiveness of patients over 65 years have not been confirmed. The precise
        regulation of clinical use for patients of different ages and the optimization of drug dosage
        during anesthesia induction and maintenance are the basis for ensuring the safety of clinical
        medication at present., in order to maintain the stability of perioperative hemodynamics, and
        prevent or reduce the occurrence of adverse cardiovascular events.
  
        This study aims to investigate the effect of remimazolam total intravenous anesthesia on
        intraoperative hemodynamics and the drug requirement for patients of different ages, with
        propofol as the control, and intraoperative hemodynamics as the main evaluation index, so as
        to provide evidence for clinical application of remimazolam for elderly patients in
        anesthesia induction and maintenance.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Single (Participant)
  measure: Occurrence of intraoperative hypotension
  time frame: Operation 1 day
  description: Occurrence of intraoperative hypotension
  measure: Intraoperative dosage of vasoactive drugs
  time frame: Operation 1 day
  description: Intraoperative dosage of vasoactive drugs
  measure: Anesthesia recovery
  time frame: Operation 1 day
  description: Anesthesia recovery
  measure: Cognitive function assessment
  time frame: Operation 1 day
  description: Cognitive function assessment in the anesthesia recovery room
  measure: Major organ complications
  time frame: Within 30 days after surgery
  description: The occurrence of major organ complications within 30 days after surgery
  measure: Hospital stay of patients
  time frame: With 30 days after surgery
  description: Hospital stay of patients
  measure: 30-day mortality after surgery
  time frame: 30-day after surgery
  description: 30-day mortality after surgery
  arm group label: Age 45-64
  arm group type: Experimental
  description: Patients aged 45 to 64 years
  arm group label: Age 65-74
  arm group type: Experimental
  description: Patients aged 65 to 74 years
  arm group label: Age 75-84
  arm group type: Experimental
  description: Patients aged 75 to 84 years
  arm group label: Age over 75
  arm group type: Experimental
  description: Patients aged over 85 years
  intervention type: Drug
  intervention name: Remimazolam besylate
  description: Age 45-64: Remimazolam Besylate 0.3 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need).
  Age over 65: Remimazolam Besylate 0.15 mg/kg for anesthesia induction (0.05mg/kg for additional need) and 0.5mg/kg/h for maintenance (0.25 mg/kg/h for additional need).
  arm group label: Age 45-64
  arm group label: Age 65-74
  arm group label: Age 75-84
  arm group label: Age over 75
  intervention type: Drug
  intervention name: Propofol
  description: Age 45-64: Propofol 3.0μg/ml TCI for anesthesia induction and 2.5-3.0μg/ml TCI for maintenance.
  Age over 65: Propofol 1.5-2.5μg/ml TCI for anesthesia induction and 1.5-2.5μg/ml TCI for maintenance
  arm group label: Age 45-64
  arm group label: Age 65-74
  arm group label: Age 75-84
  arm group label: Age over 75
  criteria: 
  gender: All
  minimum age: 45 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Ailin Luo
  role: Principal Investigator
  affiliation: Tongji Hospital
  last name: Qiaoqiao Xu
  phone: +8618771006963
  email: qiaoqiaoxu@aliyun.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  citation: Ghaferi AA, Birkmeyer JD, Dimick JB. Complications, failure to rescue, and mortality with major inpatient surgery in medicare patients. Ann Surg. 2009 Dec;250(6):1029-34. doi: 10.1097/sla.0b013e3181bef697.
  PMID: 19953723
  citation: Wesselink EM, Kappen TH, Torn HM, Slooter AJC, van Klei WA. Intraoperative hypotension and the risk of postoperative adverse outcomes: a systematic review. Br J Anaesth. 2018 Oct;121(4):706-721. doi: 10.1016/j.bja.2018.04.036. Epub 2018 Jun 20.
  PMID: 30236233
  citation: Mascha EJ, Yang D, Weiss S, Sessler DI. Intraoperative Mean Arterial Pressure Variability and 30-day Mortality in Patients Having Noncardiac Surgery. Anesthesiology. 2015 Jul;123(1):79-91. doi: 10.1097/ALN.0000000000000686.
  PMID: 25929547
  citation: Salmasi V, Maheshwari K, Yang D, Mascha EJ, Singh A, Sessler DI, Kurz A. Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A Retrospective Cohort Analysis. Anesthesiology. 2017 Jan;126(1):47-65. doi: 10.1097/ALN.0000000000001432.
  PMID: 27792044
  citation: Babazade R, Yilmaz HO, Zimmerman NM, Stocchi L, Gorgun E, Kessler H, Sessler DI, Kurz A, Turan A. Association Between Intraoperative Low Blood Pressure and Development of Surgical Site Infection After Colorectal Surgery: A Retrospective Cohort Study. Ann Surg. 2016 Dec;264(6):1058-1064. doi: 10.1097/SLA.0000000000001607.
  PMID: 26756765
  citation: Futier E, Lefrant JY, Guinot PG, Godet T, Lorne E, Cuvillon P, Bertran S, Leone M, Pastene B, Piriou V, Molliex S, Albanese J, Julia JM, Tavernier B, Imhoff E, Bazin JE, Constantin JM, Pereira B, Jaber S; INPRESS Study Group. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial. JAMA. 2017 Oct 10;318(14):1346-1357. doi: 10.1001/jama.2017.14172.
  PMID: 28973220
  citation: Hallqvist L, Granath F, Fored M, Bell M. Intraoperative Hypotension and Myocardial Infarction Development Among High-Risk Patients Undergoing Noncardiac Surgery: A Nested Case-Control Study. Anesth Analg. 2021 Jul 1;133(1):6-15. doi: 10.1213/ANE.0000000000005391.
  PMID: 33555690
  citation: Ahuja S, Mascha EJ, Yang D, Maheshwari K, Cohen B, Khanna AK, Ruetzler K, Turan A, Sessler DI. Associations of Intraoperative Radial Arterial Systolic, Diastolic, Mean, and Pulse Pressures with Myocardial and Acute Kidney Injury after Noncardiac Surgery: A Retrospective Cohort Analysis. Anesthesiology. 2020 Feb;132(2):291-306. doi: 10.1097/ALN.0000000000003048.
  PMID: 31939844
  citation: Sneyd JR, Absalom AR, Barends CRM, Jones JB. Hypotension during propofol sedation for colonoscopy: a retrospective exploratory analysis and meta-analysis. Br J Anaesth. 2022 Apr;128(4):610-622. doi: 10.1016/j.bja.2021.10.044. Epub 2021 Dec 13.
  PMID: 34916051
  citation: Chen SH, Yuan TM, Zhang J, Bai H, Tian M, Pan CX, Bao HG, Jin XJ, Ji FH, Zhong TD, Wang Q, Lv JR, Wang S, Li YJ, Yu YH, Luo AL, Li XK, Min S, Li L, Zou XH, Huang YG. Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non-inferiority, phase III trial. J Gastroenterol Hepatol. 2021 Feb;36(2):474-481. doi: 10.1111/jgh.15188. Epub 2020 Jul 24.
  PMID: 32677707
  citation: Rex DK, Bhandari R, Desta T, DeMicco MP, Schaeffer C, Etzkorn K, Barish CF, Pruitt R, Cash BD, Quirk D, Tiongco F, Sullivan S, Bernstein D. A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy. Gastrointest Endosc. 2018 Sep;88(3):427-437.e6. doi: 10.1016/j.gie.2018.04.2351. Epub 2018 Apr 30.
  PMID: 29723512
  citation: Pastis NJ, Yarmus LB, Schippers F, Ostroff R, Chen A, Akulian J, Wahidi M, Shojaee S, Tanner NT, Callahan SP, Feldman G, Lorch DG Jr, Ndukwu I, Pritchett MA, Silvestri GA; PAION Investigators. Safety and Efficacy of Remimazolam Compared With Placebo and Midazolam for Moderate Sedation During Bronchoscopy. Chest. 2019 Jan;155(1):137-146. doi: 10.1016/j.chest.2018.09.015. Epub 2018 Oct 4.
  PMID: 30292760
  citation: Doi M, Morita K, Takeda J, Sakamoto A, Yamakage M, Suzuki T. Efficacy and safety of remimazolam versus propofol for general anesthesia: a multicenter, single-blind, randomized, parallel-group, phase IIb/III trial. J Anesth. 2020 Aug;34(4):543-553. doi: 10.1007/s00540-020-02788-6. Epub 2020 May 16.
  PMID: 32417976
  citation: Doi M, Hirata N, Suzuki T, Morisaki H, Morimatsu H, Sakamoto A. Safety and efficacy of remimazolam in induction and maintenance of general anesthesia in high-risk surgical patients (ASA Class III): results of a multicenter, randomized, double-blind, parallel-group comparative trial. J Anesth. 2020 Aug;34(4):491-501. doi: 10.1007/s00540-020-02776-w. Epub 2020 Apr 17.
  PMID: 32303884
  citation: Chen B, Pang QY, An R, Liu HL. A systematic review of risk factors for postinduction hypotension in surgical patients undergoing general anesthesia. Eur Rev Med Pharmacol Sci. 2021 Nov;25(22):7044-7050. doi: 10.26355/eurrev_202111_27255.
  PMID: 34859868
  citation: Saugel B, Reese PC, Sessler DI, Burfeindt C, Nicklas JY, Pinnschmidt HO, Reuter DA, Sudfeld S. Automated Ambulatory Blood Pressure Measurements and Intraoperative Hypotension in Patients Having Noncardiac Surgery with General Anesthesia: A Prospective Observational Study. Anesthesiology. 2019 Jul;131(1):74-83. doi: 10.1097/ALN.0000000000002703.
  PMID: 30998509
  citation: Ard JL, Kendale S. Searching for baseline blood pressure: A comparison of blood pressure at three different care points. J Clin Neurosci. 2016 Dec;34:59-62. doi: 10.1016/j.jocn.2016.08.001. Epub 2016 Aug 17.
  PMID: 27544232
  citation: Mathis MR, Naik BI, Freundlich RE, Shanks AM, Heung M, Kim M, Burns ML, Colquhoun DA, Rangrass G, Janda A, Engoren MC, Saager L, Tremper KK, Kheterpal S, Aziz MF, Coffman T, Durieux ME, Levy WJ, Schonberger RB, Soto R, Wilczak J, Berman MF, Berris J, Biggs DA, Coles P, Craft RM, Cummings KC, Ellis TA 2nd, Fleishut PM, Helsten DL, Jameson LC, van Klei WA, Kooij F, LaGorio J, Lins S, Miller SA, Molina S, Nair B, Paganelli WC, Peterson W, Tom S, Wanderer JP, Wedeven C; Multicenter Perioperative Outcomes Group Investigators. Preoperative Risk and the Association between Hypotension and Postoperative Acute Kidney Injury. Anesthesiology. 2020 Mar;132(3):461-475. doi: 10.1097/ALN.0000000000003063. Erratum In: Anesthesiology. 2020 Jan 6;:
  PMID: 31794513
  responsible party type: Principal Investigator
  investigator affiliation: Tongji Hospital
  investigator full name: Ailin Luo
  investigator title: Professor and Chief Physician
  mesh term: Propofol
  sharing ipd: No
  ipd description: This is a multicenter clinical study and the plan need depend on multiple hospital views.