<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/NCT04507165</url>
  </required_header>
  <id_info>
    <org_study_id>2020PHB031</org_study_id>
    <nct_id>NCT04507165</nct_id>
  </id_info>
  <brief_title>Opioid-free Anesthesia in VATS Lung Resection</brief_title>
  <official_title>The Effect of Opioid-free Anesthesia on Postoperative Analgesia-related Adverse Reactions in Lung Resection With Video-assisted Thoracoscopic Access: a Randomized Double-blind Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University People's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking University People's Hospital</source>
  <oversight_info>
    <has_dmc>No</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>
      A comparison of incidences of postoperative opioid-related adverse effects and recovery&#xD;
      parameters in patients undergoing video-assisted thoracoscopic surgery (VATS) lung resection&#xD;
      receiving opioid or opioid-free general anesthesia (OFA).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Video-assisted thoracoscopic surgery (VATS) lung resection is traditionally performed under&#xD;
      general anesthesia with opioid-based analgesia. It is associated with higher incidences of&#xD;
      respiratory depression, hypotension, postoperative nausea and vomiting (PONV), dizziness,&#xD;
      constipation and urinary retention, and more severe acute postoperative pain.&#xD;
&#xD;
      The purpose of our study is to compare the opioid-free general anesthesia with the&#xD;
      opioid-based general anesthesia with respect to the primary outcome measures of the total&#xD;
      incidence of opioid-related adverse effects (including respiratory depression, hypotension,&#xD;
      PONV and dizziness) and secondary outcome measures of incidence of intraoperative and&#xD;
      postoperative cardiovascular complications, pain relief, analgesic requirement , and other&#xD;
      postoperative recovery parameters [e.g. duration of tracheal extubation, departing from&#xD;
      post-anaesthesia care unit (PACU), exhaust, defecation, and stay in hospital&#xD;
      postoperatively].&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 2020</start_date>
  <completion_date type="Anticipated">July 2022</completion_date>
  <primary_completion_date type="Anticipated">July 2021</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>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total incidence of opioid-related adverse effects of 2 hours, 4 hours, 6 hours, 24 hours and 48 hours postoperation</measure>
    <time_frame>2 hours, 4 hours, 6 hours, 24 hours and 48 hours postoperation</time_frame>
    <description>The total incidence refers to the sum of the incidence of opioid-related adverse effects at 2h, 4h, 6h, 24h and 48h postoperationOpioid-related adverse effects here including respiratory depression, hypotension, PONV and dizziness.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of intraoperative cardiovascular complications</measure>
    <time_frame>During the operation</time_frame>
    <description>Including the incidence of arrhythmia, the probability of using hyperensor and hypotensor.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of postoperative cardiovascular complications</measure>
    <time_frame>Up to 30 days postoperation</time_frame>
    <description>Including the incidence of arrhythmia, the probability of using hypertensor and hypotensor.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of tracheal intubation removing</measure>
    <time_frame>Up to 2 hours postoperation</time_frame>
    <description>From anesthetic discontinuance to tracheal extubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of departing from PACU</measure>
    <time_frame>Up to 4 hours postoperation</time_frame>
    <description>From tracheal extubation to Aldrete score&gt;9. Aldrete score is the standard for departing from PACU which includes five contents to evaluate: activity, breath, blood pressure, state of consciousness and oxygen saturation by pulse oximetry (SpO2). 2 point in total for each content. 2 point refers to the best state, whereas 0 point refers to the worst state. When a patient's total score greater than 9 who will be transferred out of PACU.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain severity</measure>
    <time_frame>2 hours, 4 hours, 6 hours, 24 hours and 48 hours after tracheal extubation</time_frame>
    <description>Using 0-10 numerical rating scale (NRS). The NRS score is ranged from 0 to 10. 0 means without pain. 1-3 means mild pain. 4-6 means moderate pain. 7-9 means severe pain. 10 means intense pain and can't bear.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dosage of opioids</measure>
    <time_frame>2 hours, 4 hours, 6 hours, 24 hours and 48 hours after tracheal extubation</time_frame>
    <description>Total dosage of opioids postoperation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Flatus time</measure>
    <time_frame>Up to 48 hours postoperation</time_frame>
    <description>From the operation finished to first-time exhaust</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Defecation time</measure>
    <time_frame>Up to 48 hours postoperation</time_frame>
    <description>From the operation finished to first-time defecation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative duration of stay in hospital</measure>
    <time_frame>30 days postoperation</time_frame>
    <description>The duration when patients stay in hospital after surgery.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Opioid Free Anesthesia</condition>
  <arm_group>
    <arm_group_label>opioid-free general anesthesia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>under opioid-free general anesthesia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>opioid based general anesthesia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>under opioid based general anesthesia</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Paravertebral block+Anterior serratus plane block</intervention_name>
    <description>Paravertebral block will be performed at T3 and T7 level on the surgical side using out-of-plane approach under ultrasound-guided, with 0.5% ropivacaine 10ml at each injection site. Anterior serratus plane block will be performed at the 4th rib level on the surgical side under ultrasound-guided, with 0.5% ropivacaine 15ml. The blocking range is measured by &quot;ice cube&quot; method 15 minutes after the procedure.</description>
    <arm_group_label>opioid based general anesthesia</arm_group_label>
    <arm_group_label>opioid-free general anesthesia</arm_group_label>
    <other_name>nerve block</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>opioid free anesthesia</intervention_name>
    <description>Anesthesia induction: Dexmedetomidine 1µg/kg (intravenous infusion within 10min), propofol 1.5-2mg/kg (intravenous bolus), lidocaine 1.5-2mg/kg (intravenous bolus), cisatracurium besylate 0.15-0.3mg/kg (intravenous bolus before tracheal intubation), methylprednisolone 40mg (intravenous bolus), esmolol 1mg/kg (intravenous bolus), and 0.5% tetracaine 5ml for surface anesthesia of the throat.&#xD;
Maintenance of anesthesia: Continuous infusion of propofol and dexmedetomidine [0.4μg/(kg.h)]. The infusion rate of propofol was adjusted according to bispectral index value. Cisatracurium besylate was given as needed. Flurbiprofen 50mg was given intravenously before the skin incision and suture respectively.&#xD;
Remedy: If blood pressure rises (more than 30% of the mean arterial pressure after induction), and heart rate increases (more than 30% of heart rate after induction) during skin incision, lidocaine 1.5mg/kg will be given intravenously and then be continuously infused at a rate of 1.5mg/(kg.h).</description>
    <arm_group_label>opioid-free general anesthesia</arm_group_label>
    <other_name>OFA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>opioid based anesthesia</intervention_name>
    <description>Anesthesia induction: Propofol 1.5-2mg/kg (intravenous bolus), sufentanil 0.3μg/kg (intravenous bolus), cisatracurium besylate 0.15-0.3mg/kg (intravenous bolus before tracheal intubation), methylprednisolone 40mg (intravenous bolus), esmolol 1mg/kg (intravenous bolus).&#xD;
Maintenance of anesthesia: Continuous infusion of propofol and remifentanil. The infusion rate of propofol was adjusted according to BIS value. The infusion rate of remifentanil was 0.1-0.5µg/(kg.min) and adjusted according to the change of heart rate and blood pressure. Cisatracurium besylate was given as needed. Sufentanil 0.1μg/kg and flurbiprofen 50mg were given intravenously before the skin incision and suture respectively.</description>
    <arm_group_label>opioid based general anesthesia</arm_group_label>
    <other_name>Standard anesthesia</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Undergoing VATS lung resection.&#xD;
&#xD;
          -  American Society of Anesthesiologists (ASA) physical status I-II.&#xD;
&#xD;
          -  Agreed to participate in the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  ASA phase III or above.&#xD;
&#xD;
          -  Undergoing emergency surgery.&#xD;
&#xD;
          -  Planning for thoracotomy.&#xD;
&#xD;
          -  Adults protected by law (under judicial protection, guardianship or supervision),&#xD;
             people who deprived of their liberty.&#xD;
&#xD;
          -  Patients who have received general anesthesia.&#xD;
&#xD;
          -  Atrioventricular block, sinus node block or intraventricular block.&#xD;
&#xD;
          -  Sinus bradycardia (heart rate is less than 60 beats/min).&#xD;
&#xD;
          -  Preoperative hypotension (systolic blood pressure is less than 90mmHg)&#xD;
&#xD;
          -  Combined with urolithiasis, Meniere syndrome, and vertebral artery stenosis&#xD;
&#xD;
          -  Combined with cerebrovascular disease.&#xD;
&#xD;
          -  Contraindication to NSAIDs drug.&#xD;
&#xD;
          -  Allergic to anesthetics.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Feng Yi, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University People's Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Feng Yi, MD,PhD</last_name>
    <phone>86-010-88325581</phone>
    <email>yifeng65@sina.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Peking University People's Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100044</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Dinges HC, Otto S, Stay DK, Baumlein S, Waldmann S, Kranke P, Wulf HF, Eberhart LH. Side Effect Rates of Opioids in Equianalgesic Doses via Intravenous Patient-Controlled Analgesia: A Systematic Review and Network Meta-analysis. Anesth Analg. 2019 Oct;129(4):1153-1162. doi: 10.1213/ANE.0000000000003887.</citation>
    <PMID>30418234</PMID>
  </reference>
  <reference>
    <citation>Cozowicz C, Poeran J, Zubizarreta N, Liu J, Weinstein SM, Pichler L, Mazumdar M, Memtsoudis SG. Non-opioid analgesic modes of pain management are associated with reduced postoperative complications and resource utilisation: a retrospective study of obstructive sleep apnoea patients undergoing elective joint arthroplasty. Br J Anaesth. 2019 Jan;122(1):131-140. doi: 10.1016/j.bja.2018.08.027. Epub 2018 Oct 27.</citation>
    <PMID>30579391</PMID>
  </reference>
  <reference>
    <citation>Forget P. Opioid-free anaesthesia. Why and how? A contextual analysis. Anaesth Crit Care Pain Med. 2019 Apr;38(2):169-172. doi: 10.1016/j.accpm.2018.05.002. Epub 2018 Sep 13.</citation>
    <PMID>29775728</PMID>
  </reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2020</study_first_posted>
  <last_update_submitted>August 6, 2020</last_update_submitted>
  <last_update_submitted_qc>August 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking University People's Hospital</investigator_affiliation>
    <investigator_full_name>Yi Feng, MD</investigator_full_name>
    <investigator_title>Chief of the Anesthesiology Department</investigator_title>
  </responsible_party>
  <keyword>Opioid Free Anesthesia</keyword>
  <keyword>Video-assisted Thoracoscopic Surgery</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Analgesics, Opioid</mesh_term>
    <mesh_term>Anesthetics</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04507165
org study id: 2020PHB031
nct id: NCT04507165
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A comparison of incidences of postoperative opioid-related adverse effects and recovery
      parameters in patients undergoing video-assisted thoracoscopic surgery (VATS) lung resection
      receiving opioid or opioid-free general anesthesia (OFA).
Video-assisted thoracoscopic surgery (VATS) lung resection is traditionally performed under
      general anesthesia with opioid-based analgesia. It is associated with higher incidences of
      respiratory depression, hypotension, postoperative nausea and vomiting (PONV), dizziness,
      constipation and urinary retention, and more severe acute postoperative pain.

      The purpose of our study is to compare the opioid-free general anesthesia with the
      opioid-based general anesthesia with respect to the primary outcome measures of the total
      incidence of opioid-related adverse effects (including respiratory depression, hypotension,
      PONV and dizziness) and secondary outcome measures of incidence of intraoperative and
      postoperative cardiovascular complications, pain relief, analgesic requirement , and other
      postoperative recovery parameters [e.g. duration of tracheal extubation, departing from
      post-anaesthesia care unit (PACU), exhaust, defecation, and stay in hospital
      postoperatively].
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Total incidence of opioid-related adverse effects of 2 hours, 4 hours, 6 hours, 24 hours and 48 hours postoperation
time frame: 2 hours, 4 hours, 6 hours, 24 hours and 48 hours postoperation
description: The total incidence refers to the sum of the incidence of opioid-related adverse effects at 2h, 4h, 6h, 24h and 48h postoperationOpioid-related adverse effects here including respiratory depression, hypotension, PONV and dizziness.
measure: Incidence of intraoperative cardiovascular complications
time frame: During the operation
description: Including the incidence of arrhythmia, the probability of using hyperensor and hypotensor.
measure: Incidence of postoperative cardiovascular complications
time frame: Up to 30 days postoperation
description: Including the incidence of arrhythmia, the probability of using hypertensor and hypotensor.
measure: Duration of tracheal intubation removing
time frame: Up to 2 hours postoperation
description: From anesthetic discontinuance to tracheal extubation
measure: Duration of departing from PACU
time frame: Up to 4 hours postoperation
description: From tracheal extubation to Aldrete score>9. Aldrete score is the standard for departing from PACU which includes five contents to evaluate: activity, breath, blood pressure, state of consciousness and oxygen saturation by pulse oximetry (SpO2). 2 point in total for each content. 2 point refers to the best state, whereas 0 point refers to the worst state. When a patient's total score greater than 9 who will be transferred out of PACU.
measure: Pain severity
time frame: 2 hours, 4 hours, 6 hours, 24 hours and 48 hours after tracheal extubation
description: Using 0-10 numerical rating scale (NRS). The NRS score is ranged from 0 to 10. 0 means without pain. 1-3 means mild pain. 4-6 means moderate pain. 7-9 means severe pain. 10 means intense pain and can't bear.
measure: Dosage of opioids
time frame: 2 hours, 4 hours, 6 hours, 24 hours and 48 hours after tracheal extubation
description: Total dosage of opioids postoperation
measure: Flatus time
time frame: Up to 48 hours postoperation
description: From the operation finished to first-time exhaust
measure: Defecation time
time frame: Up to 48 hours postoperation
description: From the operation finished to first-time defecation
measure: Postoperative duration of stay in hospital
time frame: 30 days postoperation
description: The duration when patients stay in hospital after surgery.
arm group label: opioid-free general anesthesia
arm group type: Experimental
description: under opioid-free general anesthesia
arm group label: opioid based general anesthesia
arm group type: Active Comparator
description: under opioid based general anesthesia
intervention type: Procedure
intervention name: Paravertebral block+Anterior serratus plane block
description: Paravertebral block will be performed at T3 and T7 level on the surgical side using out-of-plane approach under ultrasound-guided, with 0.5% ropivacaine 10ml at each injection site. Anterior serratus plane block will be performed at the 4th rib level on the surgical side under ultrasound-guided, with 0.5% ropivacaine 15ml. The blocking range is measured by "ice cube" method 15 minutes after the procedure.
arm group label: opioid based general anesthesia
arm group label: opioid-free general anesthesia
other name: nerve block
intervention type: Drug
intervention name: opioid free anesthesia
description: Anesthesia induction: Dexmedetomidine 1µg/kg (intravenous infusion within 10min), propofol 1.5-2mg/kg (intravenous bolus), lidocaine 1.5-2mg/kg (intravenous bolus), cisatracurium besylate 0.15-0.3mg/kg (intravenous bolus before tracheal intubation), methylprednisolone 40mg (intravenous bolus), esmolol 1mg/kg (intravenous bolus), and 0.5% tetracaine 5ml for surface anesthesia of the throat.
Maintenance of anesthesia: Continuous infusion of propofol and dexmedetomidine [0.4μg/(kg.h)]. The infusion rate of propofol was adjusted according to bispectral index value. Cisatracurium besylate was given as needed. Flurbiprofen 50mg was given intravenously before the skin incision and suture respectively.
Remedy: If blood pressure rises (more than 30% of the mean arterial pressure after induction), and heart rate increases (more than 30% of heart rate after induction) during skin incision, lidocaine 1.5mg/kg will be given intravenously and then be continuously infused at a rate of 1.5mg/(kg.h).
arm group label: opioid-free general anesthesia
other name: OFA
intervention type: Drug
intervention name: opioid based anesthesia
description: Anesthesia induction: Propofol 1.5-2mg/kg (intravenous bolus), sufentanil 0.3μg/kg (intravenous bolus), cisatracurium besylate 0.15-0.3mg/kg (intravenous bolus before tracheal intubation), methylprednisolone 40mg (intravenous bolus), esmolol 1mg/kg (intravenous bolus).
Maintenance of anesthesia: Continuous infusion of propofol and remifentanil. The infusion rate of propofol was adjusted according to BIS value. The infusion rate of remifentanil was 0.1-0.5µg/(kg.min) and adjusted according to the change of heart rate and blood pressure. Cisatracurium besylate was given as needed. Sufentanil 0.1μg/kg and flurbiprofen 50mg were given intravenously before the skin incision and suture respectively.
arm group label: opioid based general anesthesia
other name: Standard anesthesia
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Feng Yi, MD,PhD
role: Principal Investigator
affiliation: Peking University People's Hospital
last name: Feng Yi, MD,PhD
phone: 86-010-88325581
email: yifeng65@sina.com
facility: 
country: China
citation: Dinges HC, Otto S, Stay DK, Baumlein S, Waldmann S, Kranke P, Wulf HF, Eberhart LH. Side Effect Rates of Opioids in Equianalgesic Doses via Intravenous Patient-Controlled Analgesia: A Systematic Review and Network Meta-analysis. Anesth Analg. 2019 Oct;129(4):1153-1162. doi: 10.1213/ANE.0000000000003887.
PMID: 30418234
citation: Cozowicz C, Poeran J, Zubizarreta N, Liu J, Weinstein SM, Pichler L, Mazumdar M, Memtsoudis SG. Non-opioid analgesic modes of pain management are associated with reduced postoperative complications and resource utilisation: a retrospective study of obstructive sleep apnoea patients undergoing elective joint arthroplasty. Br J Anaesth. 2019 Jan;122(1):131-140. doi: 10.1016/j.bja.2018.08.027. Epub 2018 Oct 27.
PMID: 30579391
citation: Forget P. Opioid-free anaesthesia. Why and how? A contextual analysis. Anaesth Crit Care Pain Med. 2019 Apr;38(2):169-172. doi: 10.1016/j.accpm.2018.05.002. Epub 2018 Sep 13.
PMID: 29775728
responsible party type: Principal Investigator
investigator affiliation: Peking University People's Hospital
investigator full name: Yi Feng, MD
investigator title: Chief of the Anesthesiology Department
mesh term: Analgesics, Opioid
mesh term: Anesthetics
sharing ipd: No