<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/NCT03795259</url>
  </required_header>
  <id_info>
    <org_study_id>83045809-604.01</org_study_id>
    <nct_id>NCT03795259</nct_id>
  </id_info>
  <brief_title>Effect of Rocuronium and Sugammadex Under Sevoflurane and Desflurane Anesthesia in Children</brief_title>
  <official_title>Effect of Rocuronium and Sugammadex Under Sevoflurane and Desflurane Anesthesia in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istanbul University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GAMZE PİRİNÇ ŞAŞIOĞLU</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>GÜNER KAYA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ayse Cigdem Tutuncu</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Istanbul University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Sugammadex is the first selective relaxant binding agent approved to reverse certain&#xD;
      non-depolarizing neuromuscular drugs in patients 2 years old and above. Although it has been&#xD;
      in use over the last 10 years, more pharmacological studies are needed to understand its&#xD;
      overall effects on participants.&#xD;
&#xD;
      As investigators' primary outcome, the investigators aimed to investigate how differently&#xD;
      sugammadex reverses neumuscular blockade caused by rocuronium under general anesthesia&#xD;
      maintenance with sevoflurane compared with desflurane. Also, to compare the changes in peak&#xD;
      airway pressure. As investigators' secondary outcome, the investigators aimed to compare the&#xD;
      changes in heart rate and blood pressures after sugammadex injection under sevoflurane and&#xD;
      desflurane general anesthesia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      160 participants aged between 2-10 years old and scheduled for lower urinary tract or minor&#xD;
      abdominal surgery will be enrolled in the study. Each participant will be assigned&#xD;
      sevoflurane (Group S) or desflurane (Group D) anesthesia at enrollment by drawing lots.&#xD;
      Parental consent after written and verbal information will be asked on the morning of the&#xD;
      surgery.&#xD;
&#xD;
      Participants will be premedicated with midazolam (0.05 mg/kg, Zolamid, Defarma-Turkey) and&#xD;
      ketamine (0.1 mg/kg, Ketalar, Pfizer-USA) and brought into operating theater. Routine&#xD;
      monitoring will be done with non-invasive blood pressure (every 5 minutes), continuous&#xD;
      peripheral oxygen saturation, continuous 3-lead ECG, body temperature and continuous&#xD;
      end-tidal carbon dioxide measurements. Participants will be actively warmed to ensure&#xD;
      normo-thermia. Train-of-four (TOF) measurements will be performed on the arm without the&#xD;
      vascular access.&#xD;
&#xD;
      Anesthesia will be induced with thiopenthal (5-6 mg/kg, Pental, Ulagay-Turkey) and fentanyl&#xD;
      (2 mcg/kg, Talinat, VEM-Turkey). After the participant loses consciousness, TOF calibration&#xD;
      will be performed and baseline value will be recorded. Then 0.6 mg/kg rocuronium (Myocron,&#xD;
      VEM-Turkey) will be given intravenously and serial TOF measurements at 15 seconds intervals&#xD;
      will be taken. The time from TOF of 100% to 0% will be recorded as T1. Participant will be&#xD;
      orotracheal intubated when the TOF value is 0%. All the patients will be ventilated with&#xD;
      Datex Ohmeda S/5 Avance in a volume controlled ventilation mode (air-oxygen mixture, FiO2:&#xD;
      40%, I/E: 1/1.5, PEEP: 5 cmH2O, tidal volume: 8ml/kg). Participant will receive 2%&#xD;
      sevoflurane (Sevoran, Abbvie-Italy) or 6% desflurane (Suprane, Baxter-Belgium) according to&#xD;
      their groups.&#xD;
&#xD;
      Non-invasive blood pressure, heart rate and peak airway pressure will be recorded at 5 minute&#xD;
      intervals after orotracheal intubation. Continuous TOF measurements will be taken until TOF&#xD;
      value reaches 25%. Time from TOF of 0% to 25% will be recorded as T2.&#xD;
&#xD;
      When the TOF value is 25%, 2 mg/kg sugammadex (Bridion, MSD-Greece) will be given&#xD;
      intravenously and TOF measurements will continue every 15 seconds. The time from sugammadex&#xD;
      injection (TOF of 25%) to TOF of 90% will be recorded as T3. Non-invasive blood pressure,&#xD;
      heart rate and peak airway pressure will be recorded at the time of sugammadex injection and&#xD;
      at 1st, 2nd, 3rd and 10th minutes. Any reactions to sugammadex will be recorded (anaphylaxis,&#xD;
      bronchospasm, etc.).&#xD;
&#xD;
      T1, T2 and T3 of Group S and D will be compared. Non-invasive blood pressure, heart rate and&#xD;
      peak airway pressure after sugammadex injection at time 0min, 1min, 2min, 3min and 10min will&#xD;
      be compared.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 28, 2018</start_date>
  <completion_date type="Actual">May 19, 2019</completion_date>
  <primary_completion_date type="Actual">May 19, 2019</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>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time from TOF of 25% to 90% after 2 mg/kg sugammadex injection</measure>
    <time_frame>Up to end of surgery</time_frame>
    <description>When the TOF value reaches 25% from 0% after the anesthesia induction, 2 mg/kg sugammadex will be given to reverse neuromuscular blockade. Continuous TOF monitoring will continue every 15 seconds. The time it takes for TOF to reach 90% is the primary outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time from TOF of 100% to 0% after 0.6 mg/kg rocuronium injection</measure>
    <time_frame>Up to end of surgery</time_frame>
    <description>After induction of anesthesia a baseline TOF will be recorded (anticipated 100%). 0.6 mg/kg rocuronium will be injected and TOF will be measured every 15 seconds. The time it takes for TOF to reach 0% is the second primary outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time from TOF of 0% to 25% after orotracheal intubation</measure>
    <time_frame>Up to end of surgery</time_frame>
    <description>After TOF reaches 0%, orotracheal intubation will be performed. Continuous TOF monitoring will be done every 5 minutes in first 15 minutes and every 15 seconds afterwards. No additional neuromuscular blocking drugs will be given. The time it takes for TOF to reach 25% is the third primary outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sugammadex effects on respiratory parameters</measure>
    <time_frame>Up to 10 minutes post-administration of study intervention</time_frame>
    <description>Peak airway pressure observed at and after sugammadex injection at 1st, 2nd, 3rd and 10th minutes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sugammadex effects on heart rate</measure>
    <time_frame>Up to 10 minutes post-administration of study intervention</time_frame>
    <description>Heart rate observed at and after sugammadex injection at 1st, 2nd, 3rd and 10th minutes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sugammadex effects on systolic and diastolic blood pressures</measure>
    <time_frame>Up to 10 minutes post-administration of study intervention</time_frame>
    <description>blood pressures observed at and after sugammadex injection at 1st, 2nd, 3rd and 10th minutes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Experiencing an Adverse Event (AE) after Administration of Study Intervention</measure>
    <time_frame>Intraoperative and postoperative first 24 hour.</time_frame>
    <description>Observation bronchospasm and anaphylaxis after sugammadex injection</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">148</enrollment>
  <condition>Anesthetics, Inhalation</condition>
  <condition>Neuromuscular Blockade</condition>
  <condition>Anesthesia, General</condition>
  <arm_group>
    <arm_group_label>Sevoflurane</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Anesthesia will be induced with thiopenthal 5-6 mg/kg and fentanyl 2 mcg/kg. Then rocuronium 0.6 mg/kg will be given by intravenously and patients will be orotracheal intubated when TOF value reaches 0%. Anesthesia will continue with 2% sevoflurane while the patient is ventilated in volume controlled mode (FiO2: 40%, I/E: 1/1.5, PEEP: 5 cmH2O, tidal volume: 8ml/kg). Continuous TOF measurement will continue until the value reaches %25. At this time, sugammadex 2 mg/kg will be given to measure the time for TOF to reach 90%.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Desflurane</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Anesthesia will be induced with thiopenthal 5-6 mg/kg and fentanyl 2 mcg/kg. Then rocuronium 0.6 mg/kg will be given by intravenously and patients will be orotracheal intubated when TOF value reaches 0%. Anesthesia will continue with 6% desflurane while the patient is ventilated in volume controlled mode (FiO2: 40%, I/E: 1/1.5, PEEP: 5 cmH2O, tidal volume: 8ml/kg). Continuous TOF measurement will continue until the value reaches %25. At this time, sugammadex 2 mg/kg will be given to measure the time for TOF to reach 90%.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rocuronium</intervention_name>
    <description>After induction, rocuronium 0.6 mg/kg will be given by intravenously and patients will be orotracheal intubated when TOF value reaches 0%.</description>
    <arm_group_label>Desflurane</arm_group_label>
    <arm_group_label>Sevoflurane</arm_group_label>
    <other_name>Esmeron, MSD</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sugammadex</intervention_name>
    <description>Continuous TOF measurement will continue until the value reaches %25. At this time, sugammadex 2 mg/kg will be given intravenously.</description>
    <arm_group_label>Desflurane</arm_group_label>
    <arm_group_label>Sevoflurane</arm_group_label>
    <other_name>Bridion, MSD</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Lower urinary tract surgery (cystoscopy, examination under general anaesthesia,&#xD;
             circumcision etc.) and inguinal hernia surgery expected no to last more than 2 hours&#xD;
&#xD;
          -  ASA I-II&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Liver and failure&#xD;
&#xD;
          -  Upper airway infection&#xD;
&#xD;
          -  Asthma&#xD;
&#xD;
          -  Exposure to second hand smoke&#xD;
&#xD;
          -  Kidney failure&#xD;
&#xD;
          -  Obesity (BMI&gt; 30%)&#xD;
&#xD;
          -  Rocuronium allergy&#xD;
&#xD;
          -  Muscle disease (myasthenia gravis, muscular dystrophies, etc.)&#xD;
&#xD;
          -  Calcium channel blocker use&#xD;
&#xD;
          -  Patient or family refusal&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>10 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Guner Kaya, Prof.</last_name>
    <role>Study Director</role>
    <affiliation>Istanbul University Cerrahpasa Medical Faculty</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Istanbul University Cerrahpasa Medical Faculty</name>
      <address>
        <city>Istanbul</city>
        <state>Please Select</state>
        <zip>34098</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>December 27, 2018</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>April 29, 2021</last_update_submitted>
  <last_update_submitted_qc>April 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Istanbul University</investigator_affiliation>
    <investigator_full_name>pinar kendigelen</investigator_full_name>
    <investigator_title>MD, Principal investigator</investigator_title>
  </responsible_party>
  <keyword>Sugammadex</keyword>
  <keyword>Sevoflurane</keyword>
  <keyword>Desflurane</keyword>
  <keyword>Rocuronium</keyword>
  <keyword>TOF</keyword>
  <keyword>Child</keyword>
  <keyword>Train-of-four</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Aspiration</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rocuronium</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03795259
org study id: 83045809-604.01
nct id: NCT03795259
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Sugammadex is the first selective relaxant binding agent approved to reverse certain
      non-depolarizing neuromuscular drugs in patients 2 years old and above. Although it has been
      in use over the last 10 years, more pharmacological studies are needed to understand its
      overall effects on participants.

      As investigators' primary outcome, the investigators aimed to investigate how differently
      sugammadex reverses neumuscular blockade caused by rocuronium under general anesthesia
      maintenance with sevoflurane compared with desflurane. Also, to compare the changes in peak
      airway pressure. As investigators' secondary outcome, the investigators aimed to compare the
      changes in heart rate and blood pressures after sugammadex injection under sevoflurane and
      desflurane general anesthesia.
160 participants aged between 2-10 years old and scheduled for lower urinary tract or minor
      abdominal surgery will be enrolled in the study. Each participant will be assigned
      sevoflurane (Group S) or desflurane (Group D) anesthesia at enrollment by drawing lots.
      Parental consent after written and verbal information will be asked on the morning of the
      surgery.

      Participants will be premedicated with midazolam (0.05 mg/kg, Zolamid, Defarma-Turkey) and
      ketamine (0.1 mg/kg, Ketalar, Pfizer-USA) and brought into operating theater. Routine
      monitoring will be done with non-invasive blood pressure (every 5 minutes), continuous
      peripheral oxygen saturation, continuous 3-lead ECG, body temperature and continuous
      end-tidal carbon dioxide measurements. Participants will be actively warmed to ensure
      normo-thermia. Train-of-four (TOF) measurements will be performed on the arm without the
      vascular access.

      Anesthesia will be induced with thiopenthal (5-6 mg/kg, Pental, Ulagay-Turkey) and fentanyl
      (2 mcg/kg, Talinat, VEM-Turkey). After the participant loses consciousness, TOF calibration
      will be performed and baseline value will be recorded. Then 0.6 mg/kg rocuronium (Myocron,
      VEM-Turkey) will be given intravenously and serial TOF measurements at 15 seconds intervals
      will be taken. The time from TOF of 100% to 0% will be recorded as T1. Participant will be
      orotracheal intubated when the TOF value is 0%. All the patients will be ventilated with
      Datex Ohmeda S/5 Avance in a volume controlled ventilation mode (air-oxygen mixture, FiO2:
      40%, I/E: 1/1.5, PEEP: 5 cmH2O, tidal volume: 8ml/kg). Participant will receive 2%
      sevoflurane (Sevoran, Abbvie-Italy) or 6% desflurane (Suprane, Baxter-Belgium) according to
      their groups.

      Non-invasive blood pressure, heart rate and peak airway pressure will be recorded at 5 minute
      intervals after orotracheal intubation. Continuous TOF measurements will be taken until TOF
      value reaches 25%. Time from TOF of 0% to 25% will be recorded as T2.

      When the TOF value is 25%, 2 mg/kg sugammadex (Bridion, MSD-Greece) will be given
      intravenously and TOF measurements will continue every 15 seconds. The time from sugammadex
      injection (TOF of 25%) to TOF of 90% will be recorded as T3. Non-invasive blood pressure,
      heart rate and peak airway pressure will be recorded at the time of sugammadex injection and
      at 1st, 2nd, 3rd and 10th minutes. Any reactions to sugammadex will be recorded (anaphylaxis,
      bronchospasm, etc.).

      T1, T2 and T3 of Group S and D will be compared. Non-invasive blood pressure, heart rate and
      peak airway pressure after sugammadex injection at time 0min, 1min, 2min, 3min and 10min will
      be compared.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Screening
masking: None (Open Label)
measure: Time from TOF of 25% to 90% after 2 mg/kg sugammadex injection
time frame: Up to end of surgery
description: When the TOF value reaches 25% from 0% after the anesthesia induction, 2 mg/kg sugammadex will be given to reverse neuromuscular blockade. Continuous TOF monitoring will continue every 15 seconds. The time it takes for TOF to reach 90% is the primary outcome.
measure: Time from TOF of 100% to 0% after 0.6 mg/kg rocuronium injection
time frame: Up to end of surgery
description: After induction of anesthesia a baseline TOF will be recorded (anticipated 100%). 0.6 mg/kg rocuronium will be injected and TOF will be measured every 15 seconds. The time it takes for TOF to reach 0% is the second primary outcome.
measure: Time from TOF of 0% to 25% after orotracheal intubation
time frame: Up to end of surgery
description: After TOF reaches 0%, orotracheal intubation will be performed. Continuous TOF monitoring will be done every 5 minutes in first 15 minutes and every 15 seconds afterwards. No additional neuromuscular blocking drugs will be given. The time it takes for TOF to reach 25% is the third primary outcome.
measure: Sugammadex effects on respiratory parameters
time frame: Up to 10 minutes post-administration of study intervention
description: Peak airway pressure observed at and after sugammadex injection at 1st, 2nd, 3rd and 10th minutes.
measure: Sugammadex effects on heart rate
time frame: Up to 10 minutes post-administration of study intervention
description: Heart rate observed at and after sugammadex injection at 1st, 2nd, 3rd and 10th minutes.
measure: Sugammadex effects on systolic and diastolic blood pressures
time frame: Up to 10 minutes post-administration of study intervention
description: blood pressures observed at and after sugammadex injection at 1st, 2nd, 3rd and 10th minutes.
measure: Percentage of Participants Experiencing an Adverse Event (AE) after Administration of Study Intervention
time frame: Intraoperative and postoperative first 24 hour.
description: Observation bronchospasm and anaphylaxis after sugammadex injection
arm group label: Sevoflurane
arm group type: Active Comparator
description: Anesthesia will be induced with thiopenthal 5-6 mg/kg and fentanyl 2 mcg/kg. Then rocuronium 0.6 mg/kg will be given by intravenously and patients will be orotracheal intubated when TOF value reaches 0%. Anesthesia will continue with 2% sevoflurane while the patient is ventilated in volume controlled mode (FiO2: 40%, I/E: 1/1.5, PEEP: 5 cmH2O, tidal volume: 8ml/kg). Continuous TOF measurement will continue until the value reaches %25. At this time, sugammadex 2 mg/kg will be given to measure the time for TOF to reach 90%.
arm group label: Desflurane
arm group type: Active Comparator
description: Anesthesia will be induced with thiopenthal 5-6 mg/kg and fentanyl 2 mcg/kg. Then rocuronium 0.6 mg/kg will be given by intravenously and patients will be orotracheal intubated when TOF value reaches 0%. Anesthesia will continue with 6% desflurane while the patient is ventilated in volume controlled mode (FiO2: 40%, I/E: 1/1.5, PEEP: 5 cmH2O, tidal volume: 8ml/kg). Continuous TOF measurement will continue until the value reaches %25. At this time, sugammadex 2 mg/kg will be given to measure the time for TOF to reach 90%.
intervention type: Drug
intervention name: Rocuronium
description: After induction, rocuronium 0.6 mg/kg will be given by intravenously and patients will be orotracheal intubated when TOF value reaches 0%.
arm group label: Desflurane
arm group label: Sevoflurane
other name: Esmeron, MSD
intervention type: Drug
intervention name: Sugammadex
description: Continuous TOF measurement will continue until the value reaches %25. At this time, sugammadex 2 mg/kg will be given intravenously.
arm group label: Desflurane
arm group label: Sevoflurane
other name: Bridion, MSD
criteria: 
gender: All
minimum age: 2 Years
maximum age: 10 Years
healthy volunteers: No
last name: Guner Kaya, Prof.
role: Study Director
affiliation: Istanbul University Cerrahpasa Medical Faculty
facility: 
country: Turkey
responsible party type: Principal Investigator
investigator affiliation: Istanbul University
investigator full name: pinar kendigelen
investigator title: MD, Principal investigator
mesh term: Respiratory Aspiration
mesh term: Rocuronium
sharing ipd: Undecided