<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/NCT03251170</url>
  </required_header>
  <id_info>
    <org_study_id>N-12-2018</org_study_id>
    <nct_id>NCT03251170</nct_id>
  </id_info>
  <brief_title>Ketamine Versus Fentanyl for Induction of Anesthesia in Septic Shock</brief_title>
  <official_title>Ketamine-based Versus Opioid-based for Rapid-sequence Induction of Anesthesia in Patients With Septic Shock</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cairo University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cairo 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>
      The aim of this work is to compare two protocols (ketamine-midazolam versus&#xD;
      fentanyl-midazolam) for induction of anesthesia in patients with septic shock aiming to find&#xD;
      the most safe protocol with regards to hemodynamic status of patients&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Induction of anesthesia in hemodynamically compromised patients is a challenge for every&#xD;
      anesthetist. Most of the intravenous induction agents have a negative effect on arterial&#xD;
      blood pressure and cardiac output. Theoretically, the &quot;ideal&quot; emergency induction intravenous&#xD;
      anesthetic should achieve rapid hypnosis and maintain the hemodynamic stability.&#xD;
&#xD;
      Ketamine has been reported as an induction anesthetic with a sympathomimetic activity. In&#xD;
      patients with intact autonomic nervous system ketamine increases heart rate, cardiac output,&#xD;
      and arterial blood pressure (ABP). Despite its sympathomimetic activity in hemodynamically&#xD;
      stable patients, the hemodynamic response to ketamine in unstable cardiovascular conditions&#xD;
      is not clear. No studies to the best of our knowledge compared Ketamine-based and&#xD;
      opioid-based protocols in rapid sequence induction of anesthesia in hemodynamically unstable&#xD;
      patients.&#xD;
&#xD;
      In this study, patients with severe sepsis or septic shock scheduled for surgery will be&#xD;
      assigned to receive either ketamine or fentanyl for induction of anesthesia. After induction&#xD;
      of anesthesia, endotracheal tube will be inserted aided by succinyl choline. Invasive blood&#xD;
      pressure will be monitored through a transducer connected to arterial catheter. Electrical&#xD;
      velocimetry (cardiometry) device will be used for non-invasive monitoring of cardiac output&#xD;
      and stroke volume.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 25, 2018</start_date>
  <completion_date type="Actual">December 30, 2019</completion_date>
  <primary_completion_date type="Actual">December 25, 2019</primary_completion_date>
  <phase>Phase 4</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean arterial pressure</measure>
    <time_frame>30 minutes after induction of anesthesia</time_frame>
    <description>Mean arterial blood pressure measured by invasive transducer attached to arterial catheter</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>cardiac output</measure>
    <time_frame>30 minutes after induction of anesthesia</time_frame>
    <description>cardiac output measured in litres per minute measured by electrical velocimetry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stroke volume</measure>
    <time_frame>30 minutes after induction of anesthesia</time_frame>
    <description>cardiac stroke volume in milliliters measured by electrical velocimetry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>heart rate</measure>
    <time_frame>30 minutes after induction of anesthesia</time_frame>
    <description>heart rate measured in beat per minute</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>serum lactate</measure>
    <time_frame>30 minutes after induction of anesthesia</time_frame>
    <description>serum lactate measured in mmol/liter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>total norepinephrine dose</measure>
    <time_frame>30 minutes after induction of anesthesia</time_frame>
    <description>total dose of norepinephrine measured in micrograms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intra-operative inhalational anesthetic concentration</measure>
    <time_frame>30 minutes</time_frame>
    <description>the concentration of inhalational anesthetic (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of post-induction hypotension</measure>
    <time_frame>5 minutes</time_frame>
    <description>The percent of patients with severe hypotension after induction of anesthesia requiring stoppage of inhalational anesthesia or increasing the dose of vasopressors</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Septic Shock</condition>
  <arm_group>
    <arm_group_label>Ketamine group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group of patients will receive: 1 mg/Kg ketamine + 0.05 mg/Kg midazolam for induction of anesthesia. Endotracheal tube will be inserted aided by 1 mg/Kg succinyl choline. Patients will undergo surgical procedure to eliminate the source of sepsis e.g. abdominal exploration. Invasive blood pressure monitor will be connected to the patient through an arterial catheter. Electrical velocimetry (cardiometry) device will be connected to the patient to measure cardiac output, stroke volume, and systemic vascular resistance.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fentanyl</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2.5 mg/Kg fentanyl + 0.05 mg/Kg midazolam for induction of anesthesia. Endotracheal tube will be inserted aided by 1 mg/Kg succinyl choline. Patients will undergo surgical procedure to eliminate the source of sepsis e.g. abdominal exploration. Invasive blood pressure monitor will be connected to the patient through an arterial catheter. Electrical velocimetry (cardiometry) device will be connected to the patient to measure cardiac output, stroke volume, and systemic vascular resistance.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>Patients will receive :1 mg/Kg ketamine for induction of anesthesia</description>
    <arm_group_label>Ketamine group</arm_group_label>
    <other_name>Katalar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl</intervention_name>
    <description>Patients will receive :2.5 mcg/Kg fentanyl for induction of anesthesia</description>
    <arm_group_label>Fentanyl</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <description>Patients will receive 0.05 mg/Kg midazolam</description>
    <arm_group_label>Fentanyl</arm_group_label>
    <arm_group_label>Ketamine group</arm_group_label>
    <other_name>Dormicum</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Sepsis patients&#xD;
&#xD;
          -  With shock index (heart rate divided by systolic blood pressure) &gt;0.7. or Sepsis&#xD;
             patients with norepinephrine infusion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Traumatic brain injury&#xD;
&#xD;
          -  Cerebrovascular disorders&#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>Ahmed Mukhtar</last_name>
    <role>Study Director</role>
    <affiliation>Head of research committee section in anesthesia department</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cairo University</name>
      <address>
        <city>Cairo</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>August 12, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>January 25, 2020</last_update_submitted>
  <last_update_submitted_qc>January 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cairo University</investigator_affiliation>
    <investigator_full_name>Ahmed Hasanin</investigator_full_name>
    <investigator_title>Assistant professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Shock, Septic</mesh_term>
    <mesh_term>Shock</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Ketamine</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/NCT03251170
org study id: N-12-2018
nct id: NCT03251170
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this work is to compare two protocols (ketamine-midazolam versus
      fentanyl-midazolam) for induction of anesthesia in patients with septic shock aiming to find
      the most safe protocol with regards to hemodynamic status of patients
Induction of anesthesia in hemodynamically compromised patients is a challenge for every
      anesthetist. Most of the intravenous induction agents have a negative effect on arterial
      blood pressure and cardiac output. Theoretically, the "ideal" emergency induction intravenous
      anesthetic should achieve rapid hypnosis and maintain the hemodynamic stability.

      Ketamine has been reported as an induction anesthetic with a sympathomimetic activity. In
      patients with intact autonomic nervous system ketamine increases heart rate, cardiac output,
      and arterial blood pressure (ABP). Despite its sympathomimetic activity in hemodynamically
      stable patients, the hemodynamic response to ketamine in unstable cardiovascular conditions
      is not clear. No studies to the best of our knowledge compared Ketamine-based and
      opioid-based protocols in rapid sequence induction of anesthesia in hemodynamically unstable
      patients.

      In this study, patients with severe sepsis or septic shock scheduled for surgery will be
      assigned to receive either ketamine or fentanyl for induction of anesthesia. After induction
      of anesthesia, endotracheal tube will be inserted aided by succinyl choline. Invasive blood
      pressure will be monitored through a transducer connected to arterial catheter. Electrical
      velocimetry (cardiometry) device will be used for non-invasive monitoring of cardiac output
      and stroke volume.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean arterial pressure
time frame: 30 minutes after induction of anesthesia
description: Mean arterial blood pressure measured by invasive transducer attached to arterial catheter
measure: cardiac output
time frame: 30 minutes after induction of anesthesia
description: cardiac output measured in litres per minute measured by electrical velocimetry
measure: Stroke volume
time frame: 30 minutes after induction of anesthesia
description: cardiac stroke volume in milliliters measured by electrical velocimetry
measure: heart rate
time frame: 30 minutes after induction of anesthesia
description: heart rate measured in beat per minute
measure: serum lactate
time frame: 30 minutes after induction of anesthesia
description: serum lactate measured in mmol/liter
measure: total norepinephrine dose
time frame: 30 minutes after induction of anesthesia
description: total dose of norepinephrine measured in micrograms
measure: Intra-operative inhalational anesthetic concentration
time frame: 30 minutes
description: the concentration of inhalational anesthetic (%)
measure: Incidence of post-induction hypotension
time frame: 5 minutes
description: The percent of patients with severe hypotension after induction of anesthesia requiring stoppage of inhalational anesthesia or increasing the dose of vasopressors
arm group label: Ketamine group
arm group type: Experimental
description: This group of patients will receive: 1 mg/Kg ketamine + 0.05 mg/Kg midazolam for induction of anesthesia. Endotracheal tube will be inserted aided by 1 mg/Kg succinyl choline. Patients will undergo surgical procedure to eliminate the source of sepsis e.g. abdominal exploration. Invasive blood pressure monitor will be connected to the patient through an arterial catheter. Electrical velocimetry (cardiometry) device will be connected to the patient to measure cardiac output, stroke volume, and systemic vascular resistance.
arm group label: Fentanyl
arm group type: Active Comparator
description: 2.5 mg/Kg fentanyl + 0.05 mg/Kg midazolam for induction of anesthesia. Endotracheal tube will be inserted aided by 1 mg/Kg succinyl choline. Patients will undergo surgical procedure to eliminate the source of sepsis e.g. abdominal exploration. Invasive blood pressure monitor will be connected to the patient through an arterial catheter. Electrical velocimetry (cardiometry) device will be connected to the patient to measure cardiac output, stroke volume, and systemic vascular resistance.
intervention type: Drug
intervention name: Ketamine
description: Patients will receive :1 mg/Kg ketamine for induction of anesthesia
arm group label: Ketamine group
other name: Katalar
intervention type: Drug
intervention name: Fentanyl
description: Patients will receive :2.5 mcg/Kg fentanyl for induction of anesthesia
arm group label: Fentanyl
intervention type: Drug
intervention name: Midazolam
description: Patients will receive 0.05 mg/Kg midazolam
arm group label: Fentanyl
arm group label: Ketamine group
other name: Dormicum
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Ahmed Mukhtar
role: Study Director
affiliation: Head of research committee section in anesthesia department
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Cairo University
investigator full name: Ahmed Hasanin
investigator title: Assistant professor
mesh term: Shock, Septic
mesh term: Shock
mesh term: Fentanyl
mesh term: Midazolam
mesh term: Ketamine
sharing ipd: No