<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/NCT04486690</url>
  </required_header>
  <id_info>
    <org_study_id>(MS/16.05.63)</org_study_id>
    <nct_id>NCT04486690</nct_id>
  </id_info>
  <brief_title>Neuroprotection During Open Heart Surgery</brief_title>
  <official_title>Neuroprotection During Open Heart Surgery Propofol Versus Ketofol</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ghada fouad</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mansoura University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Millions of individuals with coronary artery, or valvular heart disease have been given a new&#xD;
      chance at life by heart surgery, but the potential for neurological injury is a great risk&#xD;
      .Neural complications - including neurocognitive dysfunction and ischemic complications are&#xD;
      complications of cardiac surgery that can restrict the improved quality of life.&#xD;
&#xD;
      Propofol is one of the most popular agents used for induction of anesthesia. propofol reduces&#xD;
      cerebral blood flow but maintains coupling with cerebral metabolic rate for oxygen and&#xD;
      decreases intracranial pressure, allowing optimal intraoperative conditions.&#xD;
&#xD;
      Ketamine is a non-competitive antagonist of NMDA receptors that has well documented&#xD;
      neuroprotective effects against ischemic brain injury and glutamate-induced brain injury.&#xD;
      ketamine has neuroprotective effects against oxygen-glucose deprivation injury&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of the study is to evaluate neuroprotective effect of mixture of propofol and&#xD;
      ketamine (ketofol) as compared to propofol after open heart surgery.&#xD;
&#xD;
      Induction;&#xD;
&#xD;
        -  Pre-oxygenation with100% O2 for 3 min.&#xD;
&#xD;
        -  Morphine 0.1-0.15 mg/kg&#xD;
&#xD;
        -  Fentanyl, dose 3-5 mcg/kg.&#xD;
&#xD;
        -  hypnotic agent differs for each group:&#xD;
&#xD;
        -  Propofol group: Propofol, dose 0.5-2 mg/kg.&#xD;
&#xD;
        -  Ketofol group: Ketofol,( dose 0.25-1 mg/kg propofol plus 0.25-1 mg/kg ketamine diluted&#xD;
           in normal saline with maintained 1:1 ratio between propofol and ketamine. )&#xD;
&#xD;
      Catheterization:&#xD;
&#xD;
        1. Central venous catheter: A suitable central venous catheter will be inserted into Right&#xD;
           subclavian vein under complete aseptic technique using seldinger technique.&#xD;
&#xD;
        2. Jugular bulb catheterization: Patients is placed in supine position with mild neck&#xD;
           extension. The head is placed in neutral position with mild tilt to the opposite side of&#xD;
           insertion. Under complete aseptic conditions, the anatomical landmarks for the right&#xD;
           internal jugular vein will be identified (at the level of cricoid cartilage, medial to&#xD;
           the sternomastoid muscle and lateral to a palpable internal carotid artery). The&#xD;
           internal jugular vein will be then cannulated by retrograde insertion of a catheter for&#xD;
           sampling of the jugular venous bulb blood. Catheter will be advanced till resistance of&#xD;
           the skull base is reached then withdrawn about 1 to 2 mm.&#xD;
&#xD;
      Position of the catheter will be confirmed by antero-posterior and lateral neck C-arm x-ray&#xD;
      to verify the correct placement of the catheter tip in the will be sutured to the skin and&#xD;
      dressed with sterile gauze&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2016</start_date>
  <completion_date type="Actual">June 30, 2017</completion_date>
  <primary_completion_date type="Actual">June 30, 2017</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>2 groups of patients subjected to open heart surgery : Propofol group: Propofol, dose 0.5-2 mg/kg.&#xD;
Ketofol group: Ketofol,( dose 0.25-1 mg/kg propofol plus 0.25-1 mg/kg ketamine diluted in normal saline with maintained 1:1 ratio between propofol and ketamine. )</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>- Double blind study</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Cerebral oxygenation</measure>
    <time_frame>from start of surgery and for 24 hours postoperative</time_frame>
    <description>Cerebral oxygenation as indicated by calculation of:&#xD;
Arterio-Jugular oxygen content difference.&#xD;
Estimated cerebral metabolic rate for O2(eCMRO2) eCMRO2=Ca- jO2 x(PaCO2 ∕ 100) Where ……. Ca jO2 is arterio-jugular O2 content difference.&#xD;
PaCO2 is arterial CO2 tension</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>blood pressure measurement</measure>
    <time_frame>from start of surgery and for 24 hours postoperative</time_frame>
    <description>measurement of invasive blood pressure</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Open Heart Surgery</condition>
  <arm_group>
    <arm_group_label>propofol group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Propofol infusion, 25-150mic/kg/min.&#xD;
Fentanyl infusion, 1-2 mcg/kg/h.&#xD;
Atracurium infusion, 3-12 mic/kg/min</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ketofol group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ketofol 25-150 mic/kg/min with propofol to ketamine ratio 1:1.&#xD;
Fentanyl infusion, 1-2 mcg/kg/h.&#xD;
Atracurium infusion, 3-12 mic/kg/min</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketofol (propofol to ketamine ratio 1:1)</intervention_name>
    <description>Ketofol 25-150 mic/kg/min with propofol to ketamine ratio 1:1.&#xD;
Fentanyl infusion, 1-2 mcg/kg/h.&#xD;
Atracurium infusion, 3-12 mic/kg/min</description>
    <arm_group_label>ketofol group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>propofol</intervention_name>
    <description>Propofol infusion, 25-150 mcg/kg/min.&#xD;
Fentanyl infusion, 1-2 mcg/kg/h.&#xD;
Atracurium infusion, 3-12 mic/kg/min.</description>
    <arm_group_label>propofol group</arm_group_label>
    <other_name>deprivan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:Age between 30 and 70 years of either sex.&#xD;
&#xD;
          -  Patients scheduled for elective cardiac surgery using cardiopulmonary bypass (CPB)&#xD;
             either valve surgery or coronary artery bypass surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient refusal.&#xD;
&#xD;
          -  Morbidly obese patients.&#xD;
&#xD;
          -  Patients with uncontrolled diabetes.&#xD;
&#xD;
          -  Patients with pre-existing neurological disease or using anti-psychotics. Severe or&#xD;
             uncontrolled renal, hepatic or endocrinal diseases.&#xD;
&#xD;
          -  Pregnancy, post-partum or lactating females&#xD;
&#xD;
          -  Allergy to one of the agents used.&#xD;
&#xD;
          -  Emergency cardiac surgery.&#xD;
&#xD;
          -  Re-do surgery.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>mona a hashish, M.D</last_name>
    <role>Study Chair</role>
    <affiliation>professor of anesthesia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>ahmed m elshamy, master</last_name>
    <role>Principal Investigator</role>
    <affiliation>assistant lecturer of anesthesia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>ghada f amer, M.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>associate professor of anesthesia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>magdy m attalaha, M.D</last_name>
    <role>Study Chair</role>
    <affiliation>professor of anethesia</affiliation>
  </overall_official>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>July 23, 2020</last_update_submitted>
  <last_update_submitted_qc>July 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Mansoura University</investigator_affiliation>
    <investigator_full_name>ghada fouad</investigator_full_name>
    <investigator_title>associate professor of anesthesia</investigator_title>
  </responsible_party>
  <keyword>propofol</keyword>
  <keyword>ketofol</keyword>
  <keyword>neuroprotection</keyword>
  <keyword>open heart surgery</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
    <mesh_term>Propofol</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/NCT04486690
org study id: (MS/16.05.63)
nct id: NCT04486690
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Millions of individuals with coronary artery, or valvular heart disease have been given a new
      chance at life by heart surgery, but the potential for neurological injury is a great risk
      .Neural complications - including neurocognitive dysfunction and ischemic complications are
      complications of cardiac surgery that can restrict the improved quality of life.

      Propofol is one of the most popular agents used for induction of anesthesia. propofol reduces
      cerebral blood flow but maintains coupling with cerebral metabolic rate for oxygen and
      decreases intracranial pressure, allowing optimal intraoperative conditions.

      Ketamine is a non-competitive antagonist of NMDA receptors that has well documented
      neuroprotective effects against ischemic brain injury and glutamate-induced brain injury.
      ketamine has neuroprotective effects against oxygen-glucose deprivation injury
The aim of the study is to evaluate neuroprotective effect of mixture of propofol and
      ketamine (ketofol) as compared to propofol after open heart surgery.

      Induction;

        -  Pre-oxygenation with100% O2 for 3 min.

        -  Morphine 0.1-0.15 mg/kg

        -  Fentanyl, dose 3-5 mcg/kg.

        -  hypnotic agent differs for each group:

        -  Propofol group: Propofol, dose 0.5-2 mg/kg.

        -  Ketofol group: Ketofol,( dose 0.25-1 mg/kg propofol plus 0.25-1 mg/kg ketamine diluted
           in normal saline with maintained 1:1 ratio between propofol and ketamine. )

      Catheterization:

        1. Central venous catheter: A suitable central venous catheter will be inserted into Right
           subclavian vein under complete aseptic technique using seldinger technique.

        2. Jugular bulb catheterization: Patients is placed in supine position with mild neck
           extension. The head is placed in neutral position with mild tilt to the opposite side of
           insertion. Under complete aseptic conditions, the anatomical landmarks for the right
           internal jugular vein will be identified (at the level of cricoid cartilage, medial to
           the sternomastoid muscle and lateral to a palpable internal carotid artery). The
           internal jugular vein will be then cannulated by retrograde insertion of a catheter for
           sampling of the jugular venous bulb blood. Catheter will be advanced till resistance of
           the skull base is reached then withdrawn about 1 to 2 mm.

      Position of the catheter will be confirmed by antero-posterior and lateral neck C-arm x-ray
      to verify the correct placement of the catheter tip in the will be sutured to the skin and
      dressed with sterile gauze
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 2 groups of patients subjected to open heart surgery : Propofol group: Propofol, dose 0.5-2 mg/kg.
Ketofol group: Ketofol,( dose 0.25-1 mg/kg propofol plus 0.25-1 mg/kg ketamine diluted in normal saline with maintained 1:1 ratio between propofol and ketamine. )
primary purpose: Supportive Care
masking: Double (Participant, Investigator)
masking description: - Double blind study
measure: Cerebral oxygenation
time frame: from start of surgery and for 24 hours postoperative
description: Cerebral oxygenation as indicated by calculation of:
Arterio-Jugular oxygen content difference.
Estimated cerebral metabolic rate for O2(eCMRO2) eCMRO2=Ca- jO2 x(PaCO2 ∕ 100) Where ……. Ca jO2 is arterio-jugular O2 content difference.
PaCO2 is arterial CO2 tension
measure: blood pressure measurement
time frame: from start of surgery and for 24 hours postoperative
description: measurement of invasive blood pressure
arm group label: propofol group
arm group type: Experimental
description: Propofol infusion, 25-150mic/kg/min.
Fentanyl infusion, 1-2 mcg/kg/h.
Atracurium infusion, 3-12 mic/kg/min
arm group label: ketofol group
arm group type: Active Comparator
description: Ketofol 25-150 mic/kg/min with propofol to ketamine ratio 1:1.
Fentanyl infusion, 1-2 mcg/kg/h.
Atracurium infusion, 3-12 mic/kg/min
intervention type: Drug
intervention name: Ketofol (propofol to ketamine ratio 1:1)
description: Ketofol 25-150 mic/kg/min with propofol to ketamine ratio 1:1.
Fentanyl infusion, 1-2 mcg/kg/h.
Atracurium infusion, 3-12 mic/kg/min
arm group label: ketofol group
intervention type: Drug
intervention name: propofol
description: Propofol infusion, 25-150 mcg/kg/min.
Fentanyl infusion, 1-2 mcg/kg/h.
Atracurium infusion, 3-12 mic/kg/min.
arm group label: propofol group
other name: deprivan
criteria: 
gender: All
minimum age: 30 Years
maximum age: 70 Years
healthy volunteers: No
last name: mona a hashish, M.D
role: Study Chair
affiliation: professor of anesthesia
last name: ahmed m elshamy, master
role: Principal Investigator
affiliation: assistant lecturer of anesthesia
last name: ghada f amer, M.D
role: Principal Investigator
affiliation: associate professor of anesthesia
last name: magdy m attalaha, M.D
role: Study Chair
affiliation: professor of anethesia
responsible party type: Sponsor-Investigator
investigator affiliation: Mansoura University
investigator full name: ghada fouad
investigator title: associate professor of anesthesia
mesh term: Ketamine
mesh term: Propofol
sharing ipd: No