<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/NCT03769142</url>
  </required_header>
  <id_info>
    <org_study_id>SRLF 11-356</org_study_id>
    <nct_id>NCT03769142</nct_id>
  </id_info>
  <brief_title>Cerebral Perfusion During Induction of General Anesthesia</brief_title>
  <official_title>Cerebral Perfusion Changes During General Anesthesia Induction: Relation Between Transcranial Doppler, Bispectral Index and Cerebral Oximetry: a Prospective Observational Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>INSERM UMR-942, Paris, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Department of Anesthesiology, Hopital Foch, Suresnes, France.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>M3DISIM</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ouctomes Research Consortium, Cleveland Clinic, Ohio, USA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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>
      Arterial hypotension during general anesthesia remains a factor of poor outcomes, increases&#xD;
      the risk of myocardial infarction, acute kidney injury and 1-year mortality. Furthermore,&#xD;
      arterial hypotension may also decrease cerebral perfusion contributing to worsen neurological&#xD;
      outcome. It seems necessary to monitor cerebral perfusion during anesthesia and to define&#xD;
      individual dynamic targets of blood pressure. The goal of this study is to evaluate cerebral&#xD;
      perfusion change in adult patients with or without cardiovascular risk factors during a&#xD;
      standardized propofol-remifentanil anesthesia induction. Cerebral perfusion will be evaluated&#xD;
      and compared using the simultaneously measure of TCD, NIRS and BIS. Those measures will be&#xD;
      also repeated during and after treatment of arterial hypotension episodes in both groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Main objective : the blood pressure target to maintain cerebral perfusion is related to&#xD;
      patient´s characteristics or comorbidities and it remains uncertain which threshold of blood&#xD;
      pressure to use during general anesthesia. Thus, it seems necessary to monitor cerebral&#xD;
      perfusion during anesthesia and to define individual dynamic targets of blood pressure. The&#xD;
      measure of middle cerebral artery blood flow velocity by transcranial doppler (TCD) is a&#xD;
      clinical method to assess cerebral perfusion during general anesthesia and several studies&#xD;
      have reported the hemodynamic impact on cerebral blood flow during induction.&#xD;
&#xD;
      Cerebral perfusion can also be approached by near infrared spectroscopy (NIRS) which measures&#xD;
      continuously cerebral oxygen saturation.&#xD;
&#xD;
      Bispectral index (BIS) which allows a simplified form of continuous electroencephalogram&#xD;
      monitoring to assess depth of anesthesia could also report cerebral hypoperfusion quantified&#xD;
      by the count of burst suppression ratio (SR). Potentially, those tools need to be combined to&#xD;
      assess cerebral perfusion properly.&#xD;
&#xD;
      The goal of this study is to evaluate cerebral perfusion change in adult participants with or&#xD;
      without cardiovascular risk factors during a standardized propofol-remifentanil anesthesia&#xD;
      induction. Cerebral perfusion was evaluated and compared using the simultaneously measure of&#xD;
      TCD, NIRS and BIS. Those measures will be also repeated during and after treatment of&#xD;
      arterial hypotension episodes in both groups.&#xD;
&#xD;
      Experimental design : this is a single-center, interventional, category II prospective study&#xD;
      (minimal risks and constraints) Population concerned :the study involves major patients who&#xD;
      beneficiate from intraoperative hemodynamic optimization with norepinephrine (as&#xD;
      noradrenaline tartrate) for maintaining blood pressure under general anaesthesia in&#xD;
      interventional neuroradiology in adults.&#xD;
&#xD;
      Research Proceedings : all monitoring (TCD, BIS, NIRS) are collected from the healthy side,&#xD;
      contralateral to the interventional side. BIS, NIRS and continuous non-invasive blood&#xD;
      pressure are all connected to the main monitor. For all participants, data from TCD, NIRS,&#xD;
      BIS and hemodynamic data are collected at three distinct periods the day of the procedure :&#xD;
      (1) baseline or during pre-oxygenation at FiO2 21% (inspiratory fraction oxygen) in awake&#xD;
      patients, (2) before Orotracheal Intubation and (3) just after mechanical ventilation.&#xD;
&#xD;
      In patients presenting a hypotensive episode at any time of the procedure, all parameters are&#xD;
      collected before and at the peak effect of a 10µg bolus of norepinephrine Individual&#xD;
      benefit:there is no benefit for the patient&#xD;
&#xD;
      Collective benefit: It seems necessary to monitor cerebral perfusion during anesthesia and to&#xD;
      define individual dynamic targets of blood pressure. During general anesthesia, cerebral&#xD;
      perfusion can be impaired and requires specific monitoring.&#xD;
&#xD;
      Risks and minimal constraints added by the research : no added risk. This clinical research&#xD;
      work is &quot;non-interventional&quot; on adult patients who benefit from a neuroradiological&#xD;
      intervention. All measures are obtained non-invasively.&#xD;
&#xD;
      Patients were assigned to one of two groups according to cardiovascular risk factors. Major&#xD;
      risk factor was age &gt; 50 years old and minor risk factors were history of congestive heart&#xD;
      failure, history of cardiovascular event, current smoking, diabetes mellitus, dyslipidemia,&#xD;
      arterial hypertension.&#xD;
&#xD;
      Patients will be classified into the high-risk group (Hi-risk) if they have at least one&#xD;
      major criterion or two minor criteria or into the low risk group (Lo-risk) if they present&#xD;
      with no or one minor criterion.&#xD;
&#xD;
      During their interventional neuroradiology procedure, all patients' routine monitoring will&#xD;
      consist of electrocardiogram, pulsated oxygen saturation, end-tidal C02 (carbon dioxide),&#xD;
      respiratory rate, tidal volume and monitoring of neuromuscular function.&#xD;
&#xD;
      For all patients whatever the comorbidities, anesthesia induction will be performed using a&#xD;
      target-controlled infusion (Orchestra® Base Primea - Fresenius Kabi France).&#xD;
&#xD;
      According to our standard of care, intra-operative episodes of hypotension (mean arterial&#xD;
      pressure (MAP) &lt; 65 mmHg or &lt; 80% baseline) were treated by Norepinephrine bolus of 10 µg.&#xD;
&#xD;
      For all patients, data from TCD, NIRS, BIS and hemodynamic data will be collected at three&#xD;
      distinct periods: (1) Baseline or during pre-oxygenation at FiO2 21% (Inspiratory Fraction&#xD;
      Oxygen) in awake patients, (2) Before Orotracheal Intubation and (3) just after mechanical&#xD;
      ventilation.&#xD;
&#xD;
      In patients presenting a hypotensive episode at any time of the procedure, all parameters&#xD;
      were collected before and at the peak effect of a 10µg bolus of norepinephrine.&#xD;
&#xD;
      Number of selected subjects : Selection of patients up to 100 analysable patients Number of&#xD;
      Centre : 1 Research Agenda inclusion period: 24 months Duration of participation (treatment +&#xD;
      follow-up): duration of the interventional neuroradiology procedure so maximum 1 day Total&#xD;
      duration: 24 months Number of planned inclusions by centre and month : 5 Number of subjects&#xD;
      required : 100&#xD;
&#xD;
      Statistics&#xD;
&#xD;
      Changes of parameters across time, during induction and/or during vasopressors boluses will&#xD;
      be tested by using a paired Student-t test after testing the normality of distribution.&#xD;
      Correlation between change of MAP and Vm during induction will be done using Spearman test.&#xD;
      Complete analysis will also be performed and compared between Low-risk and High-risk&#xD;
      patients. The analysis of vasopressor boluses will also be performed according to the time of&#xD;
      the administration: boluses which are given immediately after induction of anesthesia (early)&#xD;
      and boluses given after a 30 minutes period of constant intra-venous calculated&#xD;
      concentrations of anesthesia (late). All statistical analyses were performed using R&#xD;
      statistical software (The 'R' Foundation for Statistical Computing, Vienna, Austria). Results&#xD;
      are expressed as means (± SD). A two-sided p value of 0.05 was considered significant.&#xD;
&#xD;
      The sample size calculation is based on the following assumptions: incidence of Hi-risk&#xD;
      patients of 50%, as previously reported, incidence of burst suppression during induction in&#xD;
      low risk patients of 20% difference of incidence of burst suppression between low- and&#xD;
      high-risk patients at 30%, power at 80% and type I error at 5%. Accordingly, the calculated&#xD;
      sample size is 100 patients for the entire population.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2014</start_date>
  <completion_date type="Actual">December 1, 2016</completion_date>
  <primary_completion_date type="Actual">December 1, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Continuous measure of mean arterial pressure in mmHg (MAP)</measure>
    <time_frame>Duration of the surgical intervention or interventional neuroradiology procedure (maximum 1 day)</time_frame>
    <description>For all patients, mean arterial pressure will be collected at three distinct periods: (1) Baseline or during pre-oxygenation at FiO2 21% in awake patients, (2) Before Orotracheal Intubation and (3) just after mechanical ventilation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measure of cerebral blood flow (CFV in cm/s) with Transcranial Doppler</measure>
    <time_frame>Duration of the surgical intervention or interventional neuroradiology procedure (maximum 1 day)</time_frame>
    <description>For all patients, cerebral flow velocity will be collected at three distinct periods: (1) Baseline or during pre-oxygenation at FiO2 21% in awake patients, (2) Before Orotracheal Intubation and (3) just after mechanical ventilation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Continuous measure of Burst Suppression (BS in %) with Bispectral Index (BIS)</measure>
    <time_frame>Duration of the surgical intervention or interventional neuroradiology procedure (maximum 1 day)</time_frame>
    <description>For all patients, Burst Supression will be collected at three distinct periods: (1) Baseline or during pre-oxygenation at FiO2 21% in awake patients, (2) Before Orotracheal Intubation and (3) just after mechanical ventilation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Continuous measure of cerebral oxygen saturation (SO2 in %) with Near-infrared spectroscopy (NIRS)</measure>
    <time_frame>Duration of the surgical intervention or interventional neuroradiology procedure (maximum 1 day)</time_frame>
    <description>For all patients, cerebral oxygen saturation will be collected at three distinct periods: (1) Baseline or during pre-oxygenation at FiO2 21% in awake patients, (2) Before Orotracheal Intubation and (3) just after mechanical ventilation.</description>
  </primary_outcome>
  <enrollment type="Actual">100</enrollment>
  <condition>Radiography</condition>
  <condition>Interventional</condition>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>All monitoring</intervention_name>
    <description>All monitoring (TCD, BIS, NIRS) are collected from the healthy side, contralateral to the interventional side</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        patients with scheduled an elective interventional neuroradiology procedure requiring&#xD;
        general anesthesia&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients &gt; 18 years, scheduled an elective interventional neuroradiology procedure&#xD;
             requiring general anesthesia&#xD;
&#xD;
          -  oral agreement obtained from each patient before anesthesia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age &lt;18 years&#xD;
&#xD;
          -  an emergency procedure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joaquim MATEO, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>October 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>December 6, 2018</last_update_submitted>
  <last_update_submitted_qc>December 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cerebral perfusion</keyword>
  <keyword>hypotension</keyword>
  <keyword>transcranial Doppler</keyword>
  <keyword>general anesthesia</keyword>
  <keyword>Bispectral Index</keyword>
  <keyword>Near-infrared spectroscopy (NIRS)</keyword>
  <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/NCT03769142
org study id: SRLF 11-356
nct id: NCT03769142
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Arterial hypotension during general anesthesia remains a factor of poor outcomes, increases
      the risk of myocardial infarction, acute kidney injury and 1-year mortality. Furthermore,
      arterial hypotension may also decrease cerebral perfusion contributing to worsen neurological
      outcome. It seems necessary to monitor cerebral perfusion during anesthesia and to define
      individual dynamic targets of blood pressure. The goal of this study is to evaluate cerebral
      perfusion change in adult patients with or without cardiovascular risk factors during a
      standardized propofol-remifentanil anesthesia induction. Cerebral perfusion will be evaluated
      and compared using the simultaneously measure of TCD, NIRS and BIS. Those measures will be
      also repeated during and after treatment of arterial hypotension episodes in both groups.
Main objective : the blood pressure target to maintain cerebral perfusion is related to
      patient´s characteristics or comorbidities and it remains uncertain which threshold of blood
      pressure to use during general anesthesia. Thus, it seems necessary to monitor cerebral
      perfusion during anesthesia and to define individual dynamic targets of blood pressure. The
      measure of middle cerebral artery blood flow velocity by transcranial doppler (TCD) is a
      clinical method to assess cerebral perfusion during general anesthesia and several studies
      have reported the hemodynamic impact on cerebral blood flow during induction.

      Cerebral perfusion can also be approached by near infrared spectroscopy (NIRS) which measures
      continuously cerebral oxygen saturation.

      Bispectral index (BIS) which allows a simplified form of continuous electroencephalogram
      monitoring to assess depth of anesthesia could also report cerebral hypoperfusion quantified
      by the count of burst suppression ratio (SR). Potentially, those tools need to be combined to
      assess cerebral perfusion properly.

      The goal of this study is to evaluate cerebral perfusion change in adult participants with or
      without cardiovascular risk factors during a standardized propofol-remifentanil anesthesia
      induction. Cerebral perfusion was evaluated and compared using the simultaneously measure of
      TCD, NIRS and BIS. Those measures will be also repeated during and after treatment of
      arterial hypotension episodes in both groups.

      Experimental design : this is a single-center, interventional, category II prospective study
      (minimal risks and constraints) Population concerned :the study involves major patients who
      beneficiate from intraoperative hemodynamic optimization with norepinephrine (as
      noradrenaline tartrate) for maintaining blood pressure under general anaesthesia in
      interventional neuroradiology in adults.

      Research Proceedings : all monitoring (TCD, BIS, NIRS) are collected from the healthy side,
      contralateral to the interventional side. BIS, NIRS and continuous non-invasive blood
      pressure are all connected to the main monitor. For all participants, data from TCD, NIRS,
      BIS and hemodynamic data are collected at three distinct periods the day of the procedure :
      (1) baseline or during pre-oxygenation at FiO2 21% (inspiratory fraction oxygen) in awake
      patients, (2) before Orotracheal Intubation and (3) just after mechanical ventilation.

      In patients presenting a hypotensive episode at any time of the procedure, all parameters are
      collected before and at the peak effect of a 10µg bolus of norepinephrine Individual
      benefit:there is no benefit for the patient

      Collective benefit: It seems necessary to monitor cerebral perfusion during anesthesia and to
      define individual dynamic targets of blood pressure. During general anesthesia, cerebral
      perfusion can be impaired and requires specific monitoring.

      Risks and minimal constraints added by the research : no added risk. This clinical research
      work is "non-interventional" on adult patients who benefit from a neuroradiological
      intervention. All measures are obtained non-invasively.

      Patients were assigned to one of two groups according to cardiovascular risk factors. Major
      risk factor was age > 50 years old and minor risk factors were history of congestive heart
      failure, history of cardiovascular event, current smoking, diabetes mellitus, dyslipidemia,
      arterial hypertension.

      Patients will be classified into the high-risk group (Hi-risk) if they have at least one
      major criterion or two minor criteria or into the low risk group (Lo-risk) if they present
      with no or one minor criterion.

      During their interventional neuroradiology procedure, all patients' routine monitoring will
      consist of electrocardiogram, pulsated oxygen saturation, end-tidal C02 (carbon dioxide),
      respiratory rate, tidal volume and monitoring of neuromuscular function.

      For all patients whatever the comorbidities, anesthesia induction will be performed using a
      target-controlled infusion (Orchestra® Base Primea - Fresenius Kabi France).

      According to our standard of care, intra-operative episodes of hypotension (mean arterial
      pressure (MAP) < 65 mmHg or < 80% baseline) were treated by Norepinephrine bolus of 10 µg.

      For all patients, data from TCD, NIRS, BIS and hemodynamic data will be collected at three
      distinct periods: (1) Baseline or during pre-oxygenation at FiO2 21% (Inspiratory Fraction
      Oxygen) in awake patients, (2) Before Orotracheal Intubation and (3) just after mechanical
      ventilation.

      In patients presenting a hypotensive episode at any time of the procedure, all parameters
      were collected before and at the peak effect of a 10µg bolus of norepinephrine.

      Number of selected subjects : Selection of patients up to 100 analysable patients Number of
      Centre : 1 Research Agenda inclusion period: 24 months Duration of participation (treatment +
      follow-up): duration of the interventional neuroradiology procedure so maximum 1 day Total
      duration: 24 months Number of planned inclusions by centre and month : 5 Number of subjects
      required : 100

      Statistics

      Changes of parameters across time, during induction and/or during vasopressors boluses will
      be tested by using a paired Student-t test after testing the normality of distribution.
      Correlation between change of MAP and Vm during induction will be done using Spearman test.
      Complete analysis will also be performed and compared between Low-risk and High-risk
      patients. The analysis of vasopressor boluses will also be performed according to the time of
      the administration: boluses which are given immediately after induction of anesthesia (early)
      and boluses given after a 30 minutes period of constant intra-venous calculated
      concentrations of anesthesia (late). All statistical analyses were performed using R
      statistical software (The 'R' Foundation for Statistical Computing, Vienna, Austria). Results
      are expressed as means (± SD). A two-sided p value of 0.05 was considered significant.

      The sample size calculation is based on the following assumptions: incidence of Hi-risk
      patients of 50%, as previously reported, incidence of burst suppression during induction in
      low risk patients of 20% difference of incidence of burst suppression between low- and
      high-risk patients at 30%, power at 80% and type I error at 5%. Accordingly, the calculated
      sample size is 100 patients for the entire population.
observational model: Other
time perspective: Prospective
measure: Continuous measure of mean arterial pressure in mmHg (MAP)
time frame: Duration of the surgical intervention or interventional neuroradiology procedure (maximum 1 day)
description: For all patients, mean arterial pressure will be collected at three distinct periods: (1) Baseline or during pre-oxygenation at FiO2 21% in awake patients, (2) Before Orotracheal Intubation and (3) just after mechanical ventilation
measure: Measure of cerebral blood flow (CFV in cm/s) with Transcranial Doppler
time frame: Duration of the surgical intervention or interventional neuroradiology procedure (maximum 1 day)
description: For all patients, cerebral flow velocity will be collected at three distinct periods: (1) Baseline or during pre-oxygenation at FiO2 21% in awake patients, (2) Before Orotracheal Intubation and (3) just after mechanical ventilation.
measure: Continuous measure of Burst Suppression (BS in %) with Bispectral Index (BIS)
time frame: Duration of the surgical intervention or interventional neuroradiology procedure (maximum 1 day)
description: For all patients, Burst Supression will be collected at three distinct periods: (1) Baseline or during pre-oxygenation at FiO2 21% in awake patients, (2) Before Orotracheal Intubation and (3) just after mechanical ventilation.
measure: Continuous measure of cerebral oxygen saturation (SO2 in %) with Near-infrared spectroscopy (NIRS)
time frame: Duration of the surgical intervention or interventional neuroradiology procedure (maximum 1 day)
description: For all patients, cerebral oxygen saturation will be collected at three distinct periods: (1) Baseline or during pre-oxygenation at FiO2 21% in awake patients, (2) Before Orotracheal Intubation and (3) just after mechanical ventilation.
intervention type: Procedure
intervention name: All monitoring
description: All monitoring (TCD, BIS, NIRS) are collected from the healthy side, contralateral to the interventional side
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joaquim MATEO, MD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
responsible party type: Sponsor
sharing ipd: Undecided