<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/NCT03756935</url>
  </required_header>
  <id_info>
    <org_study_id>JMATEO</org_study_id>
    <nct_id>NCT03756935</nct_id>
  </id_info>
  <brief_title>Early Detection of Intra Operative Hypotension (IOH) During the Induction of General Anaesthesia</brief_title>
  <official_title>Non-invasive and Continuous Detection of Arterial Hypotension Using Photoplethysmographic Signal During Induction of Anaesthesia: Proof of Concept</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hopital Lariboisière</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>INSERM UMR-942, Paris, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>M3DISIM</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hopital Lariboisière</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>
      During general anaesthesia, intraoperative hypotension (IOH), defined as a mean arterial&#xD;
      pressure (MAP) drop of more than 20%, is frequent with potential deleterious effects for&#xD;
      patients. Pulse oximeter is mandatory in the operating room making photoplethysmographic&#xD;
      (PPG) signal and parameters such as the relative dicrotic notch height (Dicpleth) or the&#xD;
      perfusion index (PI) readily available. The purpose of this study is to investigate whether&#xD;
      Dicpleth and PI could detect IOH during anaesthesia induction and follow their variations&#xD;
      during vasopressor boluses.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Main objective Haemodynamic stability is a major issue in the management of patients during&#xD;
      general anaesthesia. Anaesthetic drugs induce rapid and deep systemic arterial blood pressure&#xD;
      (ABP) drop which leads to intra operative hypotension (IOH) episodes. IOH can cause&#xD;
      deleterious consequences such as myocardial infraction, cerebral hypoperfusion or acute&#xD;
      kidney injury.&#xD;
&#xD;
      The major drawback of the oscillometric cuff is to measure ABP only at intermittent&#xD;
      intervals. As ABP may vary quickly, especially during induction of anaesthesia, IOH should be&#xD;
      detected in real time as even a short period of IOH may have deleterious consequences on&#xD;
      vital organs.&#xD;
&#xD;
      Digital photoplethysmography (PPG) is a non-invasive signal produced by light absorption&#xD;
      variations due to pulsatile blood volume variations. Indices derived from PPG signals have&#xD;
      been used successfully to characterize cardiovascular state in patients.&#xD;
&#xD;
      Dicrotic notch height (Dicpleth), representing the relative height of the dicrotic wave&#xD;
      compared to the maximum peak of the waveform, has been described as the amount of reflected&#xD;
      wave, dependent of the vascular tone. Reduction in Dicpleth has been shown to be related to&#xD;
      reduction of vascular tone due to vasodilator drugs such as salbutamol or glyceryl&#xD;
      Trinitrate.&#xD;
&#xD;
      Perfusion Index (PI) represents the ratio of the pulsatile light absorption (i.e the amount&#xD;
      of blood ejected at each systole) on the continuous absorption (corresponding to the&#xD;
      non-pulsatile vessels, bones and soft tissues). PI has been described as a reliable tool for&#xD;
      vascular tone assessment and monitoring&#xD;
&#xD;
      Primary Evaluation Criteria As Dicpleth and PI are both related to vascular tone and are&#xD;
      easily derived from the PPG signal, Investigators aimed to explore whether the combined&#xD;
      analysis of Dicpleth and PI variations would allow for early detection of IOH during the&#xD;
      during a standardized propofol-remifentanil anesthesia induction.&#xD;
&#xD;
      Estimate the correlations between variations of Dicpleth and MAP, and PI and MAP during&#xD;
      induction of anaesthesia and during bolus of vasopressors.&#xD;
&#xD;
      Estimate if a combined analysis of these two parameters enhanced diagnostic performance for&#xD;
      detecting IOH under actions of vasoactive effect of anaesthetics.&#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 Hemodynamic parameters (heart rate, systolic arterial pressure [SAP],&#xD;
      mean arterial pressure [MAP] and diastolic arterial pressure [DAP]), and PPG parameters&#xD;
      (Dicpleth, PI and SpO2) will be retrospectively sampled every minute during induction. All&#xD;
      monitoring parameters and curves displayed on the monitor will be recorded on a computer with&#xD;
      ixTrend© software (ixellence, Wildau, Germany). Investigators defined &quot;pre-pressor&quot; values as&#xD;
      the measures prior to the vasopressor bolus during IOH episodes. &quot;Peak-pressor&quot; values is&#xD;
      defined as the maximum effects of vasopressor bolus, when the highest MAP is reached. In&#xD;
      agreement with most studies, IOH is defined as a MAP drop of more than 20% from baseline MAP.&#xD;
&#xD;
      In patients presenting a hypotensive episode, all parameters are collected before and at the&#xD;
      peak effect of a 10µg bolus of norepinephrine&#xD;
&#xD;
      Individual benefit:&#xD;
&#xD;
      There is no benefit for the patient&#xD;
&#xD;
      Collective benefit:&#xD;
&#xD;
      As ABP may vary quickly, especially during induction of anaesthesia, IOH should be detected&#xD;
      in real time as even a short period of IOH may have deleterious consequences on vital organs.&#xD;
      The non-invasive combined analysis of Dicpleth and PI variations would allow for early&#xD;
      detection of IOH during the induction of general anaesthesia.&#xD;
&#xD;
      Risks and minimal constraints added by the research No added risk This clinical research work&#xD;
      is &quot;non-interventional&quot; on adult patients who benefit from a neuroradiological intervention.&#xD;
      All measures are obtained non-invasively.&#xD;
&#xD;
      During their interventional neuroradiology procedure, all patients' routine monitoring will&#xD;
      consist of electrocardiogram, pulsated oxygen saturation, end-tidal CO2, respiratory rate,&#xD;
      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;
      In agreement with most studies, IOH is defined as a MAP drop of more than 20% from baseline&#xD;
      MAP.&#xD;
&#xD;
      Hemodynamic parameters (heart rate, systolic arterial pressure [SAP], mean arterial pressure&#xD;
      [MAP] and diastolic arterial pressure [DAP]), and PPG parameters (Dicpleth, PI and SpO2) will&#xD;
      be retrospectively sampled every minute during induction.&#xD;
&#xD;
      In patients presenting a hypotensive episode, all parameters are collected before and at the&#xD;
      peak effect of a 10µg bolus of norepinephrine.&#xD;
&#xD;
      Number of selected subjects The primary aim of the study is to estimate the AUC of the ROC&#xD;
      curve of both ΔDicpleth and ΔPI to track IOH during induction. Sample size was determined&#xD;
      with an expected AUC at 0.85, an expected incidence of hypotension of 80% and the width of&#xD;
      the confidence interval of 1. With a power of 80%, the number of patients to include was then&#xD;
      62.15 Secondary objective is to evaluate AUC of the ROC curve for combination of ΔDicpleth&#xD;
      and ΔPI.&#xD;
&#xD;
      Statistics Changes of the parameters are analysed using Wilcoxon rank test. Correlation tests&#xD;
      between ΔDicpleth and ΔMAP in one hand, and ΔPI and ΔMAP are performed by using Spearman&#xD;
      test. Areas under the curve (AUC) of Receiver Operating Characteristic (ROC) curve (with 95%&#xD;
      confidence interval) of ΔDicpleth and ΔPI to detect IOH episode will be estimated and&#xD;
      eventually compared using DeLong test. Youden method is used to determine the optimal&#xD;
      ΔDicpleth and ΔPI cut-off values to detect IOH episodes. Values are expressed as median and&#xD;
      interquartile range [25th;75th percentiles]. P&lt;0.05 is considered as statistically&#xD;
      significant. Statistical analysis is performed using Prism 6.00© (Graphpad Software, Inc, La&#xD;
      Jolla, CA, USA) and R 3.3.0 software (R foundation for Statistical Computing, Vienna,&#xD;
      Austria).&#xD;
&#xD;
      Patients who have non-measurable Dicpleth at baseline before induction of anaesthesia will be&#xD;
      excluded from the analysis&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2014</start_date>
  <completion_date type="Actual">May 23, 2015</completion_date>
  <primary_completion_date type="Actual">May 23, 2015</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 (MAP in mmHg)</measure>
    <time_frame>Time Frame: duration of the interventional neuroradiology procedure: 1 day</time_frame>
    <description>We calculated the variation of MAP during the induction period from the relative variations (in percent) from their baseline values. During vasopressor boluses, respective parameter's variations are calculated between &quot;pre-pressor&quot; and &quot;peak-pressor&quot; measurements.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Continuous measure of SpO2 in % by photoplethysmography</measure>
    <time_frame>Time Frame: duration of the interventional neuroradiology procedure: 1 day</time_frame>
    <description>We calculated variations of Dicpleth, and perfusion index (PI) during the induction period from the relative variations (in percent) from their baseline values. During vasopressor boluses, respective parameter's variations are calculated between &quot;pre-pressor&quot; and &quot;peak-pressor&quot; measurements.</description>
  </primary_outcome>
  <enrollment type="Actual">62</enrollment>
  <condition>Radiography</condition>
  <condition>Interventional</condition>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>All monitoring</intervention_name>
    <description>Dicpleth and PI are obtained a posteriori from the PPG waveform reconstruction and blindly from ABP values. Dicpleth is defined as the ratio of the height of the dicrotic notch (from nadir point of the complex to the notch) to the height of the systolic peak (from nadir point of the complex to the pic), measured at end-expiratory time (average of 3 consecutive complex). PI is calculated as the ratio of the pulsatile component of the PPG signal and the continuous component.</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>Hopital Lariboisière</affiliation>
  </overall_official>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 16, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>November 27, 2018</last_update_submitted>
  <last_update_submitted_qc>November 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hopital Lariboisière</investigator_affiliation>
    <investigator_full_name>Joaquim MATEO</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypotension</mesh_term>
  </condition_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/NCT03756935
org study id: JMATEO
nct id: NCT03756935
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
During general anaesthesia, intraoperative hypotension (IOH), defined as a mean arterial
      pressure (MAP) drop of more than 20%, is frequent with potential deleterious effects for
      patients. Pulse oximeter is mandatory in the operating room making photoplethysmographic
      (PPG) signal and parameters such as the relative dicrotic notch height (Dicpleth) or the
      perfusion index (PI) readily available. The purpose of this study is to investigate whether
      Dicpleth and PI could detect IOH during anaesthesia induction and follow their variations
      during vasopressor boluses.
Main objective Haemodynamic stability is a major issue in the management of patients during
      general anaesthesia. Anaesthetic drugs induce rapid and deep systemic arterial blood pressure
      (ABP) drop which leads to intra operative hypotension (IOH) episodes. IOH can cause
      deleterious consequences such as myocardial infraction, cerebral hypoperfusion or acute
      kidney injury.

      The major drawback of the oscillometric cuff is to measure ABP only at intermittent
      intervals. As ABP may vary quickly, especially during induction of anaesthesia, IOH should be
      detected in real time as even a short period of IOH may have deleterious consequences on
      vital organs.

      Digital photoplethysmography (PPG) is a non-invasive signal produced by light absorption
      variations due to pulsatile blood volume variations. Indices derived from PPG signals have
      been used successfully to characterize cardiovascular state in patients.

      Dicrotic notch height (Dicpleth), representing the relative height of the dicrotic wave
      compared to the maximum peak of the waveform, has been described as the amount of reflected
      wave, dependent of the vascular tone. Reduction in Dicpleth has been shown to be related to
      reduction of vascular tone due to vasodilator drugs such as salbutamol or glyceryl
      Trinitrate.

      Perfusion Index (PI) represents the ratio of the pulsatile light absorption (i.e the amount
      of blood ejected at each systole) on the continuous absorption (corresponding to the
      non-pulsatile vessels, bones and soft tissues). PI has been described as a reliable tool for
      vascular tone assessment and monitoring

      Primary Evaluation Criteria As Dicpleth and PI are both related to vascular tone and are
      easily derived from the PPG signal, Investigators aimed to explore whether the combined
      analysis of Dicpleth and PI variations would allow for early detection of IOH during the
      during a standardized propofol-remifentanil anesthesia induction.

      Estimate the correlations between variations of Dicpleth and MAP, and PI and MAP during
      induction of anaesthesia and during bolus of vasopressors.

      Estimate if a combined analysis of these two parameters enhanced diagnostic performance for
      detecting IOH under actions of vasoactive effect of anaesthetics.

      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 Hemodynamic parameters (heart rate, systolic arterial pressure [SAP],
      mean arterial pressure [MAP] and diastolic arterial pressure [DAP]), and PPG parameters
      (Dicpleth, PI and SpO2) will be retrospectively sampled every minute during induction. All
      monitoring parameters and curves displayed on the monitor will be recorded on a computer with
      ixTrend© software (ixellence, Wildau, Germany). Investigators defined "pre-pressor" values as
      the measures prior to the vasopressor bolus during IOH episodes. "Peak-pressor" values is
      defined as the maximum effects of vasopressor bolus, when the highest MAP is reached. In
      agreement with most studies, IOH is defined as a MAP drop of more than 20% from baseline MAP.

      In patients presenting a hypotensive episode, 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:

      As ABP may vary quickly, especially during induction of anaesthesia, IOH should be detected
      in real time as even a short period of IOH may have deleterious consequences on vital organs.
      The non-invasive combined analysis of Dicpleth and PI variations would allow for early
      detection of IOH during the induction of general anaesthesia.

      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.

      During their interventional neuroradiology procedure, all patients' routine monitoring will
      consist of electrocardiogram, pulsated oxygen saturation, end-tidal CO2, 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).

      In agreement with most studies, IOH is defined as a MAP drop of more than 20% from baseline
      MAP.

      Hemodynamic parameters (heart rate, systolic arterial pressure [SAP], mean arterial pressure
      [MAP] and diastolic arterial pressure [DAP]), and PPG parameters (Dicpleth, PI and SpO2) will
      be retrospectively sampled every minute during induction.

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

      Number of selected subjects The primary aim of the study is to estimate the AUC of the ROC
      curve of both ΔDicpleth and ΔPI to track IOH during induction. Sample size was determined
      with an expected AUC at 0.85, an expected incidence of hypotension of 80% and the width of
      the confidence interval of 1. With a power of 80%, the number of patients to include was then
      62.15 Secondary objective is to evaluate AUC of the ROC curve for combination of ΔDicpleth
      and ΔPI.

      Statistics Changes of the parameters are analysed using Wilcoxon rank test. Correlation tests
      between ΔDicpleth and ΔMAP in one hand, and ΔPI and ΔMAP are performed by using Spearman
      test. Areas under the curve (AUC) of Receiver Operating Characteristic (ROC) curve (with 95%
      confidence interval) of ΔDicpleth and ΔPI to detect IOH episode will be estimated and
      eventually compared using DeLong test. Youden method is used to determine the optimal
      ΔDicpleth and ΔPI cut-off values to detect IOH episodes. Values are expressed as median and
      interquartile range [25th;75th percentiles]. P<0.05 is considered as statistically
      significant. Statistical analysis is performed using Prism 6.00© (Graphpad Software, Inc, La
      Jolla, CA, USA) and R 3.3.0 software (R foundation for Statistical Computing, Vienna,
      Austria).

      Patients who have non-measurable Dicpleth at baseline before induction of anaesthesia will be
      excluded from the analysis
observational model: Other
time perspective: Prospective
measure: Continuous measure of mean arterial pressure (MAP in mmHg)
time frame: Time Frame: duration of the interventional neuroradiology procedure: 1 day
description: We calculated the variation of MAP during the induction period from the relative variations (in percent) from their baseline values. During vasopressor boluses, respective parameter's variations are calculated between "pre-pressor" and "peak-pressor" measurements.
measure: Continuous measure of SpO2 in % by photoplethysmography
time frame: Time Frame: duration of the interventional neuroradiology procedure: 1 day
description: We calculated variations of Dicpleth, and perfusion index (PI) during the induction period from the relative variations (in percent) from their baseline values. During vasopressor boluses, respective parameter's variations are calculated between "pre-pressor" and "peak-pressor" measurements.
intervention type: Procedure
intervention name: All monitoring
description: Dicpleth and PI are obtained a posteriori from the PPG waveform reconstruction and blindly from ABP values. Dicpleth is defined as the ratio of the height of the dicrotic notch (from nadir point of the complex to the notch) to the height of the systolic peak (from nadir point of the complex to the pic), measured at end-expiratory time (average of 3 consecutive complex). PI is calculated as the ratio of the pulsatile component of the PPG signal and the continuous component.
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: Hopital Lariboisière
responsible party type: Principal Investigator
investigator affiliation: Hopital Lariboisière
investigator full name: Joaquim MATEO
investigator title: MD
mesh term: Hypotension
sharing ipd: Undecided