xml: <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/NCT05967403</url>
    </required_header>
    <id_info>
      <org_study_id>EC/05/23/2282</org_study_id>
      <nct_id>NCT05967403</nct_id>
    </id_info>
    <brief_title>Performance Analysis of Hermetic Closed-loop Anesthesia Delivery System</brief_title>
    <official_title>Anaesthesia Depth Consistency and System Performance of a Hermetic Closed-loop Anaesthesia Delivery System: A Randomized Validation Pilot Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sir Ganga Ram Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sir Ganga Ram Hospital</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>
        Total intravenous anaesthesia (TIVA) is now a preferred technique for providing general&#xD;
        anaesthesia (GA) because of its various inherent advantages like reduced postoperative nausea&#xD;
        and vomiting (PONV), improved quality of post-operative recovery, anti-inflammatory and&#xD;
        antioxidant action, anti-neoplastic activity, analgesic action, and absence of greenhouse&#xD;
        effect. The evolution and advancement in automated anaesthesia delivery systems particularly&#xD;
        for propofol have made propofol-TIVA more efficient by removing the human interface for both&#xD;
        rate and concentration adjustments. Automated computer-controlled closed loop anaesthesia&#xD;
        device adjusts propofol delivery based on patient's frontal cortex electrical activity&#xD;
        determined by bispectral index (BIS).&#xD;
  &#xD;
        Closed loop anaesthesia delivery system (CLADS) is an indigenously developed patented (Patent&#xD;
        no.502/DEL/2003 &amp; US 9,108,013 B2) computer-controlled anaesthesia delivery system which&#xD;
        works with feedback loop information elicited by BIS monitoring and delivers propofol TIVA to&#xD;
        the patient via a non-TCI automated infusion pump. It has been an extensively used and&#xD;
        validated in patients undergoing both cardiac and non-cardiac surgical procedures.&#xD;
  &#xD;
        A new compact and upgraded version of CLADS is now available. This new version incorporates&#xD;
        the anesthetic depth monitor, hemodynamic monitor, controller, user interface and actuator&#xD;
        syringe pump into a single, compact and user-friendly module.&#xD;
  &#xD;
        The investigators aim to conduct a prospective randomized pilot study comparing the new CLADS&#xD;
        and older CLADS version with respect to: adequacy of anaesthesia depth maintenance,&#xD;
        performance characteristic of propofol delivery system, propofol requirement, haemodynamics&#xD;
        stability, recovery from anesthesia and postoperative sedation.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Propofol total intravenous anaesthesia (TIVA) is a preferred technique for providing&#xD;
        induction and maintenance of general anaesthesia (GA). As opposed to the conventional inhaled&#xD;
        anesthetics for maintaining GA, propofol TIVA has several advantages, such as, lower&#xD;
        incidence of postoperative nausea and vomiting (PONV), antinociceptive and anti-inflammatory&#xD;
        action, anti-neoplastic activity, and most importantly, its environment disposition (no&#xD;
        greenhouse effect); and therefore, has potential to replace inhaled vapors for GA.&#xD;
  &#xD;
        The introduction of target-controlled infusion (TCI) pumps has allowed precision control in&#xD;
        propofol delivery as compared to the conventional manually operated infusion pumps. In&#xD;
        manually operated infusion pumps the clinician regulates the propofol infusion rate to&#xD;
        achieve the desired anaesthesia depth, whereas TCI-pumps deliver propofol using inbuilt&#xD;
        algorithms based on the pharmacokinetic (PK) and pharmacodynamic (PD) profile of propofol.&#xD;
        Two of the most used PK-PD models for propofol delivery are the Marsh model and the Schneider&#xD;
        model. Whereas in the Marsh model the user can set the desired target plasma concentration,&#xD;
        Schneider model allows the user to set the desired target effect site concentration for&#xD;
        achieving adequate depth of GA.&#xD;
  &#xD;
        Over the last two decades the evolution and advancement in automated anaesthesia delivery&#xD;
        systems, particularly for propofol administration, has made propofol-TIVA delivery more&#xD;
        efficient by removing the human interface required for adjusting real-time propofol delivery,&#xD;
        both rate and concentration of propofol. Automated anaesthesia delivery systems deliver&#xD;
        propofol based on ascertaining frontal cortex electrical activity as determined by the&#xD;
        processed electroencephalogram, the bispectral index (BIS) score. These devices regulate&#xD;
        propofol delivery based on a feedback loop involving the BIS score (control variable)&#xD;
        generated by the patient and the propofol infusion pump (actuator) and attempts to keep the&#xD;
        values within a pre-assigned range, consistent with robust GA depth.&#xD;
  &#xD;
        Closed loop anaesthesia delivery system (CLADS) is an indigenously developed patented (Patent&#xD;
        no.502/DEL/2003 &amp; US 9,108,013 B2) computer-controlled anaesthesia delivery system which&#xD;
        works with feedback loop information elicited by BIS monitoring and delivers propofol TIVA to&#xD;
        the patient via a non-TCI automated infusion pump. The basic control algorithm is based on&#xD;
        the relationship between the infusion rates of propofol and BIS values, taking into&#xD;
        consideration the pharmacokinetic variables, such as, drug distribution and clearance. The&#xD;
        system updates the EEG data every 5-seconds and calculates the BIS error, a difference&#xD;
        between the target BIS and the actual BIS value using the proportional-integral-derivative&#xD;
        (PID) controller. During anaesthesia induction the target concentration is achieved in a&#xD;
        stepwise manner with BIS feedback received every 5-seconds. During maintenance phase of&#xD;
        anaesthesia, the propofol delivery is modified every 1-epoch of 30-seconds duration. In each&#xD;
        epoch an average of initial 3-BIS values (of every 5-seconds) and average of last 3-BIS&#xD;
        values (of every 5-seconds) are compared, and a trend assessment is made. If the trend&#xD;
        indicates increasing BIS values, then higher propofol rate is delivered by the infusion pump&#xD;
        (actuator) and vice-versa. The control algorithm is implemented using a personal computer&#xD;
        (PC) with a Pentium 4 processor. The PC controls communication with the infusion pump&#xD;
        (Pilot-C, Fresenius, Paris, France) and the vital sign monitor (AS5, Datex Ohmeda Division,&#xD;
        GE Healthcare, Singapore) through RS 232 serial ports.&#xD;
  &#xD;
        CLADS has been extensively used and validated for administering propofol TIVA in patients&#xD;
        undergoing both cardiac and non-cardiac surgical procedures. In a multi-centric study on&#xD;
        evaluation of anaesthesia delivery by CLADS, it was shown that CLADS maintains depth of&#xD;
        anaesthesia with far more precision as compared to manual administration.&#xD;
  &#xD;
        A new compact and upgraded version of CLADS (Clarity Medical Private Ltd., Mohali, Punjab&#xD;
        Indiais now available. The new version integrates the anaesthetic depth as well as the&#xD;
        hemodynamic monitor, the controller, the user interface and the actuator syringe pump into a&#xD;
        single, compact and user-friendly module.&#xD;
  &#xD;
        The investigators aim to conduct a prospective randomised pilot to compare the multiple&#xD;
        connected-unit conventional CLADS with the hermetically unit-integrated CLADS version, with&#xD;
        respect to, the adequacy of anaesthesia depth (primary objective); and, performance&#xD;
        characteristic, propofol requirement, haemodynamic stability, recovery from anaesthesia and&#xD;
        postoperative sedation of the delivery systems (secondary objectives).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 20, 2023</start_date>
    <completion_date type="Anticipated">November 2024</completion_date>
    <primary_completion_date type="Anticipated">October 2024</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>
      <intervention_model_description>One hundred participants (50/group) aged 18-65 years, ASA physical status I-II, of either sex, and undergoing elective non-cardiac surgery of minimum 60-minutes duration recruitment will be randomly divided into one of the two groups:&#xD;
  Group-1 [Conventional CLADS (CC) group, n= 50]: Anaesthesia will be induced and maintained with propofol administered using the automated conventional CLADS.&#xD;
  Group-2 [Hermetic CLADS (HC) group, n= 50]: Anaesthesia will be induced and maintained with propofol administered using the hermetic CLADS.</intervention_model_description>
      <primary_purpose>Other</primary_purpose>
      <masking>Double (Participant, Outcomes Assessor)</masking>
      <masking_description>Inside the operating, the attending anaesthesiologist will not be blinded to the technique utilized to administer general anaesthesia (GA) and the recovery parameters immediately after extubation. However, the postoperative patient recovery profile will be evaluated by an independent assessor blinded to the GA technique and peri-extubation profile.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Anaesthesia depth consistency</measure>
      <time_frame>From beginning of anaesthesia till 5- minutes post skin closure</time_frame>
      <description>It will be determined by the percentage of the anaesthesia time during which the BIS remained +/- 10 of the target BIS of 50</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Performance characteristic of propofol delivery system</measure>
      <time_frame>From beginning of anaesthesia till 5- minutes post skin closure</time_frame>
      <description>It will be determined using the Varvel criteria parameter :median performance error (MDPE). This parameter is calculated by the computer software which analyses the intraoperative BIS data. This parameter have no unit of measurement. It's just an abstract number. Higher the value means worse performance of propofol delivery system. It is not a scale.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Performance characteristic of propofol delivery system</measure>
      <time_frame>From start of anesthesia till 5- minutes post skin closure</time_frame>
      <description>It will be determined using the Varvel criteria parameter: median absolute performance error (MDAPE).This parameter is calculated by the computer software which analyses the intraoperative BIS data. This parameter have no unit of measurement. Its just a abstract number.Higher the value means worse performance of propofol delivery system. It is not a scale.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Performance characteristic of propofol delivery system</measure>
      <time_frame>From start of anesthesia till 5- minutes post skin closure</time_frame>
      <description>It will be determined using the Varvel criteria parameter: wobble. This parameter is calculated by the computer software which analyses the intraoperative BIS data. This parameter have no unit of measurement. Its just a abstract number.Higher the value means worse performance of propofol delivery system. It is not a scale.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Performance characteristic of propofol delivery system</measure>
      <time_frame>From start of anesthesia till 5- minutes post skin closure</time_frame>
      <description>It will be determined using the Varvel criteria parameter: global score. It is calculated using the formula Median absolute performance error + wobble / percentage of the anesthesia time during which the BIS remained +/- 10 of the target BIS of 50. This parameter have no unit of measurement. Its just a abstract number.Higher the value means worse performance of propofol delivery system. It is not a scale.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>. Propofol induction dose (mg/kg)</measure>
      <time_frame>From start of propofol injection till 10-minutes intraoperatively</time_frame>
      <description>Dose of propofol required for induction of anaesthesia</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>. Propofol maintenance dose (mg/kg/h)</measure>
      <time_frame>From start of propofol injection till 5-minutes post skin closure</time_frame>
      <description>Dose of propofol required for maintenance of anaesthesia</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to loss of consciousness (measured in minutes)</measure>
      <time_frame>From start of propofol injection till 10-minutes intraoperatively</time_frame>
      <description>The time taken (in minutes) from starting propofol induction using CLADS till loss of verbal response.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to induction of anaesthesia (measured in minutes)</measure>
      <time_frame>From start of propofol injection till 10-minutes intraoperatively</time_frame>
      <description>The time taken (in minutes) from starting propofol induction using CLADS till a target BIS value of '50' is achieved</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intra-operative heart Rate (beats per minute)</measure>
      <time_frame>From beginning of anaesthesia till 10 hours intraoperatively]</time_frame>
      <description>Comparison of intra-operative heart rate between the study arms will be done</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intra-operative systolic , diastolic, and mean blood pressure (mmHg)</measure>
      <time_frame>From beginning of anaesthesia till 10 hours intraoperatively]</time_frame>
      <description>Comparison of intra-operative blood pressure- systolic, diastolic, and mean blood pressure between the study arms will be done</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Early recovery from anaesthesia (measured in minutes)</measure>
      <time_frame>From end of anaesthesia till 20-minutes postoperatively</time_frame>
      <description>Time taken by the patient to open his/her eyes after discontinuation of anaesthesia will be noted</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Early recovery from anaesthesia (measured in minutes)</measure>
      <time_frame>From end of anaesthesia till 20-minutes postoperatively</time_frame>
      <description>Time taken for tracheal extubation after discontinuation of anaesthesia will be noted</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Postoperative sedation</measure>
      <time_frame>From end of anaesthesia till 24-hours postoperatively</time_frame>
      <description>Will be assessed using Modified Observer's assessment of alertness/sedation scale. The scale has a maximum value of '5', which refers to a fully awake patient and a minimum value of '0' which refers to a deeply sedated patient.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Anesthesia</condition>
    <arm_group>
      <arm_group_label>Conventional CLADS group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the conventional (prototype) closed-loop anaesthesia delivery system (CLADS). A BIS value of 50 will be used as the target point for induction and maintenance of anesthesia</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Hermetic CLADS group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the hermetic closed-loop anaesthesia delivery system (CLADS).[(Clarity Medical Private Ltd., Mohali, Punjab India]. A BIS value of 50 will be used as the target point for induction and maintenance of anesthesia</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Propofol</intervention_name>
      <description>Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the conventional closed loop anaesthesia delivery system (CLADS). A BIS value of 50 will be used as the target point for induction and maintenance of anaesthesia.</description>
      <arm_group_label>Conventional CLADS group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Propofol</intervention_name>
      <description>Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the hermetic closed loop anaesthesia delivery system (CLADS). A BIS value of 50 will be used as the target point for induction and maintenance of anaesthesia.</description>
      <arm_group_label>Hermetic CLADS group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  aged 18-65 years-&#xD;
  &#xD;
            -  ASA physical status I-II&#xD;
  &#xD;
            -  undergoing elective non-cardiac surgery of minimum 60-minutes duration&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Uncompensated cardiovascular disease (e.g., uncontrolled hypertension, atrio-&#xD;
               ventricular block, sinus bradycardia, congenital heart disease, reduced LV compliance,&#xD;
               diastolic dysfunction).&#xD;
  &#xD;
            -  Hepato-renal insufficiency.&#xD;
  &#xD;
            -  Any history of neurological disorder (e.g., epilepsy) or brain trauma&#xD;
  &#xD;
            -  Uncontrolled endocrine diseases (e.g., diabetes mellitus, hypothyroidism).&#xD;
  &#xD;
            -  Known allergy/hypersensitivity to the study drug.&#xD;
  &#xD;
            -  History of any psychiatric disorder and/or drug dependence/substance abuse.&#xD;
  &#xD;
            -  Requirement of postoperative ventilation.&#xD;
  &#xD;
            -  Refusal to informed consent.&#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>Nitin Sethi, DNB</last_name>
      <role>Study Director</role>
      <affiliation>Sir Ganga Ram Hospital, New Delhi, INDIA</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Amitabh Dutta, MD, PGDHR</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sir Ganga Ram Hospital, New Delhi, INDIA</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Goverdhan D Puri, MD, PhD</last_name>
      <role>Study Chair</role>
      <affiliation>Post Graduate Institute of Medical Education &amp; Research, Chandigarh, India</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Amitabh Dutta, MD, PGDHR</last_name>
      <phone>+919810848064</phone>
      <email>duttaamitabh@yahoo.co.in</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Nitin Sethi, DNB</last_name>
      <phone>+919717494498</phone>
      <email>nitinsethi77@yahoo.co.in</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Nitin Sethi</name>
        <address>
          <city>New Delhi</city>
          <state>Delhi</state>
          <zip>110060</zip>
          <country>India</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>India</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 21, 2023</study_first_submitted>
    <study_first_submitted_qc>July 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 29, 2023</last_update_submitted>
    <last_update_submitted_qc>July 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Sir Ganga Ram Hospital</investigator_affiliation>
      <investigator_full_name>Nitin Sethi, DNB</investigator_full_name>
      <investigator_title>Senior Consultant, Institute of Anaesthesiology, Pain &amp; Perioperative Medicine</investigator_title>
    </responsible_party>
    <keyword>propofol</keyword>
    <keyword>closed-loop</keyword>
    <keyword>anesthesia</keyword>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <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>
  
  
text: 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/NCT05967403
  org study id: EC/05/23/2282
  nct id: NCT05967403
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Total intravenous anaesthesia (TIVA) is now a preferred technique for providing general
        anaesthesia (GA) because of its various inherent advantages like reduced postoperative nausea
        and vomiting (PONV), improved quality of post-operative recovery, anti-inflammatory and
        antioxidant action, anti-neoplastic activity, analgesic action, and absence of greenhouse
        effect. The evolution and advancement in automated anaesthesia delivery systems particularly
        for propofol have made propofol-TIVA more efficient by removing the human interface for both
        rate and concentration adjustments. Automated computer-controlled closed loop anaesthesia
        device adjusts propofol delivery based on patient's frontal cortex electrical activity
        determined by bispectral index (BIS).
  
        Closed loop anaesthesia delivery system (CLADS) is an indigenously developed patented (Patent
        no.502/DEL/2003 & US 9,108,013 B2) computer-controlled anaesthesia delivery system which
        works with feedback loop information elicited by BIS monitoring and delivers propofol TIVA to
        the patient via a non-TCI automated infusion pump. It has been an extensively used and
        validated in patients undergoing both cardiac and non-cardiac surgical procedures.
  
        A new compact and upgraded version of CLADS is now available. This new version incorporates
        the anesthetic depth monitor, hemodynamic monitor, controller, user interface and actuator
        syringe pump into a single, compact and user-friendly module.
  
        The investigators aim to conduct a prospective randomized pilot study comparing the new CLADS
        and older CLADS version with respect to: adequacy of anaesthesia depth maintenance,
        performance characteristic of propofol delivery system, propofol requirement, haemodynamics
        stability, recovery from anesthesia and postoperative sedation.
  Propofol total intravenous anaesthesia (TIVA) is a preferred technique for providing
        induction and maintenance of general anaesthesia (GA). As opposed to the conventional inhaled
        anesthetics for maintaining GA, propofol TIVA has several advantages, such as, lower
        incidence of postoperative nausea and vomiting (PONV), antinociceptive and anti-inflammatory
        action, anti-neoplastic activity, and most importantly, its environment disposition (no
        greenhouse effect); and therefore, has potential to replace inhaled vapors for GA.
  
        The introduction of target-controlled infusion (TCI) pumps has allowed precision control in
        propofol delivery as compared to the conventional manually operated infusion pumps. In
        manually operated infusion pumps the clinician regulates the propofol infusion rate to
        achieve the desired anaesthesia depth, whereas TCI-pumps deliver propofol using inbuilt
        algorithms based on the pharmacokinetic (PK) and pharmacodynamic (PD) profile of propofol.
        Two of the most used PK-PD models for propofol delivery are the Marsh model and the Schneider
        model. Whereas in the Marsh model the user can set the desired target plasma concentration,
        Schneider model allows the user to set the desired target effect site concentration for
        achieving adequate depth of GA.
  
        Over the last two decades the evolution and advancement in automated anaesthesia delivery
        systems, particularly for propofol administration, has made propofol-TIVA delivery more
        efficient by removing the human interface required for adjusting real-time propofol delivery,
        both rate and concentration of propofol. Automated anaesthesia delivery systems deliver
        propofol based on ascertaining frontal cortex electrical activity as determined by the
        processed electroencephalogram, the bispectral index (BIS) score. These devices regulate
        propofol delivery based on a feedback loop involving the BIS score (control variable)
        generated by the patient and the propofol infusion pump (actuator) and attempts to keep the
        values within a pre-assigned range, consistent with robust GA depth.
  
        Closed loop anaesthesia delivery system (CLADS) is an indigenously developed patented (Patent
        no.502/DEL/2003 & US 9,108,013 B2) computer-controlled anaesthesia delivery system which
        works with feedback loop information elicited by BIS monitoring and delivers propofol TIVA to
        the patient via a non-TCI automated infusion pump. The basic control algorithm is based on
        the relationship between the infusion rates of propofol and BIS values, taking into
        consideration the pharmacokinetic variables, such as, drug distribution and clearance. The
        system updates the EEG data every 5-seconds and calculates the BIS error, a difference
        between the target BIS and the actual BIS value using the proportional-integral-derivative
        (PID) controller. During anaesthesia induction the target concentration is achieved in a
        stepwise manner with BIS feedback received every 5-seconds. During maintenance phase of
        anaesthesia, the propofol delivery is modified every 1-epoch of 30-seconds duration. In each
        epoch an average of initial 3-BIS values (of every 5-seconds) and average of last 3-BIS
        values (of every 5-seconds) are compared, and a trend assessment is made. If the trend
        indicates increasing BIS values, then higher propofol rate is delivered by the infusion pump
        (actuator) and vice-versa. The control algorithm is implemented using a personal computer
        (PC) with a Pentium 4 processor. The PC controls communication with the infusion pump
        (Pilot-C, Fresenius, Paris, France) and the vital sign monitor (AS5, Datex Ohmeda Division,
        GE Healthcare, Singapore) through RS 232 serial ports.
  
        CLADS has been extensively used and validated for administering propofol TIVA in patients
        undergoing both cardiac and non-cardiac surgical procedures. In a multi-centric study on
        evaluation of anaesthesia delivery by CLADS, it was shown that CLADS maintains depth of
        anaesthesia with far more precision as compared to manual administration.
  
        A new compact and upgraded version of CLADS (Clarity Medical Private Ltd., Mohali, Punjab
        Indiais now available. The new version integrates the anaesthetic depth as well as the
        hemodynamic monitor, the controller, the user interface and the actuator syringe pump into a
        single, compact and user-friendly module.
  
        The investigators aim to conduct a prospective randomised pilot to compare the multiple
        connected-unit conventional CLADS with the hermetically unit-integrated CLADS version, with
        respect to, the adequacy of anaesthesia depth (primary objective); and, performance
        characteristic, propofol requirement, haemodynamic stability, recovery from anaesthesia and
        postoperative sedation of the delivery systems (secondary objectives).
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: One hundred participants (50/group) aged 18-65 years, ASA physical status I-II, of either sex, and undergoing elective non-cardiac surgery of minimum 60-minutes duration recruitment will be randomly divided into one of the two groups:
  Group-1 [Conventional CLADS (CC) group, n= 50]: Anaesthesia will be induced and maintained with propofol administered using the automated conventional CLADS.
  Group-2 [Hermetic CLADS (HC) group, n= 50]: Anaesthesia will be induced and maintained with propofol administered using the hermetic CLADS.
  primary purpose: Other
  masking: Double (Participant, Outcomes Assessor)
  masking description: Inside the operating, the attending anaesthesiologist will not be blinded to the technique utilized to administer general anaesthesia (GA) and the recovery parameters immediately after extubation. However, the postoperative patient recovery profile will be evaluated by an independent assessor blinded to the GA technique and peri-extubation profile.
  measure: Anaesthesia depth consistency
  time frame: From beginning of anaesthesia till 5- minutes post skin closure
  description: It will be determined by the percentage of the anaesthesia time during which the BIS remained +/- 10 of the target BIS of 50
  measure: Performance characteristic of propofol delivery system
  time frame: From beginning of anaesthesia till 5- minutes post skin closure
  description: It will be determined using the Varvel criteria parameter :median performance error (MDPE). This parameter is calculated by the computer software which analyses the intraoperative BIS data. This parameter have no unit of measurement. It's just an abstract number. Higher the value means worse performance of propofol delivery system. It is not a scale.
  measure: Performance characteristic of propofol delivery system
  time frame: From start of anesthesia till 5- minutes post skin closure
  description: It will be determined using the Varvel criteria parameter: median absolute performance error (MDAPE).This parameter is calculated by the computer software which analyses the intraoperative BIS data. This parameter have no unit of measurement. Its just a abstract number.Higher the value means worse performance of propofol delivery system. It is not a scale.
  measure: Performance characteristic of propofol delivery system
  time frame: From start of anesthesia till 5- minutes post skin closure
  description: It will be determined using the Varvel criteria parameter: wobble. This parameter is calculated by the computer software which analyses the intraoperative BIS data. This parameter have no unit of measurement. Its just a abstract number.Higher the value means worse performance of propofol delivery system. It is not a scale.
  measure: Performance characteristic of propofol delivery system
  time frame: From start of anesthesia till 5- minutes post skin closure
  description: It will be determined using the Varvel criteria parameter: global score. It is calculated using the formula Median absolute performance error + wobble / percentage of the anesthesia time during which the BIS remained +/- 10 of the target BIS of 50. This parameter have no unit of measurement. Its just a abstract number.Higher the value means worse performance of propofol delivery system. It is not a scale.
  measure: . Propofol induction dose (mg/kg)
  time frame: From start of propofol injection till 10-minutes intraoperatively
  description: Dose of propofol required for induction of anaesthesia
  measure: . Propofol maintenance dose (mg/kg/h)
  time frame: From start of propofol injection till 5-minutes post skin closure
  description: Dose of propofol required for maintenance of anaesthesia
  measure: Time to loss of consciousness (measured in minutes)
  time frame: From start of propofol injection till 10-minutes intraoperatively
  description: The time taken (in minutes) from starting propofol induction using CLADS till loss of verbal response.
  measure: Time to induction of anaesthesia (measured in minutes)
  time frame: From start of propofol injection till 10-minutes intraoperatively
  description: The time taken (in minutes) from starting propofol induction using CLADS till a target BIS value of '50' is achieved
  measure: Intra-operative heart Rate (beats per minute)
  time frame: From beginning of anaesthesia till 10 hours intraoperatively]
  description: Comparison of intra-operative heart rate between the study arms will be done
  measure: Intra-operative systolic , diastolic, and mean blood pressure (mmHg)
  time frame: From beginning of anaesthesia till 10 hours intraoperatively]
  description: Comparison of intra-operative blood pressure- systolic, diastolic, and mean blood pressure between the study arms will be done
  measure: Early recovery from anaesthesia (measured in minutes)
  time frame: From end of anaesthesia till 20-minutes postoperatively
  description: Time taken by the patient to open his/her eyes after discontinuation of anaesthesia will be noted
  measure: Early recovery from anaesthesia (measured in minutes)
  time frame: From end of anaesthesia till 20-minutes postoperatively
  description: Time taken for tracheal extubation after discontinuation of anaesthesia will be noted
  measure: Postoperative sedation
  time frame: From end of anaesthesia till 24-hours postoperatively
  description: Will be assessed using Modified Observer's assessment of alertness/sedation scale. The scale has a maximum value of '5', which refers to a fully awake patient and a minimum value of '0' which refers to a deeply sedated patient.
  arm group label: Conventional CLADS group
  arm group type: Active Comparator
  description: Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the conventional (prototype) closed-loop anaesthesia delivery system (CLADS). A BIS value of 50 will be used as the target point for induction and maintenance of anesthesia
  arm group label: Hermetic CLADS group
  arm group type: Active Comparator
  description: Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the hermetic closed-loop anaesthesia delivery system (CLADS).[(Clarity Medical Private Ltd., Mohali, Punjab India]. A BIS value of 50 will be used as the target point for induction and maintenance of anesthesia
  intervention type: Drug
  intervention name: Propofol
  description: Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the conventional closed loop anaesthesia delivery system (CLADS). A BIS value of 50 will be used as the target point for induction and maintenance of anaesthesia.
  arm group label: Conventional CLADS group
  intervention type: Drug
  intervention name: Propofol
  description: Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the hermetic closed loop anaesthesia delivery system (CLADS). A BIS value of 50 will be used as the target point for induction and maintenance of anaesthesia.
  arm group label: Hermetic CLADS group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Nitin Sethi, DNB
  role: Study Director
  affiliation: Sir Ganga Ram Hospital, New Delhi, INDIA
  last name: Amitabh Dutta, MD, PGDHR
  role: Principal Investigator
  affiliation: Sir Ganga Ram Hospital, New Delhi, INDIA
  last name: Goverdhan D Puri, MD, PhD
  role: Study Chair
  affiliation: Post Graduate Institute of Medical Education & Research, Chandigarh, India
  last name: Amitabh Dutta, MD, PGDHR
  phone: +919810848064
  email: duttaamitabh@yahoo.co.in
  last name: Nitin Sethi, DNB
  phone: +919717494498
  email: nitinsethi77@yahoo.co.in
  facility: 
  country: India
  responsible party type: Principal Investigator
  investigator affiliation: Sir Ganga Ram Hospital
  investigator full name: Nitin Sethi, DNB
  investigator title: Senior Consultant, Institute of Anaesthesiology, Pain & Perioperative Medicine
  mesh term: Propofol
  sharing ipd: No