<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/NCT03307551</url>
  </required_header>
  <id_info>
    <org_study_id>EC/09/17/1254</org_study_id>
    <nct_id>NCT03307551</nct_id>
  </id_info>
  <brief_title>Evaluation of Automated Propofol Delivery in Patients Undergoing Thoracic Surgery</brief_title>
  <official_title>Evaluation of Automated Delivery of Propofol Using Closed-Loop Anaesthesia Delivery System in Patients Undergoing Thoracic Surgery: A Randomised Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr Nitin Sethi</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Automated delivery of propofol using computer-controlled closed loop anaesthesia device&#xD;
      delivers propofol based on patient's frontal cortex electrical activity as determined by&#xD;
      bi-spectral index (BIS). Evaluation of anaesthesia delivery by these systems has shown that&#xD;
      they deliver propofol and maintain depth of anaesthesia with far more precision as compared&#xD;
      to manual administration.&#xD;
&#xD;
      By automatically controlling anaesthesia depth consistency they provide time to the&#xD;
      anaesthesiologist to focus on other aspects of patient care such as managing intra-operative&#xD;
      hemodynamics and ventilation perturbations during major surgeries.&#xD;
&#xD;
      Closed loop anaesthesia delivery system (CLADS) is an indigenously developed continuous&#xD;
      automated intravenous infusion system which delivers propofol based on patients EEG profile&#xD;
      (BIS) feedback. Although a few studies have already evaluated these automated systems in&#xD;
      patients undergoing thoracic surgery, but suffered from significant limitations (small number&#xD;
      of patients, not dedicated to thoracic surgery cohort). Currently, there is no data available&#xD;
      regarding CLADS performance vis a vis adequacy of GA and haemodynamic profile in patients&#xD;
      undergoing thoracic surgery.&#xD;
&#xD;
      We contend that propofol as delivered by CLADS will proffer greater consistency to&#xD;
      anaesthesia depth, intra-operative hemodynamic stability, and rapid recovery upon anaesthesia&#xD;
      discontinuation than manual means of delivering propofol TIVA. This randomised controlled&#xD;
      study aims to compare the efficiency of CLADS-driven propofol TIVA versus manually controlled&#xD;
      propofol TIVA in patients undergoing thoracic surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After Ethics Committee approval and written informed consent, thirty-participants (30 per&#xD;
      group) aged 18-65 years, ASA physical status I-III, of either sex, and undergoing unilateral&#xD;
      open thoracic surgery or unilateral video-assisted thoracic surgery (VATS) will be included&#xD;
      in this single centre (Sir Ganga Ram Hospital, New Delhi-110060, India) prospective,&#xD;
      single-blinded, two-arm, randomised controlled study.&#xD;
&#xD;
      The patients who qualify inclusion criteria and consent for recruitment will be randomly&#xD;
      divided into one of the two groups:&#xD;
&#xD;
      Group-1 [CLADS Group, n=15, Study group]: Anaesthesia will be induced and maintained with&#xD;
      propofol administered using the automated CLADS.&#xD;
&#xD;
      Group-2 [Manual Group, n=15, Control group]: Anaesthesia will be induced and maintained with&#xD;
      propofol administered using manually controlled infusion pumps titrated to BIS scores.&#xD;
&#xD;
      Sample-size Estimation In a previous multi-centre study, the percentage of time the BIS was&#xD;
      within 10 percentage of the target BIS was 81.4 percent in the CLADS group versus 55.34&#xD;
      percent in the manual group. Based on the above, to detect 20 percent difference in the two&#xD;
      groups, a sample size of 12 patients per group to provide 90 percent power with a bilateral&#xD;
      alpha risk value of 0.05 will be required. We plan to recruit a total of 30 patients to cover&#xD;
      up for unanticipated losses after the recruitment.&#xD;
&#xD;
      Randomisation, Allocation Concealment The patients will be randomly allocated to one of the&#xD;
      two groups based on a computer-generated random number table. Randomisation sequence&#xD;
      concealment will include opaque-sealed envelopes with alphabetic codes whose distribution&#xD;
      will be in control of an independent analyst. The envelopes will be opened; patient's&#xD;
      data-slip will be pasted on them, and will be sent back to the control analyst.&#xD;
&#xD;
      Blinding Strategy Inside the OR, the attending anaesthesiologist will not be blinded to the&#xD;
      technique utilised to administer GA and the recovery parameters immediately after extubation.&#xD;
      However, the postoperative patient recovery profile will be evaluated by an independent&#xD;
      assessor blinded to the GA technique and periextubation profile.&#xD;
&#xD;
      Management of Anesthesia Two peripheral venous lines (18G/20G catheter) will be secured.&#xD;
      Invasive vascular access (arterial line for direct continuous blood pressure assessment,&#xD;
      central venous catheter) will be secured as per the requirement of surgery. Standard&#xD;
      monitoring (EKG, NIBP, pulse oximeter, EtCO2) will be applied. A BIS sensor (Covidien IIc,&#xD;
      Mansfield, USA) will be applied over the patient's forehead according to manufacturer's&#xD;
      instructions (Model DSC-XP, Aspect medical system, USA) prior to induction of anaesthesia for&#xD;
      continuous monitoring of depth-of-anaesthesia.&#xD;
&#xD;
      Anaesthesia Technique&#xD;
&#xD;
      All the patients will receive pre-induction fentanyl-citrate 2 mcg/kg and anesthesia will be&#xD;
      induced with propofol. In the CLADS group, propofol administration rate will be controlled by&#xD;
      a feedback loop facilitated by BIS monitoring. A BIS value of 50 will be used as the target&#xD;
      point for induction and maintenance of anesthesia. The Manual group would comprise manual&#xD;
      propofol administration by an intravenous infusion pump to maintain a target BIS of 50 during&#xD;
      induction and maintenance of anesthesia.&#xD;
&#xD;
      After induction of anesthesia, atracurium besylate 0.05mg/kg will be given to facilitate&#xD;
      tracheal intubation. In order to facilitate one lung ventilation (OLV) patients trachea will&#xD;
      be intubated using appropriate-sized double-lumen tube in all the patients. Oxygen-air&#xD;
      mixture (FiO2 0.50) will be used for intraoperative ventilation in both the groups. In&#xD;
      addition, starting the period after tracheal intubation, all the patients will receive 1&#xD;
      mcg/kg/hr fentanyl infusion for intraoperative analgesia. Intraoperative muscle relaxation&#xD;
      will be maintained using atracurium infusion controlled by train-of-four response on&#xD;
      peripheral neuromuscular monitor (Infinity TridentNMT Smartpod, Draeger Medical Systems, Inc&#xD;
      Telford, USA).&#xD;
&#xD;
      In all patients undergoing open thoracic surgery, a thoracic epidural catheter will be placed&#xD;
      in the indicated intervertebral space for facilitating postoperative analgesia.&#xD;
&#xD;
      Thirty minutes before the end of surgery, non-opioid analgesics, such as paracetamol 1-gm,&#xD;
      tramadol 100 mg and/or diclofenac 75 mg will be administered to all the patients. Propofol&#xD;
      delivery will be stopped at the point of completion of skin closure. Residual neuromuscular&#xD;
      blockade (assessed with train-of-four response) will be reversed with neostigmine (50 µg/kg)&#xD;
      and glycopyrrolate (20 µg/kg). Tracheal extubation will be undertaken if planned&#xD;
      post-extubation ventilation is not instituted and the patients are wide awake and obeying&#xD;
      commands.&#xD;
&#xD;
      Assessment Parameters Intraoperative&#xD;
&#xD;
        1. Adequacy of anaesthesia depth will be determined by the percentage of the valid CLADS&#xD;
           time during which the BIS remained within 10% of the target BIS (50), median absolute&#xD;
           performance error (MDAPE), wobble and global score (Varvel criteria)&#xD;
&#xD;
        2. Haemodynamic parameters such a heart rate, non-invasive blood pressure will be recorded&#xD;
&#xD;
        3. Early recovery from anaesthesia profile which includes time to eye opening and time to&#xD;
           extubation after discontinuation of anesthesia will be noted&#xD;
&#xD;
      Postoperative&#xD;
&#xD;
        1. Sedation will be assessed using Modified Observer's assessment of alertness/sedation&#xD;
           scale.&#xD;
&#xD;
        2. Incidence of awareness will be determined using Modified Brice Questionnaire.&#xD;
&#xD;
      After discontinuation of anaesthesia delivery (0-time point) the time to eye opening and time&#xD;
      to extubation will be determined. After tracheal extubation, the patients will be shifted to&#xD;
      postoperative recovery room adjoining OT suites and will be closely observed for oxygenation&#xD;
      and ventilation status, pain (numeric rating score) and sedation. Patients with epidural&#xD;
      catheter in-situ will be started with PCEA pump for pain relief. Patients will be analysed&#xD;
      for intra-operative awareness using Modified Brice Questionnaire (24 hours, 48 hours&#xD;
      postoperatively).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 31, 2017</start_date>
  <completion_date type="Actual">June 25, 2019</completion_date>
  <primary_completion_date type="Actual">June 25, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>30-patients aged 18-65 years, ASA physical status I-III, of either sex, and undergoing unilateral open thoracic surgery or unilateral video-assisted thoracic surgery (VATS) will randomly allocated by computer generated numbers to one of the following two groups of 15 patients each:&#xD;
Group-1 [CLADS Group, n=15, Study group]: Anaesthesia will be induced and maintained with propofol administered using the automated CLADS.&#xD;
Group-2 [Manual Group, n=15, Control group]: Anaesthesia will be induced and maintained with propofol administered using manually controlled infusion pumps titrated to BIS scores.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>The patient will be blinded to the type of anaesthesia intervention.The attending anaesthesiologist will however not be blinded to the technique utilized to administer GA and recovery immediately after extubation inside the OR. The postoperative patient recovery profile will be evaluated by an independent assessor blinded to the technique of GA.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Anaesthesia depth consistency using BIS scores</measure>
    <time_frame>From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively</time_frame>
    <description>Determined by the percentage of the total anaesthesia time in which the BIS scores remain within a score of 10% of the target BIS (i.e. BIS-50) in both the study arms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Performance Characteristic of propofol anaesthesia delivery system</measure>
    <time_frame>From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively</time_frame>
    <description>Determined by using Varvel criteria parameters; median performance error (MDP), median absolute performance error (MDAPE), wobble and global score in both the study arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Intra-operative heart Rate (beats per minute)</measure>
    <time_frame>From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively</time_frame>
    <description>Comparison of intra-operative heart rate between both the arms will be done</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Intra-operative systolic , diastolic, and mean (mmHg)</measure>
    <time_frame>From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively</time_frame>
    <description>Comparison of intra-operative blood pressure- systolic, diastolic, and mean between both the arms will be done</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recovery from anesthesia</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>Recovery from anesthesia</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>Intra-operative awareness</measure>
    <time_frame>From the end of anaesthesia till 48-hours postoperatively</time_frame>
    <description>Will be assessed using modified brice questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Propofol induction dose (mg)</measure>
    <time_frame>From start of propofol injection till 2- minutes intraoperatively</time_frame>
    <description>Dose of propofol required for induction of anaesthesia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Propofol maintenance dose (mg/kg/hr)</measure>
    <time_frame>From 2-minutes intraoperatively till 10-hours intraoperatively</time_frame>
    <description>Dose of propofol required for maintenance of anaesthesia</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Thoracic Diseases</condition>
  <condition>Surgery</condition>
  <arm_group>
    <arm_group_label>CLADS group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Anaesthesia will be induced and maintained with Propofol administered by CLADS. Its administration rate will be controlled by a feedback loop facilitated by BIS monitoring. A BIS value of 50 will be used as the target point for induction and maintenance of anaesthesia.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Manual group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Anaesthesia will be induced and maintained with propofol administration by an intravenous infusion pump. Its administration rate will be controlled manually to maintain a target BIS of 50 during induction and maintenance of anaesthesia.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>Propofol delivery will be controlled using automated closed loop anaesthesia delivery system which will control propofol delivery rate to consistent anaesthetic depth (BIS-50) feedback from the patient (CLADS group)</description>
    <arm_group_label>CLADS group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>Propofol delivery will be controlled using infusion pumps which will be manually controlled to deliver propofol to maintain consistent anaesthetic depth (BIS-50). (Manual group)</description>
    <arm_group_label>Manual group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ASA physical status I-III&#xD;
&#xD;
          -  undergoing unilateral open thoracic surgery or unilateral video-assisted thoracic&#xD;
             surgery (VATS) Exclusion Criteria:&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncompensated cardiovascular disease (e.g. uncontrolled hypertension,&#xD;
             atrio-ventricular block, sinus bradycardia, congenital heart disease, reduced LV&#xD;
             compliance, diastolic dysfunction)&#xD;
&#xD;
          -  Hepato-renal insufficiency&#xD;
&#xD;
          -  Uncontrolled endocrinology disease (e.g. diabetes mellitus, hypothyroidism)&#xD;
&#xD;
          -  Known allergy/hypersensitivity to the study drug&#xD;
&#xD;
          -  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>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_official>
    <last_name>Jayashree Sood, MD,FFRCA</last_name>
    <role>Study Director</role>
    <affiliation>Sir Ganga Ram Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sir Ganga Ram Hospital</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>June 2019</verification_date>
  <study_first_submitted>October 6, 2017</study_first_submitted>
  <study_first_submitted_qc>October 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>June 29, 2019</last_update_submitted>
  <last_update_submitted_qc>June 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Sir Ganga Ram Hospital</investigator_affiliation>
    <investigator_full_name>Dr Nitin Sethi</investigator_full_name>
    <investigator_title>Associate Professor &amp; Consultant</investigator_title>
  </responsible_party>
  <keyword>propofol, automated, manual</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thoracic Diseases</mesh_term>
  </condition_browse>
  <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>


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/NCT03307551
org study id: EC/09/17/1254
nct id: NCT03307551
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Automated delivery of propofol using computer-controlled closed loop anaesthesia device
      delivers propofol based on patient's frontal cortex electrical activity as determined by
      bi-spectral index (BIS). Evaluation of anaesthesia delivery by these systems has shown that
      they deliver propofol and maintain depth of anaesthesia with far more precision as compared
      to manual administration.

      By automatically controlling anaesthesia depth consistency they provide time to the
      anaesthesiologist to focus on other aspects of patient care such as managing intra-operative
      hemodynamics and ventilation perturbations during major surgeries.

      Closed loop anaesthesia delivery system (CLADS) is an indigenously developed continuous
      automated intravenous infusion system which delivers propofol based on patients EEG profile
      (BIS) feedback. Although a few studies have already evaluated these automated systems in
      patients undergoing thoracic surgery, but suffered from significant limitations (small number
      of patients, not dedicated to thoracic surgery cohort). Currently, there is no data available
      regarding CLADS performance vis a vis adequacy of GA and haemodynamic profile in patients
      undergoing thoracic surgery.

      We contend that propofol as delivered by CLADS will proffer greater consistency to
      anaesthesia depth, intra-operative hemodynamic stability, and rapid recovery upon anaesthesia
      discontinuation than manual means of delivering propofol TIVA. This randomised controlled
      study aims to compare the efficiency of CLADS-driven propofol TIVA versus manually controlled
      propofol TIVA in patients undergoing thoracic surgery.
After Ethics Committee approval and written informed consent, thirty-participants (30 per
      group) aged 18-65 years, ASA physical status I-III, of either sex, and undergoing unilateral
      open thoracic surgery or unilateral video-assisted thoracic surgery (VATS) will be included
      in this single centre (Sir Ganga Ram Hospital, New Delhi-110060, India) prospective,
      single-blinded, two-arm, randomised controlled study.

      The patients who qualify inclusion criteria and consent for recruitment will be randomly
      divided into one of the two groups:

      Group-1 [CLADS Group, n=15, Study group]: Anaesthesia will be induced and maintained with
      propofol administered using the automated CLADS.

      Group-2 [Manual Group, n=15, Control group]: Anaesthesia will be induced and maintained with
      propofol administered using manually controlled infusion pumps titrated to BIS scores.

      Sample-size Estimation In a previous multi-centre study, the percentage of time the BIS was
      within 10 percentage of the target BIS was 81.4 percent in the CLADS group versus 55.34
      percent in the manual group. Based on the above, to detect 20 percent difference in the two
      groups, a sample size of 12 patients per group to provide 90 percent power with a bilateral
      alpha risk value of 0.05 will be required. We plan to recruit a total of 30 patients to cover
      up for unanticipated losses after the recruitment.

      Randomisation, Allocation Concealment The patients will be randomly allocated to one of the
      two groups based on a computer-generated random number table. Randomisation sequence
      concealment will include opaque-sealed envelopes with alphabetic codes whose distribution
      will be in control of an independent analyst. The envelopes will be opened; patient's
      data-slip will be pasted on them, and will be sent back to the control analyst.

      Blinding Strategy Inside the OR, the attending anaesthesiologist will not be blinded to the
      technique utilised to administer 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 periextubation profile.

      Management of Anesthesia Two peripheral venous lines (18G/20G catheter) will be secured.
      Invasive vascular access (arterial line for direct continuous blood pressure assessment,
      central venous catheter) will be secured as per the requirement of surgery. Standard
      monitoring (EKG, NIBP, pulse oximeter, EtCO2) will be applied. A BIS sensor (Covidien IIc,
      Mansfield, USA) will be applied over the patient's forehead according to manufacturer's
      instructions (Model DSC-XP, Aspect medical system, USA) prior to induction of anaesthesia for
      continuous monitoring of depth-of-anaesthesia.

      Anaesthesia Technique

      All the patients will receive pre-induction fentanyl-citrate 2 mcg/kg and anesthesia will be
      induced with propofol. In the CLADS group, propofol administration rate will be controlled by
      a feedback loop facilitated by BIS monitoring. A BIS value of 50 will be used as the target
      point for induction and maintenance of anesthesia. The Manual group would comprise manual
      propofol administration by an intravenous infusion pump to maintain a target BIS of 50 during
      induction and maintenance of anesthesia.

      After induction of anesthesia, atracurium besylate 0.05mg/kg will be given to facilitate
      tracheal intubation. In order to facilitate one lung ventilation (OLV) patients trachea will
      be intubated using appropriate-sized double-lumen tube in all the patients. Oxygen-air
      mixture (FiO2 0.50) will be used for intraoperative ventilation in both the groups. In
      addition, starting the period after tracheal intubation, all the patients will receive 1
      mcg/kg/hr fentanyl infusion for intraoperative analgesia. Intraoperative muscle relaxation
      will be maintained using atracurium infusion controlled by train-of-four response on
      peripheral neuromuscular monitor (Infinity TridentNMT Smartpod, Draeger Medical Systems, Inc
      Telford, USA).

      In all patients undergoing open thoracic surgery, a thoracic epidural catheter will be placed
      in the indicated intervertebral space for facilitating postoperative analgesia.

      Thirty minutes before the end of surgery, non-opioid analgesics, such as paracetamol 1-gm,
      tramadol 100 mg and/or diclofenac 75 mg will be administered to all the patients. Propofol
      delivery will be stopped at the point of completion of skin closure. Residual neuromuscular
      blockade (assessed with train-of-four response) will be reversed with neostigmine (50 µg/kg)
      and glycopyrrolate (20 µg/kg). Tracheal extubation will be undertaken if planned
      post-extubation ventilation is not instituted and the patients are wide awake and obeying
      commands.

      Assessment Parameters Intraoperative

        1. Adequacy of anaesthesia depth will be determined by the percentage of the valid CLADS
           time during which the BIS remained within 10% of the target BIS (50), median absolute
           performance error (MDAPE), wobble and global score (Varvel criteria)

        2. Haemodynamic parameters such a heart rate, non-invasive blood pressure will be recorded

        3. Early recovery from anaesthesia profile which includes time to eye opening and time to
           extubation after discontinuation of anesthesia will be noted

      Postoperative

        1. Sedation will be assessed using Modified Observer's assessment of alertness/sedation
           scale.

        2. Incidence of awareness will be determined using Modified Brice Questionnaire.

      After discontinuation of anaesthesia delivery (0-time point) the time to eye opening and time
      to extubation will be determined. After tracheal extubation, the patients will be shifted to
      postoperative recovery room adjoining OT suites and will be closely observed for oxygenation
      and ventilation status, pain (numeric rating score) and sedation. Patients with epidural
      catheter in-situ will be started with PCEA pump for pain relief. Patients will be analysed
      for intra-operative awareness using Modified Brice Questionnaire (24 hours, 48 hours
      postoperatively).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 30-patients aged 18-65 years, ASA physical status I-III, of either sex, and undergoing unilateral open thoracic surgery or unilateral video-assisted thoracic surgery (VATS) will randomly allocated by computer generated numbers to one of the following two groups of 15 patients each:
Group-1 [CLADS Group, n=15, Study group]: Anaesthesia will be induced and maintained with propofol administered using the automated CLADS.
Group-2 [Manual Group, n=15, Control group]: Anaesthesia will be induced and maintained with propofol administered using manually controlled infusion pumps titrated to BIS scores.
primary purpose: Basic Science
masking: Double (Participant, Outcomes Assessor)
masking description: The patient will be blinded to the type of anaesthesia intervention.The attending anaesthesiologist will however not be blinded to the technique utilized to administer GA and recovery immediately after extubation inside the OR. The postoperative patient recovery profile will be evaluated by an independent assessor blinded to the technique of GA.
measure: Anaesthesia depth consistency using BIS scores
time frame: From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
description: Determined by the percentage of the total anaesthesia time in which the BIS scores remain within a score of 10% of the target BIS (i.e. BIS-50) in both the study arms.
measure: Performance Characteristic of propofol anaesthesia delivery system
time frame: From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
description: Determined by using Varvel criteria parameters; median performance error (MDP), median absolute performance error (MDAPE), wobble and global score in both the study arms
measure: Change in Intra-operative heart Rate (beats per minute)
time frame: From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
description: Comparison of intra-operative heart rate between both the arms will be done
measure: Change in Intra-operative systolic , diastolic, and mean (mmHg)
time frame: From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
description: Comparison of intra-operative blood pressure- systolic, diastolic, and mean between both the arms will be done
measure: Recovery from anesthesia
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: Recovery from anesthesia
time frame: From end of anaesthesia till 20-minutes postoperatively]
description: Time taken for tracheal extubation after discontinuation of anaesthesia will be noted
measure: Intra-operative awareness
time frame: From the end of anaesthesia till 48-hours postoperatively
description: Will be assessed using modified brice questionnaire
measure: Propofol induction dose (mg)
time frame: From start of propofol injection till 2- minutes intraoperatively
description: Dose of propofol required for induction of anaesthesia
measure: Propofol maintenance dose (mg/kg/hr)
time frame: From 2-minutes intraoperatively till 10-hours intraoperatively
description: Dose of propofol required for maintenance of anaesthesia
arm group label: CLADS group
arm group type: Active Comparator
description: Anaesthesia will be induced and maintained with Propofol administered by CLADS. Its administration rate will be controlled by a feedback loop facilitated by BIS monitoring. A BIS value of 50 will be used as the target point for induction and maintenance of anaesthesia.
arm group label: Manual group
arm group type: Active Comparator
description: Anaesthesia will be induced and maintained with propofol administration by an intravenous infusion pump. Its administration rate will be controlled manually to maintain a target BIS of 50 during induction and maintenance of anaesthesia.
intervention type: Drug
intervention name: Propofol
description: Propofol delivery will be controlled using automated closed loop anaesthesia delivery system which will control propofol delivery rate to consistent anaesthetic depth (BIS-50) feedback from the patient (CLADS group)
arm group label: CLADS group
intervention type: Drug
intervention name: Propofol
description: Propofol delivery will be controlled using infusion pumps which will be manually controlled to deliver propofol to maintain consistent anaesthetic depth (BIS-50). (Manual group)
arm group label: Manual group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Goverdhan D Puri, MD, PhD
role: Study Chair
affiliation: Post Graduate Institute of Medical Education & Research, Chandigarh, India
last name: Jayashree Sood, MD,FFRCA
role: Study Director
affiliation: Sir Ganga Ram Hospital
facility: 
country: India
responsible party type: Sponsor-Investigator
investigator affiliation: Sir Ganga Ram Hospital
investigator full name: Dr Nitin Sethi
investigator title: Associate Professor & Consultant
mesh term: Thoracic Diseases
mesh term: Propofol
sharing ipd: No