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/NCT06014138</url>
    </required_header>
    <id_info>
      <org_study_id>SMRG_318537</org_study_id>
      <nct_id>NCT06014138</nct_id>
    </id_info>
    <brief_title>Volatile Sedation for Patients With the Acute Respiratory Distress Syndrome</brief_title>
    <acronym>ISO-DRIVE</acronym>
    <official_title>Effect of Volatile Sedation on Spontaneous Breathing During Mechanical Ventilation for Patients With the Acute Respiratory Distress Syndrome</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Guy's and St Thomas' NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Sedana Medical</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Guy's and St Thomas' NHS Foundation Trust</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>
        This study will investigate how different types of routine sedation may affect patient's&#xD;
        breathing whilst on a ventilator in the Intensive Care Unit (ICU). There are different&#xD;
        approaches to sedation which may have advantages and disadvantages. During the study patients&#xD;
        will receive both intravenous and inhaled volatile sedation (similar to anaesthetic 'gases'&#xD;
        used for general anaesthesia) and the drive to breath, breathing efforts and function of the&#xD;
        lung will be assessed.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        It is routine for patients to be sedated for their comfort and safety whilst on a ventilator&#xD;
        in the Intensive Care Unit (ICU). Conventionally sedatives are given intravenously, however&#xD;
        inhaled volatile sedation is becoming more popular. Inhaled sedation has recently been&#xD;
        approved by the National Institute for Health and Clinical Excellence (NICE) in the United&#xD;
        Kingdom (UK).&#xD;
  &#xD;
        Whilst being on a ventilator can be life-saving, it can cause potential problems. It is&#xD;
        important that the patient interacts well with the ventilator and that their own breathing&#xD;
        efforts are well regulated. There is evidence that inhaled sedation can specifically help the&#xD;
        lungs when patients have the Acute Respiratory Distress Syndrome (ARDS) and in particular,&#xD;
        inhaled sedation does not appear to suppress patient's own breathing as much as conventional&#xD;
        sedation. Greater spontaneous breathing by the patient is usually positive but needs to be&#xD;
        carefully understood to ensure it is not excessive or damaging to the patient's already&#xD;
        injured lungs.&#xD;
  &#xD;
        This study of 20 patients is designed to carefully measure the impact of inhaled sedation on&#xD;
        the patient's breathing and lung function, in comparison to intravenous sedation.&#xD;
        Measurements will be taken whilst on intravenous sedation before the patient is switched to&#xD;
        an equivalent level of inhaled sedation for six hours, when the measurements will be&#xD;
        repeated. Finally, the patient will go back to their original intravenous sedation and the&#xD;
        measurements taken again. This is called a 'cross-over' study and is a good way to evaluate&#xD;
        the effect of the drug.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 30, 2023</start_date>
    <completion_date type="Anticipated">March 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <phase>Phase 2/Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <intervention_model_description>Prospective, cross-over trial design comparing intravenous versus inhaled volatile sedation</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
      <masking_description>None, open label, physiological study</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Respiratory drive (P0.1)</measure>
      <time_frame>8 hours</time_frame>
      <description>Negative pressure in the first 100milliseconds of inspiration (P0.1) - Physiological parameter</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Respiratory effort (Pmus)</measure>
      <time_frame>8 hours</time_frame>
      <description>End expiratory occlusion pressure (Pmus) - Physiological parameter</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Respiratory effort (PMI)</measure>
      <time_frame>8 hours</time_frame>
      <description>Pressure Muscle Index (PMI) - Physiological parameter</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Respiratory effort (Oesophageal pressure swings)</measure>
      <time_frame>8 hours</time_frame>
      <description>Oesophageal pressure swings - Physiological parameter</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gas exchange (PaO2:FiO2 ratio)</measure>
      <time_frame>8 hours</time_frame>
      <description>Ratio of arterial partial pressure of oxygen to fractional inspired concentration of oxygen (PaO2:FiO2) - Physiological parameter</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gas exchange (pulmonary shunt fraction (Qs/Qt))</measure>
      <time_frame>8 hours</time_frame>
      <description>Pulmonary shunt fraction (Qs/Qt) - Physiological parameter</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gas exchange ( ratio of ventilatory 'dead space' to tidal volume (Vd/Vt))</measure>
      <time_frame>8 hours</time_frame>
      <description>ratio of ventilatory 'dead space' to tidal volume (Vd/Vt) - Physiological parameter</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gas exchange (volume of carbon dioxide breathed out (VCO2))</measure>
      <time_frame>8 hours</time_frame>
      <description>volume of carbon dioxide breathed out (VCO2) - Physiological parameter</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Acute Respiratory Distress Syndrome</condition>
    <condition>Mechanical Ventilation Complication</condition>
    <condition>Sedation Complication</condition>
    <arm_group>
      <arm_group_label>Conventional intravenous sedation</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Conventional intravenous sedation (e.g. propofol) with short acting opioid, titrated to a clinically prescribed sedation score. Period of observation will be 2 hours pre-cross over and 2 hours post cross over.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Inhaled volatile sedation</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Inhaled volatile sedation (Isoflurane) delivered via the AnaConDa device for a 6 hour period (2 hours washout of intravenous sedation / wash-in of volatile to achieve stable baseline, followed by 4 hours of observations at steady state) titrated to an equivalent sedation score. During this period opioid infusion should be maintained at baseline level unless clinical indication for titration of dose.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Propofol</intervention_name>
      <description>Standard care, propofol sedation - 2 hour periods of observation before and after inhaled volatile sedation</description>
      <arm_group_label>Conventional intravenous sedation</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Isoflurane</intervention_name>
      <description>Inhaled volatile sedation for 6 hours - 2 hours wash in / wash out, followed by 4 hours of observations</description>
      <arm_group_label>Inhaled volatile sedation</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Adult patients admitted to the Intensive Care Unit (ICU)&#xD;
  &#xD;
            -  ARDS&#xD;
  &#xD;
            -  Invasive mechanical ventilation (IMV)&#xD;
  &#xD;
            -  Spontaneous breathing in pressures support mode (PSV) for less than or equal to 48&#xD;
               hours&#xD;
  &#xD;
            -  Sedated with intravenous sedation (ie. propofol and / or midazolam and fentanyl or&#xD;
               alternate short acting opioid)&#xD;
  &#xD;
            -  Anticipated to remain on IMV and PSV and with a stable sedation score for a further 24&#xD;
               hours without planned sedation interruption / spontaneous breathing trial or other&#xD;
               significant change in the level of ventilator support&#xD;
  &#xD;
            -  Not receiving / anticipated to receive paralysis&#xD;
  &#xD;
            -  In supine position&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Personal or family history of malignant hyperpyrexia&#xD;
  &#xD;
            -  Known or suspected elevated intracranial pressure&#xD;
  &#xD;
            -  High dose vasopressors (ie. Noradrenaline &gt; 0.3mcg/kg/min or equivalent)&#xD;
  &#xD;
            -  Contra-indication to oesophageal balloon (i.e. oesophageal / upper gastro-intestinal&#xD;
               pathology)&#xD;
  &#xD;
            -  Pregnancy&#xD;
  &#xD;
            -  High dose oral sedatives (e.g. benzodiazepines) or opioids (e.g. oxycodone / oral&#xD;
               morphine) which may affect respiratory drive&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>17 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Guy Glover</last_name>
      <role>Principal Investigator</role>
      <affiliation>Guy's and St Thomas' NHS Trust</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Guy Glover</last_name>
      <phone>00447879696250</phone>
      <email>guy.glover@gstt.nhs.uk</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Gill Radcliffe</last_name>
      <phone>02071887188</phone>
      <email>gillian.radcliffe@gstt.nhs.uk</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Respiratory Distress Syndrome</mesh_term>
      <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
      <mesh_term>Acute Lung Injury</mesh_term>
      <mesh_term>Syndrome</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Propofol</mesh_term>
      <mesh_term>Isoflurane</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/NCT06014138
  org study id: SMRG_318537
  nct id: NCT06014138
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This study will investigate how different types of routine sedation may affect patient's
        breathing whilst on a ventilator in the Intensive Care Unit (ICU). There are different
        approaches to sedation which may have advantages and disadvantages. During the study patients
        will receive both intravenous and inhaled volatile sedation (similar to anaesthetic 'gases'
        used for general anaesthesia) and the drive to breath, breathing efforts and function of the
        lung will be assessed.
  It is routine for patients to be sedated for their comfort and safety whilst on a ventilator
        in the Intensive Care Unit (ICU). Conventionally sedatives are given intravenously, however
        inhaled volatile sedation is becoming more popular. Inhaled sedation has recently been
        approved by the National Institute for Health and Clinical Excellence (NICE) in the United
        Kingdom (UK).
  
        Whilst being on a ventilator can be life-saving, it can cause potential problems. It is
        important that the patient interacts well with the ventilator and that their own breathing
        efforts are well regulated. There is evidence that inhaled sedation can specifically help the
        lungs when patients have the Acute Respiratory Distress Syndrome (ARDS) and in particular,
        inhaled sedation does not appear to suppress patient's own breathing as much as conventional
        sedation. Greater spontaneous breathing by the patient is usually positive but needs to be
        carefully understood to ensure it is not excessive or damaging to the patient's already
        injured lungs.
  
        This study of 20 patients is designed to carefully measure the impact of inhaled sedation on
        the patient's breathing and lung function, in comparison to intravenous sedation.
        Measurements will be taken whilst on intravenous sedation before the patient is switched to
        an equivalent level of inhaled sedation for six hours, when the measurements will be
        repeated. Finally, the patient will go back to their original intravenous sedation and the
        measurements taken again. This is called a 'cross-over' study and is a good way to evaluate
        the effect of the drug.
  allocation: Non-Randomized
  intervention model: Crossover Assignment
  intervention model description: Prospective, cross-over trial design comparing intravenous versus inhaled volatile sedation
  primary purpose: Basic Science
  masking: None (Open Label)
  masking description: None, open label, physiological study
  measure: Respiratory drive (P0.1)
  time frame: 8 hours
  description: Negative pressure in the first 100milliseconds of inspiration (P0.1) - Physiological parameter
  measure: Respiratory effort (Pmus)
  time frame: 8 hours
  description: End expiratory occlusion pressure (Pmus) - Physiological parameter
  measure: Respiratory effort (PMI)
  time frame: 8 hours
  description: Pressure Muscle Index (PMI) - Physiological parameter
  measure: Respiratory effort (Oesophageal pressure swings)
  time frame: 8 hours
  description: Oesophageal pressure swings - Physiological parameter
  measure: Gas exchange (PaO2:FiO2 ratio)
  time frame: 8 hours
  description: Ratio of arterial partial pressure of oxygen to fractional inspired concentration of oxygen (PaO2:FiO2) - Physiological parameter
  measure: Gas exchange (pulmonary shunt fraction (Qs/Qt))
  time frame: 8 hours
  description: Pulmonary shunt fraction (Qs/Qt) - Physiological parameter
  measure: Gas exchange ( ratio of ventilatory 'dead space' to tidal volume (Vd/Vt))
  time frame: 8 hours
  description: ratio of ventilatory 'dead space' to tidal volume (Vd/Vt) - Physiological parameter
  measure: Gas exchange (volume of carbon dioxide breathed out (VCO2))
  time frame: 8 hours
  description: volume of carbon dioxide breathed out (VCO2) - Physiological parameter
  arm group label: Conventional intravenous sedation
  arm group type: Active Comparator
  description: Conventional intravenous sedation (e.g. propofol) with short acting opioid, titrated to a clinically prescribed sedation score. Period of observation will be 2 hours pre-cross over and 2 hours post cross over.
  arm group label: Inhaled volatile sedation
  arm group type: Active Comparator
  description: Inhaled volatile sedation (Isoflurane) delivered via the AnaConDa device for a 6 hour period (2 hours washout of intravenous sedation / wash-in of volatile to achieve stable baseline, followed by 4 hours of observations at steady state) titrated to an equivalent sedation score. During this period opioid infusion should be maintained at baseline level unless clinical indication for titration of dose.
  intervention type: Drug
  intervention name: Propofol
  description: Standard care, propofol sedation - 2 hour periods of observation before and after inhaled volatile sedation
  arm group label: Conventional intravenous sedation
  intervention type: Drug
  intervention name: Isoflurane
  description: Inhaled volatile sedation for 6 hours - 2 hours wash in / wash out, followed by 4 hours of observations
  arm group label: Inhaled volatile sedation
  criteria: 
  gender: All
  minimum age: 17 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Guy Glover
  role: Principal Investigator
  affiliation: Guy's and St Thomas' NHS Trust
  last name: Guy Glover
  phone: 00447879696250
  email: guy.glover@gstt.nhs.uk
  last name: Gill Radcliffe
  phone: 02071887188
  email: gillian.radcliffe@gstt.nhs.uk
  responsible party type: Sponsor
  mesh term: Respiratory Distress Syndrome
  mesh term: Respiratory Distress Syndrome, Newborn
  mesh term: Acute Lung Injury
  mesh term: Syndrome
  mesh term: Propofol
  mesh term: Isoflurane
  sharing ipd: No