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/NCT06006676</url>
    </required_header>
    <id_info>
      <org_study_id>256932</org_study_id>
      <nct_id>NCT06006676</nct_id>
    </id_info>
    <brief_title>IMV to Accelerate Recovery of Lung Function in Veno-venous Extracorporeal Membrane Oxygenation; Lung Rest Or Moderate Mechanical Ventilation in ECMO</brief_title>
    <acronym>ROMEO</acronym>
    <official_title>Mechanical Ventilation to Accelerate Recovery of Lung Function in Veno-venous Extracorporeal Membrane Oxygenation; Lung Rest Or Moderate Mechanical Ventilation in ECMO: Randomized Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Guy's and St Thomas' NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </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>
        Feasibility trial to inform a future multicentre randomized control trial. The investigators&#xD;
        aim to evaluate the feasibility of a trial of near apnoeic ventilation (two breaths per&#xD;
        minute) compared with standard ventilation (respiratory rate between 10 and 30 breaths) for&#xD;
        patients with acute respiratory distress syndrome (ARDS) supported with veno-venous&#xD;
        extracorporeal membrane oxygenation (V-V ECMO). Additionally, when a patient is determined as&#xD;
        ready to wean from ECMO the investigators will explore the feasibility of two ECMO weaning&#xD;
        strategies and explore the physiological effects on respiratory effort and gas exchange.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background&#xD;
  &#xD;
        Acute respiratory distress syndrome (ARDS) is a common clinical syndrome characterised by&#xD;
        life threatening respiratory failure requiring mechanical ventilation. Although lifesaving,&#xD;
        mechanical ventilation can cause further injury to the lungs, known as ventilator-induced&#xD;
        lung injury (VILI). Strategies to mitigate VILI in ARDS have proven to improve patient&#xD;
        outcomes. ARDS patients that have severe lung failure, despite mechanical ventilation, often&#xD;
        require veno-venous extracorporeal membrane oxygenation (ECMO). ECMO uses an artificial&#xD;
        membrane lung to take over gas exchange. This allows reduction in injurious ventilator&#xD;
        settings thereby also reducing VILI.&#xD;
  &#xD;
        While the indications for ECMO initiation are standardised in the UK and ECMO utilisation is&#xD;
        increasing,there remains uncertainty as to the best approach to mechanical ventilation whilst&#xD;
        patients are receiving ECMO and what strategies are maximally attenuating VILI during its&#xD;
        use. Importantly it is known that despite the reduction in ventilatory pressures and volumes&#xD;
        facilitated by ECMO, these sickest and most fragile lungs continue to be susceptible to VILI.&#xD;
        A reduction in respiratory rate (RR) to near apnoeic ventilation (2 breaths per minute) seems&#xD;
        to be associated with the greatest physiological reduction in VILI components, whilst&#xD;
        maintaining important physiological mechanisms such as surfactant production which rely on&#xD;
        some lung inflation. Employing a near apnoeic ventilation strategy may be associated with&#xD;
        faster resolution of ARDS resulting in reduced duration of ECMO, ventilation and ICU stay,&#xD;
        and healthcare costs.&#xD;
  &#xD;
        Rationale&#xD;
  &#xD;
        Interventions which mitigate VILI lead to less lung inflammation/oedema and better outcomes&#xD;
        in ARDS patients. However, the recent REST trial of extracorporeal carbon dioxide removal&#xD;
        showed that the resultant modest reduction in volume and pressure had no clinical effect.&#xD;
        Hence, a modest reduction in ventilation may not be as effective as an almost complete&#xD;
        absence (near apnoeic) of ventilation. The latter can only be achieved alongside ECMO&#xD;
        support. Reductions in respiratory rate to near apnoeic ventilation have multiple effects on&#xD;
        VILI, including:&#xD;
  &#xD;
          1. Modulation of disease activity through reduced opening and closing of lung units&#xD;
             (atelectrauma);&#xD;
  &#xD;
          2. Reductions in frequency of applied driving pressure and overall intensity of minute&#xD;
             ventilation (barotrauma)&#xD;
  &#xD;
          3. Prevention of overdistension of the aerated lung (volutrauma)&#xD;
  &#xD;
          4. Attenuation of circulating markers of lung injury and inflammation ('biotrauma')&#xD;
  &#xD;
          5. Reduced development of aberrant fibrosis within the lung [9]. Patients on ECMO are prone&#xD;
             to pulmonary fibrosis, for which VILI is known to be major contributor&#xD;
  &#xD;
        Multinational surveys of mechanical ventilation during ECMO support show that 45.7% of&#xD;
        centres used a moderate respiratory rate (10-20 breaths per minute) delivered with ~10-15&#xD;
        cmH2O PEEP and 10-15 cmH2O driving pressure. Evidence shows a 3% increase in the hazard of&#xD;
        death for every 1 cmH2O increase in ventilator driving pressure during ECMO support. Taken&#xD;
        together, international experience and trend show that ventilator mechanical power (a measure&#xD;
        of the energy transmitted to the lung) is a major determinant of VILI and is only modestly&#xD;
        decreased by the currently employed moderate ventilation strategies which mainly reduce the&#xD;
        driving pressure applied per breath. Mechanical power is, however, significantly reduced by&#xD;
        lower respiratory rates. Near apnoeic ventilation during ECMO is clinically feasible with gas&#xD;
        exchange and oxygen delivery being maintained by ECMO.&#xD;
  &#xD;
        The ROMEO trial&#xD;
  &#xD;
        The investigators have conducted a detailed search of PubMed, Ovid, Cochrane databases,&#xD;
        Google Scholar and the WHO International Clinical Trials Registry Platform. To-date, no large&#xD;
        prospective studies have or are addressing the use of near apnoeic ventilation during ECMO.&#xD;
        Consequently, a multicentre randomised open label study of near apnoea ventilation versus&#xD;
        standard of care is planned. This future multicentre trial will be powered for patient&#xD;
        centred outcomes (e.g., time to ECMO decannulation and mortality) together with a trial cost&#xD;
        utility analysis at 12 months.&#xD;
  &#xD;
        To demonstrate the feasibility of our trial design, we will conduct a 50 patient feasibility&#xD;
        study at Guy's and St Thomas' NHS Foundation Trust. This will evaluate the feasibility of the&#xD;
        intervention (ability to recruit; ability to deliver the ventilator strategy; ability to&#xD;
        deliver the ECMO weaning strategies), the physiological changes induced by near apnoea&#xD;
        ventilation together with the impact on plasma and broncho-alveolar lavage biomarkers and&#xD;
        collect exploratory data on clinical outcomes.&#xD;
  &#xD;
        As there is a paucity of evidence regarding predictors of ECMO weaning success, we will&#xD;
        evaluate comprehensive physiological data obtained during each weaning trial attempt to&#xD;
        evaluate the patient-ventilator-membrane lung interactions.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">October 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2025</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>Parallel group randomised prospective open label trial of two ventilation strategies during V-V ECMO for ARDS with standardised crossover weaning studies</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of patients receiving a ventilation strategy other than the assigned ventilation strategy over the 72 hour period following randomisation</measure>
      <time_frame>During the 72 hours following randomisation</time_frame>
      <description>Number of patients receiving a ventilation strategy other than the assigned ventilation strategy over the 72 hour period following randomisation (excluding time off the ICU for imaging or surgical/interventional procedures)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Time to achieving carbon dioxide output (VCO2) natural lung &gt; 50% of total of CO2 output</measure>
      <time_frame>Up to 6 months following date of randomisation</time_frame>
      <description>Time to achieving carbon dioxide output (VCO2) natural lung &gt; 50% of total of VCO2 (VCO2 from ECMO plus VCO2 from natural lung)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to achieve a PaO2 &gt; 30 kPa with Cilley's test (arterial oxygenation achieved after an increase in FiO2 to 1.0 with no other changes to the ventilator or ECMO settings)</measure>
      <time_frame>Up to 6 months following date of randomisation</time_frame>
      <description>Time to achieve a PaO2 &gt; 30 kPa with Cilley's test (arterial oxygenation achieved after an increase in FiO2 to 1.0 with no other changes to the ventilator or ECMO settings)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of successful ECMO weaning trial</measure>
      <time_frame>Up to 6 months following date of randomisation</time_frame>
      <description>Proportion of ECMO weaning trials which result in success (sweep gas flow of 0 for 1 hour without: respiratory rate &gt;35, P0.1 measured by ventilator less than -10cmH2O, oxygen saturations &lt;88%, pH &lt;7.35 due to increasing PaCO2, obvious clinical distress)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of patients with non-adherence to assigned ECMO weaning strategy</measure>
      <time_frame>Up to 6 months following date of randomisation</time_frame>
      <description>Number of patients in whom there is non-adherence to the assigned ECMO weaning strategy (for example, clinicians make a decision to decannulate despite the outcome of a weaning trial)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in total compliance of the respiratory system during a low flow pressure volume loop after 72hrs of the assigned ventilation strategy</measure>
      <time_frame>72 hours</time_frame>
      <description>Difference between 72 hour and baseline total compliance of the respiratory system (compliance of the whole pressure volume loop curve obtained with 8L/s flow, pressure from 5 to 40cmH2O with volume limit of 12mls/kg ideal body weight</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Time from randomisation to ECMO decannulation</measure>
      <time_frame>Up to 6 months following date of randomisation</time_frame>
      <description>Time from randomisation to ECMO decannulation</description>
    </other_outcome>
    <other_outcome>
      <measure>Rate of decannulation from ECMO</measure>
      <time_frame>Up to 6 months following date of randomisation</time_frame>
      <description>Rate of decannulation from ECMO</description>
    </other_outcome>
    <other_outcome>
      <measure>Time to achieve a successful ECMO weaning trial</measure>
      <time_frame>Up to 6 months following date of randomisation</time_frame>
      <description>Time to achieve a successful ECMO weaning trial</description>
    </other_outcome>
    <other_outcome>
      <measure>Duration of invasive mechanical ventilation and total ventilator days (excluding high-flow nasal cannulae)</measure>
      <time_frame>Up to 6 months following date of randomisation</time_frame>
      <description>Duration of invasive mechanical ventilation and total ventilator days (excluding high-flow nasal cannulae)</description>
    </other_outcome>
    <other_outcome>
      <measure>Length of stay in the ECMO centre</measure>
      <time_frame>Up to 6 months following date of randomisation</time_frame>
      <description>Length of stay in the ECMO centre</description>
    </other_outcome>
    <other_outcome>
      <measure>ECMO mortality</measure>
      <time_frame>Up to 6 months following date of randomisation</time_frame>
      <description>Mortality at the ECMO centre</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in oxygen saturations during a weaning trial</measure>
      <time_frame>Up to 6 months following date of randomisation</time_frame>
      <description>Difference between baseline and end of trial value of oxygen saturations derived from pulse oximetry</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in oesophageal pressure swing during a weaning trial</measure>
      <time_frame>Up to 6 months following randomisation</time_frame>
      <description>Difference between baseline and end of trial value of oesophageal pressure swing</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in ventilatory efficiency during a weaning trial</measure>
      <time_frame>Up to 6 months following randomisation</time_frame>
      <description>Difference between baseline and end of trial value of ventilatory efficiency, calculated as the minute ventilation (measured by mechanical ventilator) divided by the CO2 clearance by the natural lung (measured using volumetric capnography)</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in modified Borg Dyspnoea Score during a weaning trial</measure>
      <time_frame>Up to 6 months following randomisation</time_frame>
      <description>Difference between baseline and end of trial modified Borg dyspnoea score</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in haematocrit during a weaning trial</measure>
      <time_frame>Up to 6 months following randomisation</time_frame>
      <description>Difference between baseline and end of trial haematocrit measured on an arterial blood gase</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>ARDS</condition>
    <arm_group>
      <arm_group_label>Near Apnoeic Ventilation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Near Apnoeic ventilation (with a respiratory rate of 2 breaths per minute, plateau pressure of 30cmH20 and PEEP set according to the mean airway pressure being delivered during mechanical ventilation prior to randomisation) for a 72 hour period following randomisation</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Standard Care</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Standard care for patient on ECMO as per consultant with respiratory rate of 15-30, PEEP of 10cmH20 or more and Plateau pressure of 25cmH20 or less for a 72 hour period following randomisation</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Near Apnoeic ventilation</intervention_name>
      <description>Near Apnoeic ventilation (with a respiratory rate of 2 breaths per minute, plateau pressure of 30cmH20 and PEEP set according to the mean airway pressure being delivered during mechanical ventilation prior to randomisation) for a 72 hour period following randomisation</description>
      <arm_group_label>Near Apnoeic Ventilation</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Crossover standardised ECMO weaning trials</intervention_name>
      <description>When all patients are eligible for a trial of ECMO weaning, they will have standardised ECMO weaning trials lasting up to 1 hour with 0 sweep gas flow. 1) &quot;One-stage weaning&quot;- sweep gas flow rate sequentially decreased to zero 2) &quot;Two-stage weaning&quot;- fraction of oxygen of sweep gas flow decreased to 0.21 sequentially. Then the sweep gas flow rate decreased to 0 sequentially</description>
      <arm_group_label>Near Apnoeic Ventilation</arm_group_label>
      <arm_group_label>Standard Care</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion criteria&#xD;
  &#xD;
            -  Adult patients aged 18 years or older on the date of screening&#xD;
  &#xD;
            -  Acute and potentially reversible cause of ARDS&#xD;
  &#xD;
            -  Receiving invasive mechanical ventilation&#xD;
  &#xD;
            -  Requiring ECMO for severe ARDS&#xD;
  &#xD;
            -  Tidal volume ≥ 2.5ml/kg predicted body weight&#xD;
  &#xD;
          Exclusion criteria:&#xD;
  &#xD;
          Patients who meet the one or more of the following will be excluded from the trial.&#xD;
  &#xD;
            -  Declined consent&#xD;
  &#xD;
            -  &gt;12 hours following ECMO initiation&#xD;
  &#xD;
            -  Patient likely to die or for withdrawal of life sustaining therapies within 24 hours&#xD;
  &#xD;
            -  Use of V-A ECMO or hybrid ECMO modes&#xD;
  &#xD;
            -  Current pregnancy&#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>Luigi Camporota, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Guy's and St Thomas' NHS Foundation Trust</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Luigi Camporota, MD, PhD</last_name>
      <phone>02071883036</phone>
      <email>luigi.camporota@gstt.nhs.uk</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Gill Radcliffe</last_name>
      <phone>02071888070</phone>
      <email>gill.radcliffe@gstt.nhs.uk</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Guys &amp; St. Thomas' NHS Foundation Trust</name>
        <address>
          <city>London</city>
          <zip>SE1 7EH</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>October 6, 2021</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 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>
    <keyword>ARDS</keyword>
    <keyword>Critical Care</keyword>
    <keyword>ECMO</keyword>
    <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/NCT06006676
  org study id: 256932
  nct id: NCT06006676
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Feasibility trial to inform a future multicentre randomized control trial. The investigators
        aim to evaluate the feasibility of a trial of near apnoeic ventilation (two breaths per
        minute) compared with standard ventilation (respiratory rate between 10 and 30 breaths) for
        patients with acute respiratory distress syndrome (ARDS) supported with veno-venous
        extracorporeal membrane oxygenation (V-V ECMO). Additionally, when a patient is determined as
        ready to wean from ECMO the investigators will explore the feasibility of two ECMO weaning
        strategies and explore the physiological effects on respiratory effort and gas exchange.
  Background
  
        Acute respiratory distress syndrome (ARDS) is a common clinical syndrome characterised by
        life threatening respiratory failure requiring mechanical ventilation. Although lifesaving,
        mechanical ventilation can cause further injury to the lungs, known as ventilator-induced
        lung injury (VILI). Strategies to mitigate VILI in ARDS have proven to improve patient
        outcomes. ARDS patients that have severe lung failure, despite mechanical ventilation, often
        require veno-venous extracorporeal membrane oxygenation (ECMO). ECMO uses an artificial
        membrane lung to take over gas exchange. This allows reduction in injurious ventilator
        settings thereby also reducing VILI.
  
        While the indications for ECMO initiation are standardised in the UK and ECMO utilisation is
        increasing,there remains uncertainty as to the best approach to mechanical ventilation whilst
        patients are receiving ECMO and what strategies are maximally attenuating VILI during its
        use. Importantly it is known that despite the reduction in ventilatory pressures and volumes
        facilitated by ECMO, these sickest and most fragile lungs continue to be susceptible to VILI.
        A reduction in respiratory rate (RR) to near apnoeic ventilation (2 breaths per minute) seems
        to be associated with the greatest physiological reduction in VILI components, whilst
        maintaining important physiological mechanisms such as surfactant production which rely on
        some lung inflation. Employing a near apnoeic ventilation strategy may be associated with
        faster resolution of ARDS resulting in reduced duration of ECMO, ventilation and ICU stay,
        and healthcare costs.
  
        Rationale
  
        Interventions which mitigate VILI lead to less lung inflammation/oedema and better outcomes
        in ARDS patients. However, the recent REST trial of extracorporeal carbon dioxide removal
        showed that the resultant modest reduction in volume and pressure had no clinical effect.
        Hence, a modest reduction in ventilation may not be as effective as an almost complete
        absence (near apnoeic) of ventilation. The latter can only be achieved alongside ECMO
        support. Reductions in respiratory rate to near apnoeic ventilation have multiple effects on
        VILI, including:
  
          1. Modulation of disease activity through reduced opening and closing of lung units
             (atelectrauma);
  
          2. Reductions in frequency of applied driving pressure and overall intensity of minute
             ventilation (barotrauma)
  
          3. Prevention of overdistension of the aerated lung (volutrauma)
  
          4. Attenuation of circulating markers of lung injury and inflammation ('biotrauma')
  
          5. Reduced development of aberrant fibrosis within the lung [9]. Patients on ECMO are prone
             to pulmonary fibrosis, for which VILI is known to be major contributor
  
        Multinational surveys of mechanical ventilation during ECMO support show that 45.7% of
        centres used a moderate respiratory rate (10-20 breaths per minute) delivered with ~10-15
        cmH2O PEEP and 10-15 cmH2O driving pressure. Evidence shows a 3% increase in the hazard of
        death for every 1 cmH2O increase in ventilator driving pressure during ECMO support. Taken
        together, international experience and trend show that ventilator mechanical power (a measure
        of the energy transmitted to the lung) is a major determinant of VILI and is only modestly
        decreased by the currently employed moderate ventilation strategies which mainly reduce the
        driving pressure applied per breath. Mechanical power is, however, significantly reduced by
        lower respiratory rates. Near apnoeic ventilation during ECMO is clinically feasible with gas
        exchange and oxygen delivery being maintained by ECMO.
  
        The ROMEO trial
  
        The investigators have conducted a detailed search of PubMed, Ovid, Cochrane databases,
        Google Scholar and the WHO International Clinical Trials Registry Platform. To-date, no large
        prospective studies have or are addressing the use of near apnoeic ventilation during ECMO.
        Consequently, a multicentre randomised open label study of near apnoea ventilation versus
        standard of care is planned. This future multicentre trial will be powered for patient
        centred outcomes (e.g., time to ECMO decannulation and mortality) together with a trial cost
        utility analysis at 12 months.
  
        To demonstrate the feasibility of our trial design, we will conduct a 50 patient feasibility
        study at Guy's and St Thomas' NHS Foundation Trust. This will evaluate the feasibility of the
        intervention (ability to recruit; ability to deliver the ventilator strategy; ability to
        deliver the ECMO weaning strategies), the physiological changes induced by near apnoea
        ventilation together with the impact on plasma and broncho-alveolar lavage biomarkers and
        collect exploratory data on clinical outcomes.
  
        As there is a paucity of evidence regarding predictors of ECMO weaning success, we will
        evaluate comprehensive physiological data obtained during each weaning trial attempt to
        evaluate the patient-ventilator-membrane lung interactions.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Parallel group randomised prospective open label trial of two ventilation strategies during V-V ECMO for ARDS with standardised crossover weaning studies
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Number of patients receiving a ventilation strategy other than the assigned ventilation strategy over the 72 hour period following randomisation
  time frame: During the 72 hours following randomisation
  description: Number of patients receiving a ventilation strategy other than the assigned ventilation strategy over the 72 hour period following randomisation (excluding time off the ICU for imaging or surgical/interventional procedures)
  measure: Time to achieving carbon dioxide output (VCO2) natural lung > 50% of total of CO2 output
  time frame: Up to 6 months following date of randomisation
  description: Time to achieving carbon dioxide output (VCO2) natural lung > 50% of total of VCO2 (VCO2 from ECMO plus VCO2 from natural lung)
  measure: Time to achieve a PaO2 > 30 kPa with Cilley's test (arterial oxygenation achieved after an increase in FiO2 to 1.0 with no other changes to the ventilator or ECMO settings)
  time frame: Up to 6 months following date of randomisation
  description: Time to achieve a PaO2 > 30 kPa with Cilley's test (arterial oxygenation achieved after an increase in FiO2 to 1.0 with no other changes to the ventilator or ECMO settings)
  measure: Rate of successful ECMO weaning trial
  time frame: Up to 6 months following date of randomisation
  description: Proportion of ECMO weaning trials which result in success (sweep gas flow of 0 for 1 hour without: respiratory rate >35, P0.1 measured by ventilator less than -10cmH2O, oxygen saturations <88%, pH <7.35 due to increasing PaCO2, obvious clinical distress)
  measure: Number of patients with non-adherence to assigned ECMO weaning strategy
  time frame: Up to 6 months following date of randomisation
  description: Number of patients in whom there is non-adherence to the assigned ECMO weaning strategy (for example, clinicians make a decision to decannulate despite the outcome of a weaning trial)
  measure: Change in total compliance of the respiratory system during a low flow pressure volume loop after 72hrs of the assigned ventilation strategy
  time frame: 72 hours
  description: Difference between 72 hour and baseline total compliance of the respiratory system (compliance of the whole pressure volume loop curve obtained with 8L/s flow, pressure from 5 to 40cmH2O with volume limit of 12mls/kg ideal body weight
  measure: Time from randomisation to ECMO decannulation
  time frame: Up to 6 months following date of randomisation
  description: Time from randomisation to ECMO decannulation
  measure: Rate of decannulation from ECMO
  time frame: Up to 6 months following date of randomisation
  description: Rate of decannulation from ECMO
  measure: Time to achieve a successful ECMO weaning trial
  time frame: Up to 6 months following date of randomisation
  description: Time to achieve a successful ECMO weaning trial
  measure: Duration of invasive mechanical ventilation and total ventilator days (excluding high-flow nasal cannulae)
  time frame: Up to 6 months following date of randomisation
  description: Duration of invasive mechanical ventilation and total ventilator days (excluding high-flow nasal cannulae)
  measure: Length of stay in the ECMO centre
  time frame: Up to 6 months following date of randomisation
  description: Length of stay in the ECMO centre
  measure: ECMO mortality
  time frame: Up to 6 months following date of randomisation
  description: Mortality at the ECMO centre
  measure: Change in oxygen saturations during a weaning trial
  time frame: Up to 6 months following date of randomisation
  description: Difference between baseline and end of trial value of oxygen saturations derived from pulse oximetry
  measure: Change in oesophageal pressure swing during a weaning trial
  time frame: Up to 6 months following randomisation
  description: Difference between baseline and end of trial value of oesophageal pressure swing
  measure: Change in ventilatory efficiency during a weaning trial
  time frame: Up to 6 months following randomisation
  description: Difference between baseline and end of trial value of ventilatory efficiency, calculated as the minute ventilation (measured by mechanical ventilator) divided by the CO2 clearance by the natural lung (measured using volumetric capnography)
  measure: Change in modified Borg Dyspnoea Score during a weaning trial
  time frame: Up to 6 months following randomisation
  description: Difference between baseline and end of trial modified Borg dyspnoea score
  measure: Change in haematocrit during a weaning trial
  time frame: Up to 6 months following randomisation
  description: Difference between baseline and end of trial haematocrit measured on an arterial blood gase
  arm group label: Near Apnoeic Ventilation
  arm group type: Experimental
  description: Near Apnoeic ventilation (with a respiratory rate of 2 breaths per minute, plateau pressure of 30cmH20 and PEEP set according to the mean airway pressure being delivered during mechanical ventilation prior to randomisation) for a 72 hour period following randomisation
  arm group label: Standard Care
  arm group type: Active Comparator
  description: Standard care for patient on ECMO as per consultant with respiratory rate of 15-30, PEEP of 10cmH20 or more and Plateau pressure of 25cmH20 or less for a 72 hour period following randomisation
  intervention type: Other
  intervention name: Near Apnoeic ventilation
  description: Near Apnoeic ventilation (with a respiratory rate of 2 breaths per minute, plateau pressure of 30cmH20 and PEEP set according to the mean airway pressure being delivered during mechanical ventilation prior to randomisation) for a 72 hour period following randomisation
  arm group label: Near Apnoeic Ventilation
  intervention type: Other
  intervention name: Crossover standardised ECMO weaning trials
  description: When all patients are eligible for a trial of ECMO weaning, they will have standardised ECMO weaning trials lasting up to 1 hour with 0 sweep gas flow. 1) "One-stage weaning"- sweep gas flow rate sequentially decreased to zero 2) "Two-stage weaning"- fraction of oxygen of sweep gas flow decreased to 0.21 sequentially. Then the sweep gas flow rate decreased to 0 sequentially
  arm group label: Near Apnoeic Ventilation
  arm group label: Standard Care
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Luigi Camporota, MD, PhD
  role: Principal Investigator
  affiliation: Guy's and St Thomas' NHS Foundation Trust
  last name: Luigi Camporota, MD, PhD
  phone: 02071883036
  email: luigi.camporota@gstt.nhs.uk
  last name: Gill Radcliffe
  phone: 02071888070
  email: gill.radcliffe@gstt.nhs.uk
  facility: 
  country: United Kingdom
  responsible party type: Sponsor
  sharing ipd: No