<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/NCT01728558</url>
  </required_header>
  <id_info>
    <org_study_id>ANZIC-RC/YS003</org_study_id>
    <nct_id>NCT01728558</nct_id>
  </id_info>
  <brief_title>Early Goal-Directed Sedation Compared With Standard Care in Mechanically Ventilated Critically Ill Patients</brief_title>
  <acronym>SPICE III RCT</acronym>
  <official_title>Early Goal-Directed Sedation Compared With Standard Care in Mechanically Ventilated Critically Ill Patients: a Prospective Multicentre Randomised Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Australian and New Zealand Intensive Care Research Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Health and Medical Research Council, Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Australian and New Zealand Intensive Care Research Centre</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The Use of sedative drugs in intensive care is widespread. A cohort study conducted in&#xD;
      Australia and New Zealand in 2010 revealed a high prevalence of deep sedation within the&#xD;
      first 48 hours of mechanical ventilation which was independently linked to prolonged&#xD;
      ventilation, hospital and 180 days mortality. Clinical practice is moving towards the use of&#xD;
      lighter levels of sedation. Recent RCTs in Europe (JAMA 2012) and previous RCTs (JAMA 2009)&#xD;
      supports growing evidence that dexmedetomidine facilitates rousable sedation, shortens&#xD;
      ventilation time and attenuates delirium when compared to midazolam and propofol.&#xD;
&#xD;
      The investigators confirmed in a pilot study the feasibility, efficacy and safety of a&#xD;
      process of care known as Early Goal Directed Sedation (EGDS) that delivers:&#xD;
&#xD;
        1. Early randomization after intubation or arrival in the ICU (intubated).&#xD;
&#xD;
        2. Early Adequate analgesia after randomization.&#xD;
&#xD;
        3. Goal directed sedation titrated to achieve light sedation.&#xD;
&#xD;
        4. Dexmedetomidine based algorithm as the primary sedative agent with avoidance of&#xD;
           benzodiazepines.&#xD;
&#xD;
      The aim of this study is to assess the effectiveness of Early Goal Directed Sedation when&#xD;
      compared to standard care sedation in critically ill patients.&#xD;
&#xD;
      The study hypothesis is that Early Goal-Directed Sedation (EGDS), compared to standard care&#xD;
      sedation, reduces 90-day all-cause mortality in critically ill patients who require&#xD;
      mechanical ventilation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a large-scale study into the effectiveness of a novel approach for sedation in&#xD;
      ventilated critically ill patients. The primary aim of this study is to determine whether&#xD;
      Early Goal Directed Sedation therapy, compared to standard care sedation, reduces 90-day&#xD;
      mortality in critically ill patients ventilated &gt; 24 hrs.&#xD;
&#xD;
      The study will be a randomized, unblinded, controlled trial conducted in approximately 35-50&#xD;
      intensive care units (ICUs) and will recruit 4000 mechanically ventilated patients (life&#xD;
      support) who are expected to remain on the ventilator &gt; 24 hours AND require immediate&#xD;
      ongoing sedative medication for comfort, safety, and to facilitate the delivery of life&#xD;
      support measures, including mechanical ventilation.&#xD;
&#xD;
      Patients with primary brain injury or prolonged weakness are excluded. Participants will be&#xD;
      randomized into one of 2 study groups. All patients will receive adequate analgesia at&#xD;
      randomization at the discretion of treating clinician. All randomized patients will have&#xD;
      Light sedation as the default target unless otherwise clinically indicated. The intervention&#xD;
      group will receive EGDS with dexmedetomidine as the primary sedative agent to achieve light&#xD;
      sedation, with the addition of propofol as required. The use of benzodiazepines in the&#xD;
      intervention group is not allowed, with the exception of specific, defined circumstances.&#xD;
&#xD;
      The control group will have sedation according to usual practice as chosen by the treating&#xD;
      clinician. The use of dexmedetomidine is not allowed, with the exception of specific, defined&#xD;
      circumstances.&#xD;
&#xD;
      Deidentified data will be collected and will include; Baseline demographic information; Doses&#xD;
      of all sedative, analgesic and other related medications; Pain, sedation and delirium scores&#xD;
      and major treatments such as ventilation time, tracheostomy and dialysis. Patients surviving&#xD;
      to hospital discharge will be contacted by phone to determine independent survival status at&#xD;
      90 days and again at 180 days plus Health Related Quality of Life and cognitive function&#xD;
      assessment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2013</start_date>
  <completion_date type="Actual">December 2018</completion_date>
  <primary_completion_date type="Actual">August 2018</primary_completion_date>
  <phase>Phase 3</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mortality</measure>
    <time_frame>Day 90 post randomisation</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ventilation free days</measure>
    <time_frame>at 28 days following randomisation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of RASS measurements in target range</measure>
    <time_frame>up to day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and duration of delirium measured by delirium free days</measure>
    <time_frame>up to 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of ICU stay</measure>
    <time_frame>up to 180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who receive a tracheostomy Proportion of patients who require: re-intubation, physical restraints,or unplanned extubation,</measure>
    <time_frame>up to day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative dose of midazolam, propofol, dexmedetomidine, fentanyl, and morphine</measure>
    <time_frame>up to 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of treatment with midazolam, propofol, dexmedetomidine, fentanyl, and morphine</measure>
    <time_frame>up to 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality at hospital discharge</measure>
    <time_frame>at hospital discharge up to 180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>up to 180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Readmission to ICU</measure>
    <time_frame>at 90 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EQ-5D questionnaire</measure>
    <time_frame>at 180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function</measure>
    <time_frame>at 180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality at ICU discharge</measure>
    <time_frame>up to 180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Full time institutional dependency at 180 days</measure>
    <time_frame>up to 180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Discharge destination</measure>
    <time_frame>up to 180 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4000</enrollment>
  <condition>Critical Illness and Mechanical Ventilation</condition>
  <arm_group>
    <arm_group_label>Early Goal Directed Sedation</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Early Goal Directed Sedation process of care involves:&#xD;
Early delivery of proposed intervention, shortly after initiating mechanical ventilation;&#xD;
Effective analgesia provided simultaneously and early (analgesia first).&#xD;
Regular and frequent assessment of patient wakefulness/sedative state;&#xD;
Avoidance of benzodiazepines and minimisation of use of propofol;&#xD;
Reduced overall sedation depth with targeted light sedation; Patients randomised to the EGDS arm will receive a sedative infusion of Dexmedetomidine withor without minimal propofol in order to maintain a RASS of -2 to +1.&#xD;
Dexmedetomidine infusion will be continued until sedation is no longer clinically indicated up to a maximum of 28 days after enrolment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard care Sedation Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomised to the standard care sedation arm will receive process of care sedation directed by the treating clinician. Based on the information from our observational study and the EGDS Pilot trial, most patients in this group are likely to receive midazolam and /or propofol. These agents will be infused to achieve the default target of Light sedation (RASS -2 to +1) whenever clinically appropriate and as specified by the treating clinician. The use remifentanil or dexmedetomidine for initial and maintenance sedation will be precluded.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Early goal Directed Sedation</intervention_name>
    <arm_group_label>Early Goal Directed Sedation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard care sedation</intervention_name>
    <arm_group_label>Standard care Sedation Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient has been intubated and is receiving mechanical ventilation&#xD;
&#xD;
          -  The treating clinician expects that the patient will remain intubated until the day&#xD;
             after tomorrow (unlikely to be extubated the following day).&#xD;
&#xD;
          -  The patient requires immediate ongoing sedative medication for comfort, safety, and to&#xD;
             facilitate the delivery of life support measures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age less than 18 years&#xD;
&#xD;
          -  Patient is pregnant and/or lactating&#xD;
&#xD;
          -  Has been intubated (excluding time spent intubated within an operating theatre or&#xD;
             transport) for greater than 12 hours in an intensive care unit.&#xD;
&#xD;
          -  Proven or suspected acute primary brain lesion such as traumatic brain injury,&#xD;
             intracranial haemorrhage, stroke, or hypoxic brain injury.&#xD;
&#xD;
          -  Proven or suspected spinal cord injury or other pathology that may result in permanent&#xD;
             or prolonged weakness.&#xD;
&#xD;
          -  Admission as a consequence of a suspected or proven drug overdose or burns.&#xD;
&#xD;
          -  Administration of ongoing neuromuscular blockade.&#xD;
&#xD;
          -  A mean arterial blood (MAP) pressure that is less than 50 mmHg despite adequate&#xD;
             resuscitation and vasopressor therapy at time of randomisation&#xD;
&#xD;
          -  Heart rate less than 55 beats per minute unless the patient is being treated with a&#xD;
             beta-blocker or a high grade atrio-ventricular block in the absence of a functioning&#xD;
             pacemaker.&#xD;
&#xD;
          -  Known sensitivity to any of the study medications or the constituents of propofol&#xD;
             (egg, soya or peanut protein)&#xD;
&#xD;
          -  Acute fulminant hepatic failure&#xD;
&#xD;
          -  Patient has been receiving full time residential nursing care.&#xD;
&#xD;
          -  Death is deemed to be imminent or inevitable during this admission and either the&#xD;
             attending physician, patient or substitute decision maker is not committed to active&#xD;
             treatment.&#xD;
&#xD;
          -  Patient has an underlying disease that makes survival to 90 days unlikely&#xD;
&#xD;
          -  Patient has been previously enrolled in the SPICE study.&#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>Yahya Shehabi, MD, FCICM, FANZCA, EMBA</last_name>
    <role>Study Chair</role>
    <affiliation>University New South Wales, Prince of Wales Hospital, ANZIC-RC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rinaldo Bellomo</last_name>
    <role>Principal Investigator</role>
    <affiliation>ANZIC-RC &amp; Austin Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Steve A. R Webb</last_name>
    <role>Principal Investigator</role>
    <affiliation>ANZIC-RC &amp; Royal Perth Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michael C Reade</last_name>
    <role>Principal Investigator</role>
    <affiliation>ANZIC-RC, Royal Brisbane &amp; Women's Hospital, Department of Military Medicine and Surgery,</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Belinda D Howe</last_name>
    <role>Principal Investigator</role>
    <affiliation>ANZIC-RC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ian M Seppelt</last_name>
    <role>Principal Investigator</role>
    <affiliation>ANZIC-RC, Nepean Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Colin McArthur</last_name>
    <role>Principal Investigator</role>
    <affiliation>ANZIC-RC, Auckland Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Simon Erikson</last_name>
    <role>Principal Investigator</role>
    <affiliation>ANZIC-RC,</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lynne Murray</last_name>
    <role>Principal Investigator</role>
    <affiliation>ANZIC-RC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Suhaini Kadiman</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut Jantung Negara, Malaysia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jukka Takala</last_name>
    <role>Principal Investigator</role>
    <affiliation>Inselspital, Bern, Switzerland</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yaseen Arabi</last_name>
    <role>Principal Investigator</role>
    <affiliation>King Abdulaziz Medical Centre, KSA</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Matthew P Wise</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital of Wales, UK</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Albury Hospital</name>
      <address>
        <city>Albury</city>
        <state>New South Wales</state>
        <zip>2640</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blacktown Hospital</name>
      <address>
        <city>Blacktown</city>
        <state>New South Wales</state>
        <zip>2148</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent's Hospital Sydney</name>
      <address>
        <city>Darlinghurst</city>
        <state>New South Wales</state>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gosford Hospital</name>
      <address>
        <city>Gosford</city>
        <state>New South Wales</state>
        <zip>2250</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hornsby Ku-ring-gai Hospital</name>
      <address>
        <city>Hornsby</city>
        <state>New South Wales</state>
        <zip>2077</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nepean Hospital</name>
      <address>
        <city>Penrith</city>
        <state>New South Wales</state>
        <zip>2750</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal North Shore Hospital</name>
      <address>
        <city>St. Leonards</city>
        <state>New South Wales</state>
        <zip>2065</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prince of Wales Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westmead Hospital</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Darwin Hospital</name>
      <address>
        <city>Tiwi</city>
        <state>Northern Territory</state>
        <zip>0811</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunshine Coast Hospital (Nambour Hospital)</name>
      <address>
        <city>Buderim</city>
        <state>Queensland</state>
        <zip>4556</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane and Women's hospital</name>
      <address>
        <city>Herston</city>
        <state>Queensland</state>
        <zip>4029</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Redcliffe Hospital</name>
      <address>
        <city>Redcliffe</city>
        <state>Queensland</state>
        <zip>4020</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gold Coast Hospital &amp; Health Service</name>
      <address>
        <city>Southport</city>
        <state>Queensland</state>
        <zip>4215</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toowoomba Hospital</name>
      <address>
        <city>Toowoomba</city>
        <state>Queensland</state>
        <zip>4350</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Alexandra Hospital</name>
      <address>
        <city>Woolloongabba</city>
        <state>Queensland</state>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lyell McEwan Hospital</name>
      <address>
        <city>Elizabeth Vale</city>
        <state>South Australia</state>
        <zip>5112</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Hobart Hospital</name>
      <address>
        <city>Hobart</city>
        <state>Tasmania</state>
        <zip>7000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Launceston General Hospital</name>
      <address>
        <city>Launceston</city>
        <state>Tasmania</state>
        <zip>7250</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bendigo Hospital</name>
      <address>
        <city>Bendigo</city>
        <state>Victoria</state>
        <zip>3550</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dandenong Hospital</name>
      <address>
        <city>Dandenong</city>
        <state>Victoria</state>
        <zip>3175</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northern Hospital</name>
      <address>
        <city>Epping</city>
        <state>Victoria</state>
        <zip>3076</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geelong Hospital</name>
      <address>
        <city>Geelong</city>
        <state>Victoria</state>
        <zip>3220</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Hospital</name>
      <address>
        <city>Heidelberg</city>
        <state>Victoria</state>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Melbourne Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Medical Centre</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Gippsland Health Service</name>
      <address>
        <city>Sale</city>
        <state>Victoria</state>
        <zip>3850</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Knox Private Hospital</name>
      <address>
        <city>Wantirna</city>
        <state>Victoria</state>
        <zip>3152</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St John Of God, Subiaco</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6008</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent's University Hospital</name>
      <address>
        <city>Dublin</city>
        <state>Dublin 4</state>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St James's University Hospital</name>
      <address>
        <city>Dublin</city>
        <state>Dublin 8</state>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Raffaele</name>
      <address>
        <city>Milan</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Raja Perempuan Zainab II Hospital</name>
      <address>
        <city>Kota Bharu</city>
        <state>Kelantan</state>
        <zip>15200</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universiti Sains Malaysia Hospital</name>
      <address>
        <city>Kota Bharu</city>
        <state>Kelantan</state>
        <zip>16150</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penang General Hospital</name>
      <address>
        <city>George Town</city>
        <state>Pulau Pinang</state>
        <zip>10990</zip>
        <country>Malaysia</country>
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    <facility>
      <name>Queen Elizabeth Hospital</name>
      <address>
        <city>Kota Kinabalu</city>
        <state>Sabah</state>
        <zip>88200</zip>
        <country>Malaysia</country>
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    <facility>
      <name>Sarawak General Hospital</name>
      <address>
        <city>Kuching</city>
        <state>Sarawak</state>
        <zip>93586</zip>
        <country>Malaysia</country>
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    </facility>
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    <facility>
      <name>Institut Jantung Negara</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>50400</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kuala Lumpar General Hospital</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>50586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Malaya Medical Center</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>50603</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Melaka General Hospital</name>
      <address>
        <city>Melaka</city>
        <zip>75400</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Auckland City Hospital CVICU</name>
      <address>
        <city>Grafton</city>
        <state>Auckland</state>
        <zip>1023</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Middlemore Hospital</name>
      <address>
        <city>Otahuhu</city>
        <state>Auckland</state>
        <zip>1640</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christchurch Hospital</name>
      <address>
        <city>Addington</city>
        <state>Christchurch</state>
        <zip>8011</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Shore Hospital</name>
      <address>
        <city>Takapuna</city>
        <state>North Shore City</state>
        <zip>0622</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellington Hospital</name>
      <address>
        <city>Newtown</city>
        <state>Wellington</state>
        <zip>6021</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Auckland City hospital</name>
      <address>
        <city>Auckland</city>
        <zip>1023</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dunedin Hospital</name>
      <address>
        <city>Dunedin</city>
        <zip>9016</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rotorua Hospital</name>
      <address>
        <city>Rotorua</city>
        <zip>3010</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prince Sultan Military Medical City</name>
      <address>
        <city>Riyadh</city>
        <zip>12233</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King Saud Medical City</name>
      <address>
        <city>Riyadh</city>
        <zip>12746</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King Abdulaziz Medical City</name>
      <address>
        <city>Riyadh</city>
        <zip>14611</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inselspital University Hospital Bern</name>
      <address>
        <city>Bern</city>
        <zip>3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kings College Hospital</name>
      <address>
        <city>Brixton</city>
        <state>London</state>
        <zip>SE5 9RS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Freeman Hospital</name>
      <address>
        <city>High Heaton</city>
        <state>Newcastle Upon Tyne</state>
        <zip>NE7 7DN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital King's Lynn</name>
      <address>
        <city>King's Lynn</city>
        <state>Norfolk</state>
        <zip>PE30 4ET</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Derriford Hospital</name>
      <address>
        <city>Crownhill</city>
        <state>Plymouth</state>
        <zip>PL6 8DH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of North Tees</name>
      <address>
        <city>Hardwick</city>
        <state>Stockton-on-Tees</state>
        <zip>TS19 8PE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital, Birmingham</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Bournemouth Hospital</name>
      <address>
        <city>Bournemouth</city>
        <zip>BH7 7DW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Bristol</name>
      <address>
        <city>Bristol</city>
        <zip>BS1 3NU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of Wales</name>
      <address>
        <city>Cardiff</city>
        <zip>CF14 4XW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of Coventry and Warwick</name>
      <address>
        <city>Coventry</city>
        <zip>CV2 2DX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dorset County Hospital</name>
      <address>
        <city>Dorchester</city>
        <zip>DT1 2JY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Infirmary of Edinburgh</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH16 4SA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western General Hospital</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH4 2XU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Liverpool University Hospital</name>
      <address>
        <city>Liverpool</city>
        <zip>L7 8XP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Altnagelvin Hospital</name>
      <address>
        <city>Londonderry</city>
        <zip>BT47 6SB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Thomas Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 7EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St George's Hospital</name>
      <address>
        <city>London</city>
        <zip>SW17 0QT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College Hospital</name>
      <address>
        <city>London</city>
        <zip>WC1E 6BT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Victoria Infirmary</name>
      <address>
        <city>Newcastle Upon Tyne</city>
        <zip>NE1 4LP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Royal University Hospital</name>
      <address>
        <city>Orpington</city>
        <zip>BR6 8ND</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Berkshire Hospital</name>
      <address>
        <city>Reading</city>
        <zip>RG1 5LE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Ireland</country>
    <country>Italy</country>
    <country>Malaysia</country>
    <country>New Zealand</country>
    <country>Saudi Arabia</country>
    <country>Switzerland</country>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C, Seppelt IM, Webb S, Weisbrodt L; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012 Oct 15;186(8):724-31. doi: 10.1164/rccm.201203-0522OC. Epub 2012 Aug 2.</citation>
    <PMID>22859526</PMID>
  </reference>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>November 4, 2012</study_first_submitted>
  <study_first_submitted_qc>November 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <last_update_submitted>August 18, 2019</last_update_submitted>
  <last_update_submitted_qc>August 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sedation</keyword>
  <keyword>Delirium</keyword>
  <keyword>Goal Directed</keyword>
  <keyword>Dexmedetomidine</keyword>
  <keyword>Mortality</keyword>
  <keyword>Mechanical ventilation</keyword>
  <keyword>Intensive care</keyword>
  <keyword>Critically Ill</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <!-- 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/NCT01728558
org study id: ANZIC-RC/YS003
nct id: NCT01728558
lead sponsor: 
collaborator: 
has dmc: Yes
The Use of sedative drugs in intensive care is widespread. A cohort study conducted in
      Australia and New Zealand in 2010 revealed a high prevalence of deep sedation within the
      first 48 hours of mechanical ventilation which was independently linked to prolonged
      ventilation, hospital and 180 days mortality. Clinical practice is moving towards the use of
      lighter levels of sedation. Recent RCTs in Europe (JAMA 2012) and previous RCTs (JAMA 2009)
      supports growing evidence that dexmedetomidine facilitates rousable sedation, shortens
      ventilation time and attenuates delirium when compared to midazolam and propofol.

      The investigators confirmed in a pilot study the feasibility, efficacy and safety of a
      process of care known as Early Goal Directed Sedation (EGDS) that delivers:

        1. Early randomization after intubation or arrival in the ICU (intubated).

        2. Early Adequate analgesia after randomization.

        3. Goal directed sedation titrated to achieve light sedation.

        4. Dexmedetomidine based algorithm as the primary sedative agent with avoidance of
           benzodiazepines.

      The aim of this study is to assess the effectiveness of Early Goal Directed Sedation when
      compared to standard care sedation in critically ill patients.

      The study hypothesis is that Early Goal-Directed Sedation (EGDS), compared to standard care
      sedation, reduces 90-day all-cause mortality in critically ill patients who require
      mechanical ventilation.
This is a large-scale study into the effectiveness of a novel approach for sedation in
      ventilated critically ill patients. The primary aim of this study is to determine whether
      Early Goal Directed Sedation therapy, compared to standard care sedation, reduces 90-day
      mortality in critically ill patients ventilated > 24 hrs.

      The study will be a randomized, unblinded, controlled trial conducted in approximately 35-50
      intensive care units (ICUs) and will recruit 4000 mechanically ventilated patients (life
      support) who are expected to remain on the ventilator > 24 hours AND require immediate
      ongoing sedative medication for comfort, safety, and to facilitate the delivery of life
      support measures, including mechanical ventilation.

      Patients with primary brain injury or prolonged weakness are excluded. Participants will be
      randomized into one of 2 study groups. All patients will receive adequate analgesia at
      randomization at the discretion of treating clinician. All randomized patients will have
      Light sedation as the default target unless otherwise clinically indicated. The intervention
      group will receive EGDS with dexmedetomidine as the primary sedative agent to achieve light
      sedation, with the addition of propofol as required. The use of benzodiazepines in the
      intervention group is not allowed, with the exception of specific, defined circumstances.

      The control group will have sedation according to usual practice as chosen by the treating
      clinician. The use of dexmedetomidine is not allowed, with the exception of specific, defined
      circumstances.

      Deidentified data will be collected and will include; Baseline demographic information; Doses
      of all sedative, analgesic and other related medications; Pain, sedation and delirium scores
      and major treatments such as ventilation time, tracheostomy and dialysis. Patients surviving
      to hospital discharge will be contacted by phone to determine independent survival status at
      90 days and again at 180 days plus Health Related Quality of Life and cognitive function
      assessment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mortality
time frame: Day 90 post randomisation
measure: Ventilation free days
time frame: at 28 days following randomisation
measure: Proportion of RASS measurements in target range
time frame: up to day 28
measure: Incidence and duration of delirium measured by delirium free days
time frame: up to 28 days
measure: Length of ICU stay
time frame: up to 180 days
measure: Proportion of patients who receive a tracheostomy Proportion of patients who require: re-intubation, physical restraints,or unplanned extubation,
time frame: up to day 28
measure: Cumulative dose of midazolam, propofol, dexmedetomidine, fentanyl, and morphine
time frame: up to 28 days
measure: Duration of treatment with midazolam, propofol, dexmedetomidine, fentanyl, and morphine
time frame: up to 28 days
measure: Mortality at hospital discharge
time frame: at hospital discharge up to 180 days
measure: Length of hospital stay
time frame: up to 180 days
measure: Readmission to ICU
time frame: at 90 days
measure: EQ-5D questionnaire
time frame: at 180 days
measure: Cognitive function
time frame: at 180 days
measure: Mortality at ICU discharge
time frame: up to 180 days
measure: Full time institutional dependency at 180 days
time frame: up to 180 days
measure: Discharge destination
time frame: up to 180 days
arm group label: Early Goal Directed Sedation
arm group type: Other
description: Early Goal Directed Sedation process of care involves:
Early delivery of proposed intervention, shortly after initiating mechanical ventilation;
Effective analgesia provided simultaneously and early (analgesia first).
Regular and frequent assessment of patient wakefulness/sedative state;
Avoidance of benzodiazepines and minimisation of use of propofol;
Reduced overall sedation depth with targeted light sedation; Patients randomised to the EGDS arm will receive a sedative infusion of Dexmedetomidine withor without minimal propofol in order to maintain a RASS of -2 to +1.
Dexmedetomidine infusion will be continued until sedation is no longer clinically indicated up to a maximum of 28 days after enrolment.
arm group label: Standard care Sedation Arm
arm group type: Active Comparator
description: Patients randomised to the standard care sedation arm will receive process of care sedation directed by the treating clinician. Based on the information from our observational study and the EGDS Pilot trial, most patients in this group are likely to receive midazolam and /or propofol. These agents will be infused to achieve the default target of Light sedation (RASS -2 to +1) whenever clinically appropriate and as specified by the treating clinician. The use remifentanil or dexmedetomidine for initial and maintenance sedation will be precluded.
intervention type: Other
intervention name: Early goal Directed Sedation
arm group label: Early Goal Directed Sedation
intervention type: Other
intervention name: Standard care sedation
arm group label: Standard care Sedation Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yahya Shehabi, MD, FCICM, FANZCA, EMBA
role: Study Chair
affiliation: University New South Wales, Prince of Wales Hospital, ANZIC-RC
last name: Rinaldo Bellomo
role: Principal Investigator
affiliation: ANZIC-RC & Austin Hospital
last name: Steve A. R Webb
role: Principal Investigator
affiliation: ANZIC-RC & Royal Perth Hospital
last name: Michael C Reade
role: Principal Investigator
affiliation: ANZIC-RC, Royal Brisbane & Women's Hospital, Department of Military Medicine and Surgery,
last name: Belinda D Howe
role: Principal Investigator
affiliation: ANZIC-RC
last name: Ian M Seppelt
role: Principal Investigator
affiliation: ANZIC-RC, Nepean Hospital
last name: Colin McArthur
role: Principal Investigator
affiliation: ANZIC-RC, Auckland Hospital
last name: Simon Erikson
role: Principal Investigator
affiliation: ANZIC-RC,
last name: Lynne Murray
role: Principal Investigator
affiliation: ANZIC-RC
last name: Suhaini Kadiman
role: Principal Investigator
affiliation: Institut Jantung Negara, Malaysia
last name: Jukka Takala
role: Principal Investigator
affiliation: Inselspital, Bern, Switzerland
last name: Yaseen Arabi
role: Principal Investigator
affiliation: King Abdulaziz Medical Centre, KSA
last name: Matthew P Wise
role: Principal Investigator
affiliation: University Hospital of Wales, UK
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country: Australia
country: Ireland
country: Italy
country: Malaysia
country: New Zealand
country: Saudi Arabia
country: Switzerland
country: United Kingdom
citation: Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C, Seppelt IM, Webb S, Weisbrodt L; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012 Oct 15;186(8):724-31. doi: 10.1164/rccm.201203-0522OC. Epub 2012 Aug 2.
PMID: 22859526
responsible party type: Sponsor
mesh term: Critical Illness