<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/NCT03292237</url>
  </required_header>
  <id_info>
    <org_study_id>ANZIC-RC/ER001</org_study_id>
    <nct_id>NCT03292237</nct_id>
  </id_info>
  <brief_title>Intensive Nutrition in Critically Ill Adults</brief_title>
  <acronym>INTENT</acronym>
  <official_title>Intensive Nutrition Therapy Compared to Usual Care in Critically Ill Adults: A Randomised Pilot 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>Baxter Healthcare Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Australian and New Zealand Intensive Care Research Centre</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>
      Despite the widespread use of nutrition therapy, no large scale randomized controlled trials&#xD;
      (RCTs) have demonstrated positive outcomes with delivery of nutrition therapy early in&#xD;
      critical illness, with some showing no effect with delayed nutrition or even harm.&#xD;
&#xD;
      There are several possible reasons for the lack of observed benefit from RCTs to date;&#xD;
      interventions have been short in duration (usually 3-10 days after intensive care unit (ICU)&#xD;
      admission), perhaps applied at the incorrect time in regards to the patients metabolism and&#xD;
      recovery, do not consider the patients nutrition risk, and have not addressed what happens to&#xD;
      nutrition intake post ICU in critically ill individuals. This may explain why RCTs to date&#xD;
      have not observed any positive associations with the delivery of nutrition; our focus to date&#xD;
      may have been on the wrong stage of illness. A future study is thus urgently needed, which&#xD;
      addresses the deficiencies in current RCTs by optimizing nutrition delivery for the whole&#xD;
      hospital stay and collecting meaningful clinical, process and outcome data, which will&#xD;
      potentially inform a larger trial of a similar nature.&#xD;
&#xD;
      This initial study aims to determine whether optimization of energy using a pre-tested&#xD;
      supplemental parenteral nutrition (PN) strategy in the Intensive Care Unit (ICU) and an&#xD;
      intensive nutrition intervention in the post ICU period will deliver more total energy than&#xD;
      standard nutrition care during hospital admission in a group of critically ill patients with&#xD;
      at least one organ system failure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Nutrition is a commonly provided therapy in critical illness, but data about effectiveness is&#xD;
      sparse. Best practice guidelines recommend enteral nutrition (EN), a specialised solution&#xD;
      delivered into the gastrointestinal tract, as the first line of nutrition therapy. The&#xD;
      majority of best practice guidelines also recommend delivery of energy and protein amounts&#xD;
      close to predicted requirements in critical illness over the course of Intensive Care Unit&#xD;
      (ICU) admission, however the only evidence to support this is from observational data.&#xD;
      Although recommended that energy and protein requirements be met, and observational data&#xD;
      suggests this is of benefit, there are practical challenges with the provision of EN.&#xD;
      International practice surveys report the average energy and protein provided is&#xD;
      approximately 59% of the patients predicted requirements, for multifactorial reasons. The&#xD;
      addition of parenteral (intravenous) nutrition has been proposed as a method to provide&#xD;
      additional energy when EN is insufficient, termed supplemental parenteral nutrition (PN). The&#xD;
      ability of this strategy to deliver additional energy and protein to patients during critical&#xD;
      illness has been proven in several feasibility/pilot trials, but the benefit on clinical and&#xD;
      functional outcomes is unknown.&#xD;
&#xD;
      Despite observational data suggesting benefit when energy and protein delivery is optimised&#xD;
      close to requirements, no large scale randomised controlled trials (RCTs) have confirmed&#xD;
      improved clinical outcomes in critical illness, with some showing no effect with delayed&#xD;
      nutrition or even harm. There are several possible reasons for the lack of observed benefit&#xD;
      from RCTs to date; the interventions may have been applied at a time when the patient's&#xD;
      metabolism is not in a phase of recovery; interventions have been short in duration and;&#xD;
      studies have not addressed what happens to nutrition intake in the post ICU period of&#xD;
      hospitalisation in critically ill individuals.&#xD;
&#xD;
      Aims:&#xD;
&#xD;
      To determine whether the use of a pre-tested supplemental PN strategy in the ICU and an&#xD;
      intensive nutrition intervention after discharge to the hospital ward is feasible and will&#xD;
      deliver more total energy than standard nutrition care over the entire hospital stay, in&#xD;
      critically ill patients with at least one organ system failure.&#xD;
&#xD;
      A further aim is to develop a research program that will determine whether optimisation of&#xD;
      energy to critically ill patients over the entire period of hospitalisation improves&#xD;
      clinically-meaningful outcomes.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      In critically ill patients with at least one organ failure, the use of a supplemental PN&#xD;
      strategy in ICU and an intensive nutrition intervention on the hospital ward will lead to an&#xD;
      increase in daily energy delivery of at least 15% over the entire hospital stay when compared&#xD;
      to standard care.&#xD;
&#xD;
      Fifteen percent has been estimated as the minimum acceptable clinical difference between the&#xD;
      two groups.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      The major objectives are:&#xD;
&#xD;
        1. To determine whether the whole hospital nutrition intervention leads to increased&#xD;
           amounts of total energy delivered over the period of hospital stay&#xD;
&#xD;
        2. To determine if the whole hospital nutrition intervention is safe in regards to adverse&#xD;
           effects&#xD;
&#xD;
        3. To determine if the post-ICU nutrition intervention is practically feasible when applied&#xD;
           in multiple hospitals, across multiple wards&#xD;
&#xD;
        4. To measure the clinical outcomes in patients and provide information to assist design of&#xD;
           a larger randomised controlled trial&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 15, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">January 31, 2023</primary_completion_date>
  <phase>Phase 2</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>multicentre, prospective, parallel, randomised controlled trial</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Daily energy delivered from nutrition therapy</measure>
    <time_frame>Day 28</time_frame>
    <description>Daily energy delivered from nutrition therapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Nutrition intake</measure>
    <time_frame>Day 28</time_frame>
    <description>Daily protein intake, Energy and protein intake by location (ICU and ward)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration hospital stay</measure>
    <time_frame>Day 28</time_frame>
    <description>Duration of hospital stay in survivors and non-survivors</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator Free Days</measure>
    <time_frame>Day 28</time_frame>
    <description>Ventilator Free Days (VFDs) at study day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total blood stream infection rate</measure>
    <time_frame>Day 28</time_frame>
    <description>Total blood stream infection rate</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Duration of ICU stay</measure>
    <time_frame>Day 28</time_frame>
    <description>Duration of ICU stay in survivors and non survivors</description>
  </other_outcome>
  <other_outcome>
    <measure>Duration of Mechanical Ventilation</measure>
    <time_frame>Day 28</time_frame>
    <description>Duration of Mechanical Ventilation to study day 28 in survivors and non-survivors</description>
  </other_outcome>
  <other_outcome>
    <measure>ICU mobility scale</measure>
    <time_frame>Day 28</time_frame>
    <description>ICU mobility scale at ICU discharge</description>
  </other_outcome>
  <other_outcome>
    <measure>Mortality</measure>
    <time_frame>Day 28</time_frame>
    <description>In hospital and 28 day mortality</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood stream infections</measure>
    <time_frame>Day 28</time_frame>
    <description>Number of blood stream infections to day 28, time to any blood stream infection</description>
  </other_outcome>
  <other_outcome>
    <measure>Weight</measure>
    <time_frame>Day 28</time_frame>
    <description>Weight at hospital discharge</description>
  </other_outcome>
  <other_outcome>
    <measure>Frailty</measure>
    <time_frame>90 days</time_frame>
    <description>Clinical frailty score</description>
  </other_outcome>
  <other_outcome>
    <measure>European Quality Of Life 5 Dimensions 5 Level (EQ5D-5L)</measure>
    <time_frame>90 days</time_frame>
    <description>Health related quality of life assessment using EQ5D-5L. Each dimension has 5 levels ranging from no problems (1) to extreme problems (5), there is no overall score. It also has a visual analogue scale (VAS) ranging 0-100 with 0 being worst imaginable health state and 100 being best imaginable health state</description>
  </other_outcome>
  <other_outcome>
    <measure>World Health Organization Disability Assessment Schedule 2.0 (WHODAS)</measure>
    <time_frame>90 days</time_frame>
    <description>WHODAS is a 12 point disability assessment with a raw score range of 0-48. 0 is no disability and 48 being full disability</description>
  </other_outcome>
  <other_outcome>
    <measure>European Quality Of Life 5 Dimensions 5 Level (EQ5D-5L)</measure>
    <time_frame>180 days</time_frame>
    <description>Health related quality of life assessment using EQ5D-5L. Each dimension has 5 levels ranging from no problems (1) to extreme problems (5), there is no overall score. It also has a visual analogue scale (VAS) ranging 0-100 with 0 being worst imaginable health state and 100 being best imaginable health state</description>
  </other_outcome>
  <other_outcome>
    <measure>World Health Organization Disability Assessment Schedule 2.0 (WHODAS)</measure>
    <time_frame>180 days</time_frame>
    <description>WHODAS is a 12 point disability assessment with a raw score range of 0-48. 0 is no disability and 48 being full disability</description>
  </other_outcome>
  <other_outcome>
    <measure>Cost per quality adjusted life year</measure>
    <time_frame>180 days</time_frame>
    <description>Cost per quality adjusted life year (QALY)</description>
  </other_outcome>
  <other_outcome>
    <measure>Cost per life year gained</measure>
    <time_frame>180 days</time_frame>
    <description>Cost per life year gained (LYG)</description>
  </other_outcome>
  <other_outcome>
    <measure>Frailty</measure>
    <time_frame>180 dyas</time_frame>
    <description>Clinical frailty score</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">240</enrollment>
  <condition>Critical Illness</condition>
  <condition>Critically Ill</condition>
  <arm_group>
    <arm_group_label>Standard Nutrition Arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>In ICU:&#xD;
After enrolment, patients allocated to the standard nutrition therapy (control) group will commence or continue nutrition via an enteral tube to a target rate according to unit protocol including the use of promotility agents and the placement of nasojejunal feeding tubes if required.&#xD;
PN will only be used if the above methods have been attempted, or an absolute contraindication to EN develops.&#xD;
Unless there is specific indication for a compounded PN solution, the PN used in the standard care group will be the same as used in the intervention arm.&#xD;
After ICU:&#xD;
Nutrition management will be as per usual site management at that hospital.&#xD;
Nutrition intake amounts will be recorded 3 times per week using provided study documents and assessment tools.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intensive Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention&#xD;
In ICU:&#xD;
Supplemental PN will be commenced within 2 hours of randomisation. The starting dose of PN will be determined by the amount of energy received in the 24 hours prior to randomisation&#xD;
The need for the intervention will be based on the adequacy of nutrition provision from both PN and EN and assessed daily until ICU discharge&#xD;
If there is an actual or anticipated interruption of EN for greater than 2 hours the PN must be run at 20 kcal/kg calculated body weight until EN is recommenced. After the interruption, EN should be recommenced as per local protocol.&#xD;
After ICU:&#xD;
An intensive nutrition intervention will be provided on the ward in the intervention group. This will include daily review from dedicated study dietitians and a clearly protocolized hierarchical management plan which reflects best practice clinical management.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Supplemental parenteral nutrition</intervention_name>
    <description>Supplemental parenteral nutrition OLIMEL N12E (Baxter Healthcare Corporation)</description>
    <arm_group_label>Intensive Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
        Patients in intensive care who meet all of the following will be eligible:&#xD;
&#xD;
          1. Admitted to intensive care between 72 hours and 120 hours&#xD;
&#xD;
          2. Receiving invasive ventilator support&#xD;
&#xD;
          3. At least 18 years of age&#xD;
&#xD;
          4. Have central venous access suitable for PN solution administration&#xD;
&#xD;
          5. Have 1 or more organ system failure (respiratory, cardiovascular or renal) related to&#xD;
             their acute illness defined as:&#xD;
&#xD;
               -  PaO2/FiO2 ≤ 300 mmHg&#xD;
&#xD;
               -  Currently on 1 or more continuous inotrope/vasopressor infusion which were&#xD;
                  started at least 4 hours ago at a minimum dose of:&#xD;
&#xD;
                    1. Noradrenaline ≥ 0.1mcg/kg/min&#xD;
&#xD;
                    2. Adrenaline ≥ 0.1 mcg/kg/min&#xD;
&#xD;
                    3. Any dose of vasopressin&#xD;
&#xD;
                    4. Milrinone &gt; 0.1 mcg/kg/min&#xD;
&#xD;
               -  Renal dysfunction defined as:&#xD;
&#xD;
                    1. Serum creatinine 2.0-2.9 times baseline OR&#xD;
&#xD;
                    2. Urine output 0.5ml/kg/hr for ≥ 12 hours OR&#xD;
&#xD;
                    3. Currently receiving renal replacement therapy&#xD;
&#xD;
               -  Currently has an intracranial pressure monitor or ventricular drain in situ&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
        Patients will be excluded if:&#xD;
&#xD;
          -  Both EN and PN cannot be delivered at enrolment (i.e. either an enteral tube or a&#xD;
             central venous catheter cannot be placed or clinicians feel that EN or PN cannot be&#xD;
             safely administered due to any other reason)&#xD;
&#xD;
          -  Currently receiving PN&#xD;
&#xD;
          -  Clinician believes a specific parenteral formula is indicated&#xD;
&#xD;
          -  Death is imminent in the next 96 hours&#xD;
&#xD;
          -  There is a current treatment limitation in place or the patient is unlikely to survive&#xD;
             to 6 months due to underlying/chronic illness&#xD;
&#xD;
          -  More than 80% of energy requirements have been satisfactorily delivered via the&#xD;
             enteral route in the last 24 hours&#xD;
&#xD;
          -  Dialysis dependent chronic renal failure&#xD;
&#xD;
          -  Suspected or known pregnancy&#xD;
&#xD;
          -  Product contraindication&#xD;
&#xD;
          -  The treating clinician does not believe the study to be in the best interest of the&#xD;
             patient&#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>Emma Ridley, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>ANZIC-RC</affiliation>
  </overall_official>
  <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>Nepean Hospital</name>
      <address>
        <city>Kingswood</city>
        <state>New South Wales</state>
        <zip>2747</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Darwin Hospital</name>
      <address>
        <city>Darwin</city>
        <state>Northern Territory</state>
        <zip>0810</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prince Charles Hospital</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4032</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>Mater Hospital</name>
      <address>
        <city>South Brisbane</city>
        <state>Queensland</state>
        <zip>4101</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gold Coast University Hospital</name>
      <address>
        <city>Southport</city>
        <state>Queensland</state>
        <zip>4215</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 McEwin</name>
      <address>
        <city>Elizabeth Vale</city>
        <state>South Australia</state>
        <zip>5112</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital</name>
      <address>
        <city>Woodville South</city>
        <state>South Australia</state>
        <zip>5011</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ballarat Hospital</name>
      <address>
        <city>Ballarat</city>
        <state>Victoria</state>
        <zip>3350</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>Northern Hospital</name>
      <address>
        <city>Epping</city>
        <state>Victoria</state>
        <zip>3076</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Frankston Hospital - Peninsula Health</name>
      <address>
        <city>Frankston</city>
        <state>Victoria</state>
        <zip>3199</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>The Alfred Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Melbourne Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Epworth Richmond</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3121</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Box Hill Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3128</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>Auckland City Hospital CVICU</name>
      <address>
        <city>Auckland</city>
        <zip>1023</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Middlemore Hospital</name>
      <address>
        <city>Auckland</city>
        <zip>2025</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>New Zealand</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>September 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>February 8, 2023</last_update_submitted>
  <last_update_submitted_qc>February 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Energy</keyword>
  <keyword>Nutrition</keyword>
  <keyword>Critical illness</keyword>
  <keyword>Parenteral nutrition</keyword>
  <keyword>Intensive care unit</keyword>
  <keyword>Ward</keyword>
  <keyword>Randomised Controlled Trial</keyword>
  <keyword>Intensive Nutrition</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data sharing requests will be considered 2 years after publication of the primary trial data on an individual basis by the trial management committee (the data custodians). Data sharing will only be considered for investigator-initiated, independent researchers who provide a written data evaluation proposal that is judged to be methodologically sound. A data sharing agreement will be required to detail conditions under which data is shared and used. Resulting publications should appropriately cite and acknowledge the original data custodians. Requests for data sharing are to be made to anzicrc@monash.edu and the corresponding author, Dr Emma Ridley; emma.ridley@monash.edu</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03292237
org study id: ANZIC-RC/ER001
nct id: NCT03292237
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Despite the widespread use of nutrition therapy, no large scale randomized controlled trials
      (RCTs) have demonstrated positive outcomes with delivery of nutrition therapy early in
      critical illness, with some showing no effect with delayed nutrition or even harm.

      There are several possible reasons for the lack of observed benefit from RCTs to date;
      interventions have been short in duration (usually 3-10 days after intensive care unit (ICU)
      admission), perhaps applied at the incorrect time in regards to the patients metabolism and
      recovery, do not consider the patients nutrition risk, and have not addressed what happens to
      nutrition intake post ICU in critically ill individuals. This may explain why RCTs to date
      have not observed any positive associations with the delivery of nutrition; our focus to date
      may have been on the wrong stage of illness. A future study is thus urgently needed, which
      addresses the deficiencies in current RCTs by optimizing nutrition delivery for the whole
      hospital stay and collecting meaningful clinical, process and outcome data, which will
      potentially inform a larger trial of a similar nature.

      This initial study aims to determine whether optimization of energy using a pre-tested
      supplemental parenteral nutrition (PN) strategy in the Intensive Care Unit (ICU) and an
      intensive nutrition intervention in the post ICU period will deliver more total energy than
      standard nutrition care during hospital admission in a group of critically ill patients with
      at least one organ system failure.
Background:

      Nutrition is a commonly provided therapy in critical illness, but data about effectiveness is
      sparse. Best practice guidelines recommend enteral nutrition (EN), a specialised solution
      delivered into the gastrointestinal tract, as the first line of nutrition therapy. The
      majority of best practice guidelines also recommend delivery of energy and protein amounts
      close to predicted requirements in critical illness over the course of Intensive Care Unit
      (ICU) admission, however the only evidence to support this is from observational data.
      Although recommended that energy and protein requirements be met, and observational data
      suggests this is of benefit, there are practical challenges with the provision of EN.
      International practice surveys report the average energy and protein provided is
      approximately 59% of the patients predicted requirements, for multifactorial reasons. The
      addition of parenteral (intravenous) nutrition has been proposed as a method to provide
      additional energy when EN is insufficient, termed supplemental parenteral nutrition (PN). The
      ability of this strategy to deliver additional energy and protein to patients during critical
      illness has been proven in several feasibility/pilot trials, but the benefit on clinical and
      functional outcomes is unknown.

      Despite observational data suggesting benefit when energy and protein delivery is optimised
      close to requirements, no large scale randomised controlled trials (RCTs) have confirmed
      improved clinical outcomes in critical illness, with some showing no effect with delayed
      nutrition or even harm. There are several possible reasons for the lack of observed benefit
      from RCTs to date; the interventions may have been applied at a time when the patient's
      metabolism is not in a phase of recovery; interventions have been short in duration and;
      studies have not addressed what happens to nutrition intake in the post ICU period of
      hospitalisation in critically ill individuals.

      Aims:

      To determine whether the use of a pre-tested supplemental PN strategy in the ICU and an
      intensive nutrition intervention after discharge to the hospital ward is feasible and will
      deliver more total energy than standard nutrition care over the entire hospital stay, in
      critically ill patients with at least one organ system failure.

      A further aim is to develop a research program that will determine whether optimisation of
      energy to critically ill patients over the entire period of hospitalisation improves
      clinically-meaningful outcomes.

      Hypothesis:

      In critically ill patients with at least one organ failure, the use of a supplemental PN
      strategy in ICU and an intensive nutrition intervention on the hospital ward will lead to an
      increase in daily energy delivery of at least 15% over the entire hospital stay when compared
      to standard care.

      Fifteen percent has been estimated as the minimum acceptable clinical difference between the
      two groups.

      Objectives:

      The major objectives are:

        1. To determine whether the whole hospital nutrition intervention leads to increased
           amounts of total energy delivered over the period of hospital stay

        2. To determine if the whole hospital nutrition intervention is safe in regards to adverse
           effects

        3. To determine if the post-ICU nutrition intervention is practically feasible when applied
           in multiple hospitals, across multiple wards

        4. To measure the clinical outcomes in patients and provide information to assist design of
           a larger randomised controlled trial
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: multicentre, prospective, parallel, randomised controlled trial
primary purpose: Supportive Care
masking: None (Open Label)
measure: Daily energy delivered from nutrition therapy
time frame: Day 28
description: Daily energy delivered from nutrition therapy
measure: Nutrition intake
time frame: Day 28
description: Daily protein intake, Energy and protein intake by location (ICU and ward)
measure: Duration hospital stay
time frame: Day 28
description: Duration of hospital stay in survivors and non-survivors
measure: Ventilator Free Days
time frame: Day 28
description: Ventilator Free Days (VFDs) at study day 28
measure: Total blood stream infection rate
time frame: Day 28
description: Total blood stream infection rate
measure: Duration of ICU stay
time frame: Day 28
description: Duration of ICU stay in survivors and non survivors
measure: Duration of Mechanical Ventilation
time frame: Day 28
description: Duration of Mechanical Ventilation to study day 28 in survivors and non-survivors
measure: ICU mobility scale
time frame: Day 28
description: ICU mobility scale at ICU discharge
measure: Mortality
time frame: Day 28
description: In hospital and 28 day mortality
measure: Blood stream infections
time frame: Day 28
description: Number of blood stream infections to day 28, time to any blood stream infection
measure: Weight
time frame: Day 28
description: Weight at hospital discharge
measure: Frailty
time frame: 90 days
description: Clinical frailty score
measure: European Quality Of Life 5 Dimensions 5 Level (EQ5D-5L)
time frame: 90 days
description: Health related quality of life assessment using EQ5D-5L. Each dimension has 5 levels ranging from no problems (1) to extreme problems (5), there is no overall score. It also has a visual analogue scale (VAS) ranging 0-100 with 0 being worst imaginable health state and 100 being best imaginable health state
measure: World Health Organization Disability Assessment Schedule 2.0 (WHODAS)
time frame: 90 days
description: WHODAS is a 12 point disability assessment with a raw score range of 0-48. 0 is no disability and 48 being full disability
measure: European Quality Of Life 5 Dimensions 5 Level (EQ5D-5L)
time frame: 180 days
description: Health related quality of life assessment using EQ5D-5L. Each dimension has 5 levels ranging from no problems (1) to extreme problems (5), there is no overall score. It also has a visual analogue scale (VAS) ranging 0-100 with 0 being worst imaginable health state and 100 being best imaginable health state
measure: World Health Organization Disability Assessment Schedule 2.0 (WHODAS)
time frame: 180 days
description: WHODAS is a 12 point disability assessment with a raw score range of 0-48. 0 is no disability and 48 being full disability
measure: Cost per quality adjusted life year
time frame: 180 days
description: Cost per quality adjusted life year (QALY)
measure: Cost per life year gained
time frame: 180 days
description: Cost per life year gained (LYG)
measure: Frailty
time frame: 180 dyas
description: Clinical frailty score
arm group label: Standard Nutrition Arm
arm group type: No Intervention
description: In ICU:
After enrolment, patients allocated to the standard nutrition therapy (control) group will commence or continue nutrition via an enteral tube to a target rate according to unit protocol including the use of promotility agents and the placement of nasojejunal feeding tubes if required.
PN will only be used if the above methods have been attempted, or an absolute contraindication to EN develops.
Unless there is specific indication for a compounded PN solution, the PN used in the standard care group will be the same as used in the intervention arm.
After ICU:
Nutrition management will be as per usual site management at that hospital.
Nutrition intake amounts will be recorded 3 times per week using provided study documents and assessment tools.
arm group label: Intensive Arm
arm group type: Experimental
description: Intervention
In ICU:
Supplemental PN will be commenced within 2 hours of randomisation. The starting dose of PN will be determined by the amount of energy received in the 24 hours prior to randomisation
The need for the intervention will be based on the adequacy of nutrition provision from both PN and EN and assessed daily until ICU discharge
If there is an actual or anticipated interruption of EN for greater than 2 hours the PN must be run at 20 kcal/kg calculated body weight until EN is recommenced. After the interruption, EN should be recommenced as per local protocol.
After ICU:
An intensive nutrition intervention will be provided on the ward in the intervention group. This will include daily review from dedicated study dietitians and a clearly protocolized hierarchical management plan which reflects best practice clinical management.
intervention type: Dietary Supplement
intervention name: Supplemental parenteral nutrition
description: Supplemental parenteral nutrition OLIMEL N12E (Baxter Healthcare Corporation)
arm group label: Intensive Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Emma Ridley, PhD
role: Principal Investigator
affiliation: ANZIC-RC
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country: Australia
country: New Zealand
responsible party type: Sponsor
mesh term: Critical Illness
sharing ipd: Yes
ipd description: Data sharing requests will be considered 2 years after publication of the primary trial data on an individual basis by the trial management committee (the data custodians). Data sharing will only be considered for investigator-initiated, independent researchers who provide a written data evaluation proposal that is judged to be methodologically sound. A data sharing agreement will be required to detail conditions under which data is shared and used. Resulting publications should appropriately cite and acknowledge the original data custodians. Requests for data sharing are to be made to anzicrc@monash.edu and the corresponding author, Dr Emma Ridley; emma.ridley@monash.edu