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The Augmented Versus Routine Approach to Giving Energy Trial (TARGET)

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ClinicalTrials.gov Identifier: NCT02306746
Recruitment Status : Completed
First Posted : December 3, 2014
Last Update Posted : September 13, 2018
Sponsor:
Information provided by (Responsible Party):
Australian and New Zealand Intensive Care Research Centre

Brief Summary:

Nutrition therapy is an essential standard of care for all critically ill patients who are mechanically ventilated and remain in the intensive care unit for more than a few days.

The investigators plan to conduct a 4,000 patient, double-blind, randomised controlled trial to determine if augmentation of calorie delivery using energy dense enteral nutrition in mechanically ventilated patients improves 90 day survival when compared to routine care.


Condition or disease Intervention/treatment Phase
Critical Illness Dietary Supplement: TARGET protocol EN 1.5 kcal/mL Dietary Supplement: TARGET protocol EN 1.0 kcal/mL Phase 3

Detailed Description:

Each year around 130,000 Australians are admitted to ICU at a daily cost of approximately $4000 per patient. Their care consumes close to 3 billion dollars per year. These critically ill patients are the sickest in the hospital. They require substantial resources and multiple interventions. Some die and many of those who survive have delayed and compromised functional recovery which can persist for months or years.

Nutrition therapy is an essential standard of care for all ICU patients who are mechanically ventilated and remain in ICU for more than a few days. Enteral nutrition (via a nasogastric tube) is usually initiated within 24 hours of ICU admission with a formula containing 1 kcal/ml and prescribed at an approximate rate of 1 ml/kg/hour. However, standard enteral nutrition practice typically results in the delivery of only ~60% of the full-recommended calorie requirement.

Although prescribed calories can reliably be delivered using the intravenous route, the enteral route is preferred for a number of reasons and is recommended by all nutrition guidelines as first-line therapy. In particular, enteral nutrition is more physiological, less costly and associated with fewer infective complications. Delivery of nutrient into the gut also has beneficial effects on subsequent gut function and may reduce ongoing sepsis which can be fuelled by the movement of gut flora through a permeable mucosa that has not been exposed to nutrient. Intravenous nutrition is accordingly, generally used only when enteral feeding is impossible, or persistently limited. Although supplementing enteral with intravenous nutrition can increase calorie delivery, this has not been shown to have a therapeutic benefit and may worsen important clinical outcomes. This may be because adverse effects associated with intravenous nutrition counteract the benefits of increased calorie delivery.

Previous trials support the concept that optimising nutrition in the critically ill will improve outcome, however, the evidence is limited, inclusive and generally of low quality. It is extraordinary that there is not better (Level I) evidence to inform nutrition management in critically ill patients given the frequency of the intervention, the biologic rationale, the high mortality following ICU admission, the frequency of muscle wasting and the poor functional outcomes in survivors. This is especially true given the low cost of enteral nutrition (~$23/day).

The investigators recently completed pilot study clearly achieved all the key criteria which, for a pharmaceutical product, would lead to a phase III trial, namely: 1. feasibility; 2. safety; 3. separation; 4. excellent recruitment rate; 5. successful blinding; 6. a signal for benefit.

A definitive study must now be done to establish whether 90-day survival and functional outcomes following critical illness may be improved by increased calorie delivery.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Augmented Versus Routine Approach to Giving Energy Trial: A Randomised Controlled Trial
Actual Study Start Date : June 16, 2016
Actual Primary Completion Date : July 10, 2018
Actual Study Completion Date : August 1, 2018

Arm Intervention/treatment
Experimental: TARGET protocol EN 1.5 kcal/mL
Enteral (EN) feed 1.5 kcal/mL. The goal rate for administration of TARGET protocol EN is 1ml/kg/hr. To calculate the goal rate, weight is based on ideal body weight.
Dietary Supplement: TARGET protocol EN 1.5 kcal/mL
Enteral feed 1.5 kcal/mL

Active Comparator: TARGET protocol EN 1.0 kcal/mL
Enteral feed 1.0 kcal/mL The goal rate for administration of TARGET protocol EN is 1ml/kg/hr. To calculate the goal rate, weight is based on ideal body weight.
Dietary Supplement: TARGET protocol EN 1.0 kcal/mL
Enteral feed 1.0 kcal/mL




Primary Outcome Measures :
  1. All cause mortality [ Time Frame: Day 90 ]
    Mortality status


Secondary Outcome Measures :
  1. Mortality [ Time Frame: At hospital discharge an average of 28 days ]
    Mortality status

  2. Mortality [ Time Frame: Day 28 ]
    Mortality status

  3. Time from randomisation until death [ Time Frame: Day 180 ]
    Mortality status

  4. Number of days alive and not in ICU [ Time Frame: Day 28 ]
    Mortality status

  5. Number of days alive and not in hospital [ Time Frame: Day 28 ]
    Mortality status

  6. Ventilator free days [ Time Frame: Day 28 ]
    Organ support status

  7. Proportion of patients receiving vasopressor support [ Time Frame: Day 28 ]
    Organ support proportion

  8. Vasopressor free days [ Time Frame: Day 28 ]
    Organ support status

  9. Proportion of patients receiving any renal replacement therapy [ Time Frame: Day 28 ]
    Organ support proportion

  10. Renal replacement therapy free days [ Time Frame: Day 28 ]
    Organ support status

  11. Proportion of patients with positive blood cultures [ Time Frame: Day 28 ]
    Blood stream infection proportion

  12. Proportion of patients requiring intravenous antimicrobials [ Time Frame: Day 28 ]
    Patients requiring intravenous antimicrobials

  13. Mortality [ Time Frame: Day 180 ]
    Mortality status

  14. Quality of life assessment [ Time Frame: Day 180 ]
    European Quality of Life 5 Dimensions

  15. Functional outcomes for patients under 65 years in the work force [ Time Frame: Day 180 ]
    Questions from the Australian Labour Force Survey

  16. Functional outcomes for patients under 65 years and not in the work force and patients 65 years and over living dependently [ Time Frame: Day 180 ]
    World Health Organization Disability Assessment Schedule 2.0

  17. Functional outcomes for patients 65 years and over living independently [ Time Frame: Day 180 ]
    Adelaide Activities Profile

  18. Cause-specific mortality [ Time Frame: Day 90 ]
    Mortality status



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Intubated and receiving mechanical ventilation
  • About to commence enteral nutrition or enteral nutrition commenced within the previous12 hours
  • Expected to be receiving enteral nutrition in ICU until at least the day after tomorrow

Exclusion Criteria:

  • Any Enteral Nutrition (EN) or Parenteral Nutrition (PN) received for >12 hours in this ICU admission
  • Treating clinician considers the EN goal rate (i.e.1ml/kg of ideal body weight per hour) to be clinically contraindicated e.g. requirement for fluid restriction
  • Requirement for specific nutritional therapy as determined by the treating doctor or dietitian i.e. TARGET protocol EN not considered to be in the best interest of the patient
  • Death is deemed to be imminent or inevitable during this admission and either the attending physician, patient or substitute decision maker is not committed to active treatment
  • The patient has an underlying disease that makes survival to 90 days unlikely
  • ≥ 15% burns
  • Previously enrolled in this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02306746


  Show 46 Study Locations
Sponsors and Collaborators
Australian and New Zealand Intensive Care Research Centre
Investigators
Study Chair: Sandra Peake, MD University of Adelaide

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Australian and New Zealand Intensive Care Research Centre
ClinicalTrials.gov Identifier: NCT02306746     History of Changes
Other Study ID Numbers: ANZIC-RC/MC001
First Posted: December 3, 2014    Key Record Dates
Last Update Posted: September 13, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Australian and New Zealand Intensive Care Research Centre:
Enteral nutrition
randomised control trial
Critical care
Outcome

Additional relevant MeSH terms:
Critical Illness
Disease Attributes
Pathologic Processes