The Augmented Versus Routine Approach to Giving Energy Trial

Critical Illness Clinical Trial

— TARGET  

Official title:

The Augmented Versus Routine Approach to Giving Energy Trial: A Randomised Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02306746
• Other study ID #: ANZIC-RC/MC001
• Status: Completed
• Phase: Phase 3
• Start date: June 16, 2016
• Est. completion date: August 1, 2018

Study information

• Verified date: September 2018
• Source: Australian and New Zealand Intensive Care Research Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4000
• Est. completion date: August 1, 2018
• Est. primary completion date: July 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness

Intervention

Dietary Supplement:
• TARGET protocol EN 1.5 kcal/mL
Enteral feed 1.5 kcal/mL
• TARGET protocol EN 1.0 kcal/mL
Enteral feed 1.0 kcal/mL

Locations

Country	Name	City	State
Australia	Lyell McEwin	Adelaide	South Australia
Australia	Queen Elizabeth Hospital	Adelaide	South Australia
Australia	Royal Adelaide Hosptial	Adelaide	South Australia
Australia	Bendigo Hospital	Bendigo	Victoria
Australia	Logan Hospital	Brisbane	Queensland
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Bunbury Hospital	Bunbury	Western Australia
Australia	Canberra Hospital	Canberra	Australian Capital Territory
Australia	Footscray Hospital	Footscray	Victoria
Australia	Frankston Hosptial	Frankston	Victoria
Australia	University Hosptial Geelong	Geelong	Victoria
Australia	Gosford Hospital	Gosford	New South Wales
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Launceston General Hospital	Launceston	Tasmania
Australia	Monash Health Dandenong Hospital	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	St Vincent's Hospital Melbourne	Melbourne	Victoria
Australia	Sunshine Hospital	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Perth	Western Australia
Australia	Sir Charles Gairdner Hospital	Perth	Western Australia
Australia	St John of God Hospital Murdoch	Perth	Western Australia
Australia	Blacktown Hospital	Sydney	New South Wales
Australia	Concord Hospital	Sydney	New South Wales
Australia	Liverpool Hospital	Sydney	New South Wales
Australia	Nepean Hospital	Sydney	New South Wales
Australia	Royal North Shore Hosptial	Sydney	New South Wales
Australia	Royal Prince Alfred Hospital	Sydney	New South Wales
Australia	St George Hospital	Sydney	New South Wales
Australia	St Vincent's Hospital Sydney	Sydney	New South Wales
Australia	Sydney Adventist Hospital	Sydney	New South Wales
Australia	Westmead Hospital	Sydney	New South Wales
Australia	Toowoomba Hospital	Toowoomba	Queensland
New Zealand	Auckland City Hospital Cardiovascular Intensive Care Unit	Auckland
New Zealand	Auckland City Hospital Department of Critical Care Medicine	Auckland
New Zealand	Middlemore Hospital	Auckland
New Zealand	North Shore Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Waikato Hospital	Hamilton
New Zealand	Hawkes Bay Fallen Soldiers Memorial Hospital	Hastings
New Zealand	Hutt Valley Hospital	Lower Hutt
New Zealand	Nelson Hospital	Nelson
New Zealand	Rotorua Hospital	Rotorua
New Zealand	Tauranga Hospital	Tauranga
New Zealand	Wellington Regional Hospital	Wellington

Sponsors (1)

Lead Sponsor	Collaborator
Australian and New Zealand Intensive Care Research Centre

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All cause mortality	Mortality status	Day 90
Secondary	Mortality	Mortality status	At hospital discharge an average of 28 days
Secondary	Mortality	Mortality status	Day 28
Secondary	Time from randomisation until death	Mortality status	Day 180
Secondary	Number of days alive and not in ICU	Mortality status	Day 28
Secondary	Number of days alive and not in hospital	Mortality status	Day 28
Secondary	Ventilator free days	Organ support status	Day 28
Secondary	Proportion of patients receiving vasopressor support	Organ support proportion	Day 28
Secondary	Vasopressor free days	Organ support status	Day 28
Secondary	Proportion of patients receiving any renal replacement therapy	Organ support proportion	Day 28
Secondary	Renal replacement therapy free days	Organ support status	Day 28
Secondary	Proportion of patients with positive blood cultures	Blood stream infection proportion	Day 28
Secondary	Proportion of patients requiring intravenous antimicrobials	Patients requiring intravenous antimicrobials	Day 28
Secondary	Mortality	Mortality status	Day 180
Secondary	Quality of life assessment	European Quality of Life 5 Dimensions	Day 180
Secondary	Functional outcomes for patients under 65 years in the work force	Questions from the Australian Labour Force Survey	Day 180
Secondary	Functional outcomes for patients under 65 years and not in the work force and patients 65 years and over living dependently	World Health Organization Disability Assessment Schedule 2.0	Day 180
Secondary	Functional outcomes for patients 65 years and over living independently	Adelaide Activities Profile	Day 180
Secondary	Cause-specific mortality	Mortality status	Day 90

External Links

•   Protocol publication, March 2018
•   Statistical analysis plan publication, March 2018