The Augmented Versus Routine Approach to Giving Energy Trial
- Conditions
- Critical Illness
- Interventions
- Dietary Supplement: TARGET protocol EN 1.0 kcal/mLDietary Supplement: TARGET protocol EN 1.5 kcal/mL
- Registration Number
- NCT02306746
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4000
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TARGET protocol EN 1.0 kcal/mL 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. TARGET protocol EN 1.5 kcal/mL 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.
- Primary Outcome Measures
Name Time Method All cause mortality Day 90 Mortality status
- Secondary Outcome Measures
Name Time Method Time from randomisation until death Day 180 Mortality status
Mortality Day 180 Mortality status
Number of days alive and not in ICU Day 28 Mortality status
Number of days alive and not in hospital Day 28 Mortality status
Quality of life assessment Day 180 European Quality of Life 5 Dimensions
Ventilator free days Day 28 Organ support status
Vasopressor free days Day 28 Organ support status
Proportion of patients receiving any renal replacement therapy Day 28 Organ support proportion
Renal replacement therapy free days Day 28 Organ support status
Functional outcomes for patients under 65 years in the work force Day 180 Questions from the Australian Labour Force Survey
Functional outcomes for patients under 65 years and not in the work force and patients 65 years and over living dependently Day 180 World Health Organization Disability Assessment Schedule 2.0
Cause-specific mortality Day 90 Mortality status
Proportion of patients receiving vasopressor support Day 28 Organ support proportion
Proportion of patients with positive blood cultures Day 28 Blood stream infection proportion
Proportion of patients requiring intravenous antimicrobials Day 28 Patients requiring intravenous antimicrobials
Functional outcomes for patients 65 years and over living independently Day 180 Adelaide Activities Profile
Trial Locations
- Locations (46)
Gosford Hospital
🇦🇺Gosford, New South Wales, Australia
Canberra Hospital
🇦🇺Canberra, Australian Capital Territory, Australia
Royal Brisbane and Women's Hospital
🇦🇺Brisbane, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Brisbane, Queensland, Australia
Logan Hospital
🇦🇺Brisbane, Queensland, Australia
Monash Health Dandenong Hospital
🇦🇺Melbourne, Victoria, Australia
Bunbury Hospital
🇦🇺Bunbury, Western Australia, Australia
North Shore Hospital
🇳🇿Auckland, New Zealand
Auckland City Hospital Department of Critical Care Medicine
🇳🇿Auckland, New Zealand
Auckland City Hospital Cardiovascular Intensive Care Unit
🇳🇿Auckland, New Zealand
Middlemore Hospital
🇳🇿Auckland, New Zealand
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Waikato Hospital
🇳🇿Hamilton, New Zealand
Hutt Valley Hospital
🇳🇿Lower Hutt, New Zealand
Hawkes Bay Fallen Soldiers Memorial Hospital
🇳🇿Hastings, New Zealand
Nelson Hospital
🇳🇿Nelson, New Zealand
Rotorua Hospital
🇳🇿Rotorua, New Zealand
Tauranga Hospital
🇳🇿Tauranga, New Zealand
Wellington Regional Hospital
🇳🇿Wellington, New Zealand
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Bendigo Hospital
🇦🇺Bendigo, Victoria, Australia
Footscray Hospital
🇦🇺Footscray, Victoria, Australia
Frankston Hosptial
🇦🇺Frankston, Victoria, Australia
University Hosptial Geelong
🇦🇺Geelong, Victoria, Australia
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Sunshine Hospital
🇦🇺Melbourne, Victoria, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
St Vincent's Hospital Melbourne
🇦🇺Melbourne, Victoria, Australia
St Vincent's Hospital Sydney
🇦🇺Sydney, New South Wales, Australia
Royal North Shore Hosptial
🇦🇺Sydney, New South Wales, Australia
Sydney Adventist Hospital
🇦🇺Sydney, New South Wales, Australia
Concord Hospital
🇦🇺Sydney, New South Wales, Australia
Westmead Hospital
🇦🇺Sydney, New South Wales, Australia
Blacktown Hospital
🇦🇺Sydney, New South Wales, Australia
Liverpool Hospital
🇦🇺Sydney, New South Wales, Australia
St George Hospital
🇦🇺Sydney, New South Wales, Australia
Nepean Hospital
🇦🇺Sydney, New South Wales, Australia
Royal Prince Alfred Hospital
🇦🇺Sydney, New South Wales, Australia
Royal Adelaide Hosptial
🇦🇺Adelaide, South Australia, Australia
Queen Elizabeth Hospital
🇦🇺Adelaide, South Australia, Australia
Lyell McEwin
🇦🇺Adelaide, South Australia, Australia
Sir Charles Gairdner Hospital
🇦🇺Perth, Western Australia, Australia
St John of God Hospital Murdoch
🇦🇺Perth, Western Australia, Australia
Fiona Stanley Hospital
🇦🇺Perth, Western Australia, Australia
Toowoomba Hospital
🇦🇺Toowoomba, Queensland, Australia
Launceston General Hospital
🇦🇺Launceston, Tasmania, Australia