Intensive Nutrition in Critically Ill Adults

Critical Illness Clinical Trial

— INTENT  

Official title:

Intensive Nutrition Therapy Compared to Usual Care in Critically Ill Adults: A Randomised Pilot Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03292237
• Other study ID #: ANZIC-RC/ER001
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 15, 2018
• Est. completion date: December 31, 2023

Study information

• Verified date: February 2023
• Source: Australian and New Zealand Intensive Care Research Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 240
• Est. completion date: December 31, 2023
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria

Patients in intensive care who meet all of the following will be eligible:

1. Admitted to intensive care between 72 hours and 120 hours

2. Receiving invasive ventilator support

3. At least 18 years of age

4. Have central venous access suitable for PN solution administration

5. Have 1 or more organ system failure (respiratory, cardiovascular or renal) related to

their acute illness defined as:

• PaO2/FiO2 = 300 mmHg
• Currently on 1 or more continuous inotrope/vasopressor infusion which were

started at least 4 hours ago at a minimum dose of:

1. Noradrenaline = 0.1mcg/kg/min

2. Adrenaline = 0.1 mcg/kg/min

3. Any dose of vasopressin

4. Milrinone > 0.1 mcg/kg/min

• Renal dysfunction defined as:

1. Serum creatinine 2.0-2.9 times baseline OR

2. Urine output 0.5ml/kg/hr for = 12 hours OR

3. Currently receiving renal replacement therapy

• Currently has an intracranial pressure monitor or ventricular drain in situ Exclusion criteria

Patients will be excluded if:

• Both EN and PN cannot be delivered at enrolment (i.e. either an enteral tube or a central venous catheter cannot be placed or clinicians feel that EN or PN cannot be safely administered due to any other reason)
• Currently receiving PN
• Clinician believes a specific parenteral formula is indicated
• Death is imminent in the next 96 hours
• There is a current treatment limitation in place or the patient is unlikely to survive to 6 months due to underlying/chronic illness
• More than 80% of energy requirements have been satisfactorily delivered via the enteral route in the last 24 hours
• Dialysis dependent chronic renal failure
• Suspected or known pregnancy
• Product contraindication
• The treating clinician does not believe the study to be in the best interest of the patient

Related Conditions & MeSH terms

• Critical Illness
• Critically Ill

Intervention

Dietary Supplement:
• Supplemental parenteral nutrition
Supplemental parenteral nutrition OLIMEL N12E (Baxter Healthcare Corporation)

Locations

Country	Name	City	State
Australia	Ballarat Hospital	Ballarat	Victoria
Australia	Bendigo Hospital	Bendigo	Victoria
Australia	Blacktown Hospital	Blacktown	New South Wales
Australia	Prince Charles Hospital	Brisbane	Queensland
Australia	Royal Darwin Hospital	Darwin	Northern Territory
Australia	Lyell McEwin	Elizabeth Vale	South Australia
Australia	Northern Hospital	Epping	Victoria
Australia	Frankston Hospital - Peninsula Health	Frankston	Victoria
Australia	Geelong Hospital	Geelong	Victoria
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	Box Hill Hospital	Melbourne	Victoria
Australia	Epworth Richmond	Melbourne	Victoria
Australia	Monash Medical Centre	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Redcliffe Hospital	Redcliffe	Queensland
Australia	Mater Hospital	South Brisbane	Queensland
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Queen Elizabeth Hospital	Woodville South	South Australia
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
New Zealand	Auckland City Hospital CVICU	Auckland
New Zealand	Middlemore Hospital	Auckland

Sponsors (2)

Lead Sponsor	Collaborator
Australian and New Zealand Intensive Care Research Centre	Baxter Healthcare Corporation

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Duration of ICU stay	Duration of ICU stay in survivors and non survivors	Day 28
Other	Duration of Mechanical Ventilation	Duration of Mechanical Ventilation to study day 28 in survivors and non-survivors	Day 28
Other	ICU mobility scale	ICU mobility scale at ICU discharge	Day 28
Other	Mortality	In hospital and 28 day mortality	Day 28
Other	Blood stream infections	Number of blood stream infections to day 28, time to any blood stream infection	Day 28
Other	Weight	Weight at hospital discharge	Day 28
Other	Frailty	Clinical frailty score	90 days
Other	European Quality Of Life 5 Dimensions 5 Level (EQ5D-5L)	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	90 days
Other	World Health Organization Disability Assessment Schedule 2.0 (WHODAS)	WHODAS is a 12 point disability assessment with a raw score range of 0-48. 0 is no disability and 48 being full disability	90 days
Other	European Quality Of Life 5 Dimensions 5 Level (EQ5D-5L)	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	180 days
Other	World Health Organization Disability Assessment Schedule 2.0 (WHODAS)	WHODAS is a 12 point disability assessment with a raw score range of 0-48. 0 is no disability and 48 being full disability	180 days
Other	Cost per quality adjusted life year	Cost per quality adjusted life year (QALY)	180 days
Other	Cost per life year gained	Cost per life year gained (LYG)	180 days
Other	Frailty	Clinical frailty score	180 dyas
Primary	Daily energy delivered from nutrition therapy	Daily energy delivered from nutrition therapy	Day 28
Secondary	Nutrition intake	Daily protein intake, Energy and protein intake by location (ICU and ward)	Day 28
Secondary	Duration hospital stay	Duration of hospital stay in survivors and non-survivors	Day 28
Secondary	Ventilator Free Days	Ventilator Free Days (VFDs) at study day 28	Day 28
Secondary	Total blood stream infection rate	Total blood stream infection rate	Day 28