INTENT: Intensive Nutrition in Critically Ill Adults

Sponsor

Australian and New Zealand Intensive Care Research Centre (Other)

Overall Status

Recruiting

CT.gov ID

NCT03292237

Collaborator

Baxter Healthcare Corporation (Industry)

240

Enrollment

Locations

Arms

49.5

Anticipated Duration (Months)

10.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Critical Illness Critically Ill	Dietary Supplement: Supplemental parenteral nutrition	Phase 2

Detailed 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:

To determine whether the whole hospital nutrition intervention leads to increased amounts of total energy delivered over the period of hospital stay
To determine if the whole hospital nutrition intervention is safe in regards to adverse effects
To determine if the post-ICU nutrition intervention is practically feasible when applied in multiple hospitals, across multiple wards
To measure the clinical outcomes in patients and provide information to assist design of a larger randomised controlled trial

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

multicentre, prospective, parallel, randomised controlled trialmulticentre, prospective, parallel, randomised controlled trial

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

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

Actual Study Start Date :

Oct 15, 2018

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Standard Nutrition Arm 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.
Experimental: Intensive Arm 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.	Dietary Supplement: Supplemental parenteral nutrition Supplemental parenteral nutrition OLIMEL N12E (Baxter Healthcare Corporation)

Arm

Intervention/Treatment

No Intervention: Standard Nutrition Arm

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.

Experimental: Intensive Arm

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.

Dietary Supplement: Supplemental parenteral nutrition

Supplemental parenteral nutrition OLIMEL N12E (Baxter Healthcare Corporation)

Outcome Measures

Primary Outcome Measures

Daily energy delivered from nutrition therapy [Day 28]
Daily energy delivered from nutrition therapy

Secondary Outcome Measures

Nutrition intake [Day 28]
Daily protein intake, Energy and protein intake by location (ICU and ward)
Duration hospital stay [Day 28]
Duration of hospital stay in survivors and non-survivors
Ventilator Free Days [Day 28]
Ventilator Free Days (VFDs) at study day 28
Total blood stream infection rate [Day 28]
Total blood stream infection rate

Other Outcome Measures

Duration of ICU stay [Day 28]
Duration of ICU stay in survivors and non survivors
Duration of Mechanical Ventilation [Day 28]
Duration of Mechanical Ventilation to study day 28 in survivors and non-survivors
ICU mobility scale [Day 28]
ICU mobility scale at ICU discharge
Mortality [Day 28]
In hospital and 28 day mortality
Blood stream infections [Day 28]
Number of blood stream infections to day 28, time to any blood stream infection
Weight [Day 28]
Weight at hospital discharge
Frailty [90 days]
Clinical frailty score
European Quality Of Life 5 Dimensions 5 Level (EQ5D-5L) [90 days]
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
World Health Organization Disability Assessment Schedule 2.0 (WHODAS) [90 days]
WHODAS is a 12 point disability assessment with a raw score range of 0-48. 0 is no disability and 48 being full disability
European Quality Of Life 5 Dimensions 5 Level (EQ5D-5L) [180 days]
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
World Health Organization Disability Assessment Schedule 2.0 (WHODAS) [180 days]
WHODAS is a 12 point disability assessment with a raw score range of 0-48. 0 is no disability and 48 being full disability
Cost per quality adjusted life year [180 days]
Cost per quality adjusted life year (QALY)
Cost per life year gained [180 days]
Cost per life year gained (LYG)
Frailty [180 dyas]
Clinical frailty score

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria

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

Admitted to intensive care between 72 hours and 120 hours
Receiving invasive ventilator support
At least 18 years of age
Have central venous access suitable for PN solution administration
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:

Noradrenaline ≥ 0.1mcg/kg/min
Adrenaline ≥ 0.1 mcg/kg/min
Any dose of vasopressin
Milrinone > 0.1 mcg/kg/min

Renal dysfunction defined as:

Serum creatinine 2.0-2.9 times baseline OR
Urine output 0.5ml/kg/hr for ≥ 12 hours OR
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Blacktown Hospital	Blacktown	New South Wales	Australia	2148
2	Nepean Hospital	Kingswood	New South Wales	Australia	2747
3	Royal Darwin Hospital	Darwin	Northern Territory	Australia	0810
4	Prince Charles Hospital	Brisbane	Queensland	Australia	4032
5	Redcliffe Hospital	Redcliffe	Queensland	Australia	4020
6	Mater Hospital	South Brisbane	Queensland	Australia	4101
7	Gold Coast University Hospital	Southport	Queensland	Australia	4215
8	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
9	Lyell McEwin	Elizabeth Vale	South Australia	Australia	5112
10	Queen Elizabeth Hospital	Woodville South	South Australia	Australia	5011
11	Ballarat Hospital	Ballarat	Victoria	Australia	3350
12	Bendigo Hospital	Bendigo	Victoria	Australia	3550
13	Northern Hospital	Epping	Victoria	Australia	3076
14	Frankston Hospital - Peninsula Health	Frankston	Victoria	Australia	3199
15	Geelong Hospital	Geelong	Victoria	Australia	3220
16	Austin Hospital	Heidelberg	Victoria	Australia	3084
17	The Alfred Hospital	Melbourne	Victoria	Australia	3004
18	Royal Melbourne Hospital	Melbourne	Victoria	Australia	3010
19	Epworth Richmond	Melbourne	Victoria	Australia	3121
20	Box Hill Hospital	Melbourne	Victoria	Australia	3128
21	Monash Medical Centre	Melbourne	Victoria	Australia	3168
22	Auckland City Hospital CVICU	Auckland		New Zealand	1023
23	Middlemore Hospital	Auckland		New Zealand	2025