Clinical trial NCT03292237: Intensive Nutrition in Critically Ill Adults
Official title: Intensive Nutrition Therapy Compared to Usual Care in Critically Ill Adults: A Randomised Pilot Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Critical Illness
Critically Ill
Keywords: Energy
Nutrition
Critical illness
Parenteral nutrition
Intensive care unit
Ward
Randomised Controlled Trial
Intensive Nutrition
Lead sponsor: Australian and New Zealand Intensive Care Research Centre
Sponsor class: OTHER
Collaborators: name: Baxter Healthcare Corporation
First posted: 2017-09-25
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multicentre, prospective, parallel, randomised controlled trial
Primary purpose: SUPPORTIVE_CARE

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.

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:

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

Eligibility criteria: 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

Primary outcomes:
measure: Daily energy delivered from nutrition therapy
timeFrame: Day 28
Secondary outcomes:
measure: Nutrition intake
timeFrame: Day 28
measure: Duration hospital stay
timeFrame: Day 28
measure: Ventilator Free Days
timeFrame: Day 28
measure: Total blood stream infection rate
timeFrame: Day 28
Other outcomes:
measure: Duration of ICU stay
timeFrame: Day 28
measure: Duration of Mechanical Ventilation
timeFrame: Day 28
measure: ICU mobility scale
timeFrame: Day 28
measure: Mortality
timeFrame: Day 28
measure: Blood stream infections
timeFrame: Day 28
measure: Weight
timeFrame: Day 28
measure: Frailty
timeFrame: 90 days
measure: European Quality Of Life 5 Dimensions 5 Level (EQ5D-5L)
timeFrame: 90 days
measure: World Health Organization Disability Assessment Schedule 2.0 (WHODAS)
timeFrame: 90 days
measure: European Quality Of Life 5 Dimensions 5 Level (EQ5D-5L)
timeFrame: 180 days
measure: World Health Organization Disability Assessment Schedule 2.0 (WHODAS)
timeFrame: 180 days
measure: Cost per quality adjusted life year
timeFrame: 180 days
measure: Cost per life year gained
timeFrame: 180 days
measure: Frailty
timeFrame: 180 dyas
Locations:
city: Blacktown
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Darwin
country: Australia
facility: Royal Darwin Hospital
state: Northern Territory
city: Brisbane
country: Australia
facility: Prince Charles Hospital
state: Queensland
city: Redcliffe
country: Australia
facility: Redcliffe Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin
state: South Australia
city: Woodville South
country: Australia
facility: Queen Elizabeth Hospital
state: South Australia
city: Ballarat
country: Australia
facility: Ballarat Hospital
state: Victoria
city: Bendigo
country: Australia
facility: Bendigo Hospital
state: Victoria
city: Epping
country: Australia
facility: Northern Hospital
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital - Peninsula Health
state: Victoria
city: Geelong
country: Australia
facility: Geelong Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Epworth Richmond
state: Victoria
city: Melbourne
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Auckland
country: New Zealand
facility: Auckland City Hospital CVICU
city: Auckland
country: New Zealand
facility: Middlemore Hospital
Study officials:
affiliation: ANZIC-RC
name: Emma Ridley, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ridley EJ, Bailey M, Chapman M, Chapple LS, Deane AM, Hodgson C, King VL, Marshall A, Miller EG, McGuinness SP, Parke R, Udy AA; the Australian and New Zealand Intensive Care Society Clinical Trials Group; Australian and New Zealand Intensive Care Society Clinical Trials Group. Protocol summary and statistical analysis plan for Intensive Nutrition Therapy comparEd to usual care iN criTically ill adults (INTENT): a phase II randomised controlled trial. BMJ Open. 2022 Mar 8;12(3):e050153. doi: 10.1136/bmjopen-2021-050153.
citation: Ridley EJ. Parenteral nutrition in critical illness: total, supplemental or never? Curr Opin Clin Nutr Metab Care. 2021 Mar 1;24(2):176-182. doi: 10.1097/MCO.0000000000000719.
citation: Ridley EJ, Parke RL, Davies AR, Bailey M, Hodgson C, Deane AM, McGuinness S, Cooper DJ. What Happens to Nutrition Intake in the Post-Intensive Care Unit Hospitalization Period? An Observational Cohort Study in Critically Ill Adults. JPEN J Parenter Enteral Nutr. 2019 Jan;43(1):88-95. doi: 10.1002/jpen.1196. Epub 2018 Jun 20.