Condition category
Nutritional, Metabolic, Endocrine
Date applied
25/03/2009
Date assigned
09/04/2009
Last edited
21/04/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Current research does not provide clear guidance as to whether intravenous nutritional support (where nutrients are infused into the blood stream) is better than gastric tube feeding (where nutrients are infused into the stomach) for critically ill patients. Previous research studies indicate that intravenous nutritional support has the advantage of being more likely to deliver the intended nutrition, but may be more dangerous. The danger, or complications, can result from problems with the devices used to access the vein (e.g. lung puncture and infection from the tube, or cannula, used), and from metabolic effects due to the fact that the nutrients bypass the normal route of absorption. The aim of this study is to compare intravenous nutritional support with gastric tube feeding in adult critically ill patients.

Who can participate?
Critically ill patients aged 18 or over in critical care units

What does the study involve?
Patients are randomly allocated to intravenous nutritional support or gastric tube feeding, thus allowing us to compare their outcomes in terms of survival and also quality of survival. For those receiving intravenous nutritional support, after 5 days they are weaned onto gastric tube feeding. Those receiving gastric tube feeding but who are not achieving adequate nutrition by day 5 are provided with intravenous nutritional support for as long as is necessary.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Intensive Care National Audit & Research Centre (UK)

When is the study starting and how long is it expected to run for?
June 2011 to December 2013

Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK)

Who is the main contact?
Prof Kathy Rowan

Trial website

Contact information

Type

Scientific

Primary contact

Prof Kathy Rowan

ORCID ID

Contact details

ICNARC
Napier House
24 High Holborn
London
WC1V 6AZ
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HTA 07/52/03; 09/0082

Study information

Scientific title

A phase III, open, multicentre, randomised controlled trial comparing the clinical and cost-effectiveness of early nutritional support in critically ill patients via the parenteral versus the enteral route

Acronym

CALORIES

Study hypothesis

Current study hypothesis as of 08/01/2013:
Is parenteral nutrition (PN) the optimal route of early nutritional support for adult critically ill patients, in terms of clinical and cost-effectiveness, when compared with enteral nutrition (EN)?

Previous study hypothesis until 08/01/2013:
Is parenteral nutrition (PN) the optimal route of early nutritional support for adult critically ill patients, in terms of clinical and cost-effectiveness, when compared with enteral tube feeding (ETF)?

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/075203
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0006/51882/PRO-07-52-03.pdf

Ethics approval

Not provided at time of registration

Study design

Phase III open randomised parallel-group multicentre trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Enteral/parenteral feeding

Intervention

Current interventions as of 08/01/2013:
Early PN versus early EN within 36 hours of the date/time of original admission to a critical care unit.

The protocol for PN (intervention):
1. Initial central venous catheter (including peripherally inserted central venous catheter) insertion and positioning should be in accordance with NHS guidelines with a dedicated lumen
2. Standard feed should be obtained from the unit’s usual stock/supplier, used within the licence indication and fall within the following ranges: energy 1365-2540 total kcal bag-1 and nitrogen 7.2-16.0 total kcal bag-1
3. Units should aim to feed patients to a target of 25 kcal kg day-1 within 48-72 hours, using actual body weight
4. Enteral “trickle feeding” is not permitted for the five days (120 hours)

Local practice and polices should be followed for PN and should include provision for:
1. Ensuring that the patient receives a nutritionally complete feed
2. Inclusion of additional micronutrients if clinically indicated, and as prescribed by the clinician/and or dietician in accordance with National Institute of Clinical Excellence (NICE) guidelines. Additions must be made under appropriate pharmaceutically controlled environmental conditions before administration
3. Adjustment of total volume according to fluid balance requirements
4. Monitoring for specific nutritional-related complications
5. Regular review of patients for their ongoing nutritional support needs
6. Energy requirements for those in extreme BMI categories (e.g. <18.5 and >30kg/m2)

The protocol for EN (control):
1. Initial nasogastric/nasojejunal tube insertion and positioning in accordance with National Patient Safety Agency (NPSA) guidelines
2. Standard feed should be obtained from the unit’s usual stock/supplier, used within the licence indication and fall within the following ranges: energy 1365-2540 total kcal day-1 and nitrogen 7.2-16.0 total kcal day-1
3. Units should aim to feed patients to a target of 25 kcal kg day-1 within 48-72 hours, using actual body weight

Local practice and polices should be followed for EN and should include provision for:
1. Ensuring that the patient receives a nutritionally complete feed
2. Adjustment of total volume according to fluid balance requirements
3. Monitoring for specific nutritional-related complications
4. Regular review of patients for their ongoing nutritional support needs
5. Energy requirements for those in extreme BMI categories (e.g. <18.5 and >30kg/m2)

Both protocols will be followed for five days (120 hours), unless the patient transitions to exclusive oral feeding or is discharged from the critical care unit before this time. Patients may start oral feeding if clinically indicated during the five days.


Previous interventions until 08/01/2013:
Planned interventions:
Early PN versus early ETF within 24 hours but no later than 36 hours after admission.

CALORIES PN protocol will cover:
1. Initial central line (jugular/subclavian) insertion/positioning according to NHS Guidelines with dedicated lumen
2. Standard feed (provided free-of-charge from major manufacturers) with lipid calories (30-60%), nitrogen (0.14 - 0.20 g/kg) and non-nitrogen energy requirement estimated using a suitably adjusted Schofield equation plus standard addition of vitamins, trace elements and electrolyte concentrations according to clinical requirements
3. Intravenous glutamine at 20 g/day (note: standard enteral feed preparations based on casein protein typically contain approximately 10% glutamine and 10% glutamate and further supplementation of ETF with glutamine has not been shown to be beneficial)
4. Total volume adjusted according to fluid balance requirements
5. Starter regimens at 25 - 50% (for day one) and 35 - 65% (for day two) of intended final prescription may be used for those considered at risk of refeeding syndrome
6. Likely maximum delivery in five days
7. Frequency of measurement for specific nutritional-related complications e.g., biochemistry tests

CALORIES ETF protocol will cover:
1. Initial nasogastric tube insertion/positioning according to NPSA Guidelines
2. Isocaloric (1 kcal/ml) standard feed with/without fibre (more concentrated will be permitted if required for fluid balance)
3. Commencement rate and target rates to achieve goal (cal/kg) for objective weight (or estimated weight where objective weight not available)
4. Time period over which goal is to be achieved
5. Nutritional intake of 25 kcal/kg/day
6. Likely maximum delivery in five days
7. Frequency of measurement of aspirates
8. Patient positioning
9. Frequency of measurement for specific nutritional-related complications e.g., diarrhoea

CALORIES will not dictate the use of one ETF protocol and one PN protocol but will review all ETF and PN protocols in use by participating units and ensure that those used by participating units fall within common boundaries. There will be no restriction to products from a single manufacturer. Both, however, will be limited to an agreed range of products fulfilling the criteria. Criteria for will be based on recommendations from the Guidelines of the Canadian Society for Clinical Nutrition for artificial nutritional support in critical care. Both protocols will be based on current standard protocols in use in critical care units in the NHS informed by clinical consensus and literature review.

Proposed duration of intervention:
The PN and ETF protocols will be followed for five days unless the patient transitions to oral feeding beforehand. Patients will be reviewed regularly to enable re-instigation of oral feeding, when appropriate. Crossovers will only be those patients going from ETF to PN or PN to ETF within five days.

Intervention type

Other

Phase

Phase III

Drug names

Primary outcome measures

Current primary outcome measures as of 08/01/2013:
1. To estimate the effect of early (defined as within 36 hours of the date/time of original critical care unit admission) nutritional support via the parenteral route (PN) compared with the enteral route (EN) on mortality at 30 days
2. To estimate the incremental cost-effectiveness of early PN compared with EN at one year

Previous primary outcome measures until 08/01/2013:
30-day all cause mortality and cost-effectiveness at one year.

Secondary outcome measures

Current secondary outcome measures as of 08/10/2013:
To compare PN with EN for:
1. Duration of specific and overall organ support in the critical care unit
2. Infectious and non-infectious complications in the critical care unit
3. Duration of critical care unit and acute hospital length of stay
4. Mortality at discharge from the critical care unit and from hospital
5. Mortality at 90 days and at one year
6. Nutritional and health-related quality of life at 90 days and at one year
7. Resource use and costs at 90 days and at one year
8. Estimated lifetime incremental cost-effectiveness

Previous secondary outcome measures until 08/10/2013:
1. Duration of specific and overall organ support
2. Infectious and non-infectious complications in the critical care unit
3. Duration of critical care unit and acute hospital length of stay
4. Mortality at discharge from the critical care unit and hospital
5. Mortality between 90 days and one year
6. Nutritional and health-related quality of life at 90 days and at one year
7. Resource use and costs at 90 days and one year

Overall trial start date

17/06/2011

Overall trial end date

31/12/2013

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 08/01/2013:
Patients who either on, or soon after admission (but within a timeframe to consent/obtain agreement, randomise and start nutritional support within 36 hours of the date/time of original admission to a critical care unit) are:
1. Adult (defined as age 18 years or over)
2. An unplanned admission (including planned admissions becoming unplanned e.g. unexpected post-operative complications)
3. Expected to receive nutritional support for two or more days in the unit
4. Not planned to be discharged within three days (defined by clinical judgment) from the unit

Previous inclusion criteria until 08/01/2013:
1. Male and female adults (defined as age 18 years or over)
2. Unplanned admission (defined as per the Critical Care Minimum Data Set [CCMDS]
3. Original critical care unit admission (defined as not transferred in from another critical care unit/bed)
4. Not planned to discharge within three days (defined by clinical judgment)
5. Not expected to receive oral feeding within two days

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

2,400

Participant exclusion criteria

Current exclusion criteria as of 08/01/2013:
1. Patients who have been in a critical care unit for more than 36 hours (i.e. from the date/time of original admission to a critical care unit)
2. Patients previously randomised into CALORIES
3. Patients with pre-existing contraindications to PN or EN
4. Patients who have received PN or EN within the last seven days
5. Patients admitted with a percutaneous endoscopic gastrostomy, percutaneous endoscopic jejunostomy, needle/surgical jejunostomy or nasojejunal tube in situ
6. Patients admitted to the critical care unit for treatment of thermal injury (burns)
7. Patients admitted to the critical care unit for palliative care
8. Patients whose expected stay in the UK is less than six months
9. Women who are pregnant

Previous exclusion criteria until 08/01/2013:
1. Pre-existing contraindication to ETF or PN
2. Pregnant women
3. People whose expected stay in the UK is less than six months
4. Patients admitted to the unit for treatment of thermal injury (burns)
5. Patients admitted to the unit for palliative care
6. Patients with percutaneous endoscopic gastrostomy (PEG), percutaneous endoscopic jejunostomy (PEJ) or needle/surgical jejunostomy (JEJ)

Recruitment start date

17/06/2011

Recruitment end date

31/12/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Intensive Care National Audit & Research Centre
London
WC1V 6AZ
United Kingdom

Sponsor information

Organisation

Intensive Care National Audit & Research Centre (ICNARC) (UK)

Sponsor details

Napier House
24 High Holborn
London
WC1V 6AZ
United Kingdom

Sponsor type

Research organisation

Website

http://www.icnarc.org

Funders

Funder type

Government

Funder name

NIHR Health Technology Assessment Programme - HTA (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25271389
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/27089843

Publication citations

  1. Results

    Harvey SE, Parrott F, Harrison DA, Bear DE, Segaran E, Beale R, Bellingan G, Leonard R, Mythen MG, Rowan KM, , Trial of the route of early nutritional support in critically ill adults., N. Engl. J. Med., 2014, 371, 18, 1673-1684, doi: 10.1056/NEJMoa1409860.

  2. Results

    Harvey SE, Parrott F, Harrison DA, Sadique MZ, Grieve RD, Canter RR, McLennan BK, Tan JC, Bear DE, Segaran E, Beale R, Bellingan G, Leonard R, Mythen MG, Rowan KM, A multicentre, randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of early nutritional support via the parenteral versus the enteral route in critically ill patients (CALORIES), Health Technol Assess, 2016 , 20, 28, 1-144, doi: 10.3310/hta20280.

Additional files

Editorial Notes

21/04/2016: Plain English summary and publication reference added. Please note that as of 08/01/2013, the following changes were made to the record: 1. The public title was previously 'Clinical and cost-effectiveness of early parenteral compared with early enteral nutritional support in critically ill patients study '. 2. The scientific title was previously 'Clinical and cost-effectiveness of early parenteral compared with early enteral nutritional support in critically ill patients: a phase III open randomised parallel-group multicentre trial'. 3. The overall trial start date was updated from 01/12/2009 to 17/06/2011. 4. The overall trial end date was updated from 08/12/2012 to 31/12/2013.