Condition category
Signs and Symptoms
Date applied
13/03/2007
Date assigned
28/03/2007
Last edited
01/02/2011
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Greet Van den Berghe

ORCID ID

Contact details

Director of the Department of Intensive Care Medicine
Catholic University Leuven University Hospitals
and
Chair of the Division of Acute Medical Sciences
Catholic University Leuven
Herestraat 49
Leuven
3000
Belgium

Additional identifiers

EudraCT number

2007-000169-40

ClinicalTrials.gov number

NCT00512122

Protocol/serial number

EPaNIC 2007.1-2-2; Clinical study no.: S50404

Study information

Scientific title

Acronym

EPaNIC

Study hypothesis

In critically ill patients, a strategy aimed at an early delivery of full caloric support, with a combination of Enteral Nutrition (EN) and Parenteral Nutrition (PN) (in conditions preventing hyperglycemia and overfeeding), results in shorter Intensive Care Unit (ICU) and hospital stay and less morbidity as compared to a strategy using only EN.

Please note that as of 25/05/10 this record has been updated to reflect changes in the protocol between v.1-1-7 and v.1-2-2. All updates can be found in the relevant field with the above update date. Please also note that the anticipated end date of this trial has been extended from 01/05/10 to 01/11/2012. This date includes recruitment, data collection and follow up phases.

Ethics approval

The study protocol and consent forms are approved by the Institutional Review Board of the Catholic University Leuven School of Medicine approved on the 21st March 2007 (ref: ML4190)

Added 25/05/10:
All amendments were approved by the Institutional Review Board of the Catholic University of Leuven School of Medicine. Latest approval date was the 15th of March 15 2010 (ref: ML4190)
The addition of a new study site and conversion to multicentre trial was authorised by the Belgian Federal Agency for Medicine and Health Products on the 12th of January 2010

Study design

Open label prospective randomised controlled parallel group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Critical Illness

Intervention

Written informed consent will be obtained from the patient or the closest family member or legal guardian. The family member or the patient can withdraw from the trial, at any time, without impact on his treatment or penalty. The investigators confirm that this study concerns a condition that directly threatens patient health and that the adult patient not able to give consent suffers from the condition. The experiment is essential to confirm the results from earlier research in patients who could consent or from other research methods.

On admission patients will be randomly assigned to receive EN combined with early PN or only EN. At ICU admission, consecutive patients will be randomly assigned to one of these two treatment groups using blinded envelopes, stratified according to primary diagnostic category on admission.
Paragraph ammended 25/05/10: Upon addition of the new study site, the numbered en sealed envelopes for randomization stratified according to primary diagnostic category on admission were replaced by an identical digital system allowing central randomisation

As initial nutritional support, patients randomised to the ‘EN combined with early PN’ group will receive glucose 20% at 40 ml/hr. EN will be initiated in the evening of the second ICU hospitalisation day, PN will be started the morning of the third ICU hospitalisation day. The amount of PN to be given on any particular day will be the difference between calculated caloric needs and the calories delivered by EN the previous 24 hours. When EN covers 80% of calculated caloric needs PN will be stopped. When the patient is able to eat, the parenteral regimen will be reduced and eventually stopped. Whenever oral (+ enteral) intake is below 50% of calculated caloric needs, the PN will be (re)-started.

As initial nutritional support, patients randomised to the ‘EN only’ group will receive glucose 5% at 40 ml/hr. EN will be initiated on the evening of the second ICU day. From the morning of the third ICU hospitalisation day on, the amount of glucose 5% to be given will be the same as the volume of PN the patient theoretically would require to receive 100% of presumed caloric needs based on the amount of EN delivered the previous 24 hours. When the patient is able to eat, the parenteral regimen (glucose 5%) will be reduced to 50% and eventually stopped. Whenever oral (+ enteral) intake is below 50% of calculated caloric needs, the PN (glucose 5%) will be (re)-started. If these patients would need to stay for more than seven days on the ICU and enteral feeding of at least 80% of the calculated calories is not possible, they will be switched to EN and PN on day eight.

Common strategy for attempting early enteral nutrition in both study arms:
EN will be initiated on the evening of the second ICU day, unless patients are able to eat. The increase of enteral feeding volume and the adaptation of the regimen to pathological conditions will be according to protocol. Trace elements, minerals and vitamins will be administered daily intravenously (IV) to all patients from the day of admission onwards. IV substitution will be stopped in patients receiving at least 1500 ml of EN. All patients will be treated following the intensive insulin therapy schedule – targeting a blood glucose level of 80 - 110 mg/dl – from admission until discharge or oral feeding.

Patients will be weaned from the ventilator according to a standard protocol. End-of-care decisions in patients for whom further intensive care is considered to be futile will be taken in consensus by a group of two senior ICU physicians and the referring specialist, all blinded to study treatment allocation.

Added 25/05/10:
In a subgroup of patients, pathways of inflammation and metabolism and the endocrinological impact of the intervention will be studied in blood samples and in snap-frozen in vivo biopsies of muscle and adipose tissue. Blood and tissue samples from healthy volunteers will serve as references for these exploratory studies. In some patients, radiological evolution of regional muscle and adipose tissue volumes will be evaluated.

Changes to dates of trial as of 30/07/2007:
This trial will start recruitment on the 1st August 2007, and the anticipated end date of this trial has been extended to the 1st November 2010.

Please note that as of 25/05/10 this trial is still in recruitment phase.
The anticipated date of last inclusion is 30/11/2010.
The anticipated date for the collection of last primary endpoints is 01/03/11.
Rehabilitation follow up study will go on until November 2012.

Please not that the last patient in the EPaNIC trial was included on 08/11/2010. The 90 day mortality will be available for all patients on 08/02/2011.

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

The primary outcome measure of this study will be length of stay in ICU and the hospital.

Secondary outcome measures

Current information as of 25/05/10:
1. Death (hospital, ICU and 90 days mortality)
2. The secondary morbidity outcomes will include:
2.1. Days to weaning from mechanical ventilation
2.2. The need for renal replacement therapies
2.3. The presence or absence of new kidney injury during intensive care
2.4. Days of vasopressor or inotropic support
2.5. The presence or absence of signs of ICU liver disease: hyperbilirubinemia (defined as bilirubin level > 3 mg/dl), presence of liversteatosis, sludge
2.6. The need for tracheotomy
2.7. The presence or absence of hyper-inflammation within five days after ICU admission
2.8. Blood lipid profiles and albumin on days one, five, ten, and 15 after admission
2.9. The presence or absence of bacteraemia, ventilator-associated pneumonia and of wound infections
2.10. Episodes of hypoglycaemic events (defined as glycemia less than 40 mg/dl)
2.11. Amount and type of calories delivered
2.12. Muscle strength and rehabilitation
2.13. Presence of clinical and electrophysiological signs of respiratory and peripheral muscle weakness

Initial information at time of registration:
1. Death (hospital and ICU mortality)
2. The secondary morbidity outcomes will include:
2.1. Days to weaning from mechanical ventilation
2.2. The need for renal replacement therapies
2.3. The presence or absence of new kidney injury during intensive care
2.4. Days of vasopressor or inotropic support
2.5. The presence or absence of hyperbilirubinemia and liversteatosis
2.6. The need for tracheotomy
2.7. The presence or absence of hyper-inflammation within five days after ICU admission
2.8. Blood lipid profiles and albumin on days one, five, ten, and 15 after admission
2.9. The presence or absence of bacteraemia, ventilator-associated pneumonia and of wound infections
2.10. Episodes of hypoglycaemic events (defined as glycemia less than 40 mg/dl)
2.11. Amount and type of calories delivered
2.12. Muscle strength and rehabilitation

Overall trial start date

01/05/2007

Overall trial end date

08/02/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients admitted to any of the five intensive care units
2. Older than 18 years
3. Nutritional Risk Screening Score (NRS) score higher or equal to three upon ICU admission

Participant type

Patient

Age group

Adult

Gender

Not Specified

Target number of participants

4640 patients (2320 per arm)

Participant exclusion criteria

1. Patients with a Do Not Resuscitate (DNR) code or moribund at the time of ICU admission
2. Patients already enrolled in another trial
3. Patients transferred from another intensive care unit with an established nutritional therapy
4. Patients suffering from ketoacidotic or hyperosmolar coma on admission
5. Patients with a Body Mass Index (BMI) below 17 kg/m^2
6. Short Bowel Syndrome
7. Patients known to be pregnant or nursing
8. Patients on mechanical ventilation at home
9. NRS score lower than three

Added 25/05/10:
10. Patient readmitted to ICU after randomisation to the EPaNIC trial
11. Patient not critically ill on admission (No clinical indication for central intravenous catheter or patient ready for oral nutrition on admission)

Recruitment start date

01/05/2007

Recruitment end date

08/02/2011

Locations

Countries of recruitment

Belgium

Trial participating centre

Director of the Department of Intensive Care Medicine
Leuven
3000
Belgium

Sponsor information

Organisation

Catholic University Leuven (Katholieke Universiteit Leuven) (Belgium)

Sponsor details

c/o Professor Dr Ir Koenraad Debackere
Managing Director
Leuven Research and Development
Minderbroedersstraat 8A - bus 5105
Leuven
3000
Belgium

Sponsor type

University/education

Website

http://www.kuleuven.ac.be/english/index.htm

Funders

Funder type

Industry

Funder name

Catholic University Leuven (Katholieke Universiteit Leuven) (Belgium)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Research Foundation – Flanders (Fond Wetenschappelijk Onderzoek Vlaanderen [FWO]) (Belgium)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Baxter SAS (France) - unrestricted and non-conditional research grant

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

1. 2011 protocol in http://www.ncbi.nlm.nih.gov/pubmed/21261975

Publication citations

  1. Protocol

    Casaer MP, Hermans G, Wilmer A, Van den Berghe G, Impact of early parenteral nutrition completing enteral nutrition in adult critically ill patients (EPaNIC trial): a study protocol and statistical analysis plan for a randomized controlled trial., Trials, 2011, 12, 21, doi: 10.1186/1745-6215-12-21.

Additional files

Editorial Notes