Impact of Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients

NCT00512122 | Active Not Recruiting Phase 4 DMC

• 4 other identifiers: EPaNIC 2007 1-2-2ISRCTN 76223876EudraCT 2007-000169-40S 50404
• Study Type: interventional
• Target: 4,640
• Locations: 1 country
• Sites: 3

Brief Summary

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 ICU and hospital stay and less morbidity as compared to a strategy using only EN.

Conditions

Critical Illness; Starvation

Keywords

early parenteral nutrition; critical illness; respiratory failure; kidney failure; hepatic failure; muscle strength; rehabilitation; overfeeding; Reduced Oral Intake

Outcome Measures

Primary Outcomes (1)

• Length of stay in ICU and length of stay in the hospital.

  2 years

Secondary Outcomes (14)

• Death (hospital and ICU mortality and 90 days mortality)

  10 years

• Days to weaning from mechanical ventilation

  2 years

• The need for renal replacement therapies

  2 years

• The presence or absence of new kidney injury during intensive care

  2 years

• Days of vasopressor or inotropic support

  2 years

Study Arms (2)

EN only

EXPERIMENTAL

Withholding PN during the first week of ICU stay

Other: Withholding PN during the first week of ICU stay

EN plus early PN

ACTIVE COMPARATOR

Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E Parenteral nutrition targeted at covering calculated needs together with the enteral nutrition intake that is achieved

Drug: Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E

Interventions

Withholding PN during the first week of ICU stay OTHER

Patients in this arm will receive exclusively enteral nutrition. If enteral nutrition is insufficient after the seventh day of ICU stay, parenteral nutrition will be started.

EN only

Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E DRUG

PN will be started the morning of the third ICU hospitalisation day. The amount of PN to be given will be calculated to cover the caloric needs of the patient, based on the enteral energy intake the previous 24 hours.

Also known as: Parenteral nutrition ATC code B05BA10

EN plus early PN

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients admitted to any of the five intensive care units
• Older than 18 years
• Nutritional risk screening score (NRS) higher or equal to three upon ICU admission

You may not qualify if:

• Patients with a do not resuscitate (DNR) code or moribund at the time of ICU admission
• Patients already enrolled in another trial
• Patients transferred from another intensive care unit with an established nutritional therapy
• Patients suffering from ketoacidotic or hyperosmolar coma on admission
• Patients with a body mass index (BMI) below 17 kg/m\^2
• Short bowel syndrome
• Patients known to be pregnant or nursing
• Patients on mechanical ventilation at home
• NRS score lower than three
• Patient readmitted to ICU after randomization to the EPaNIC trial.
• Patient not critically ill on admission. (No clinical indication for central intravenous catheter or patient ready for oral nutrition on admission.)

Sponsors & Collaborators

• KU Leuven: lead
• Fund for Scientific Research, Flanders, Belgium: collaborator
• Baxter Healthcare Corporation: collaborator

Study Sites (3)

Surgical Intensive Care Unit Regional Hospital Jessa

Hasselt, 3500, Belgium

Location

Medical Intensive Care Unit

Leuven, 3000, Belgium

Location

Surgical Intensive Care Unit, Catholic University Leuven University Hospitals

Leuven, 3000, Belgium

Location

Related Publications (22)

• van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001 Nov 8;345(19):1359-67. doi: 10.1056/NEJMoa011300.

  PMID: 11794168 BACKGROUND

• Uzun Ayar C, Guiza F, Derese I, Pauwels L, Vander Perre S, Pintelon I, Casaer M, Van Aerde N, Hermans G, Derde S, Kreiss L, Van den Berghe G, Vanhorebeek I. Altered muscle transcriptome as molecular basis of long-term muscle weakness in survivors from critical illness. Intensive Care Med. 2025 Jun;51(6):1062-1077. doi: 10.1007/s00134-025-07949-3. Epub 2025 Jun 10.

  PMID: 40493222 DERIVED

• Casaer MP, Stragier H, Hermans G, Hendrickx A, Wouters PJ, Dubois J, Guiza F, Van den Berghe G, Gunst J. Impact of withholding early parenteral nutrition on 2-year mortality and functional outcome in critically ill adults. Intensive Care Med. 2024 Oct;50(10):1593-1602. doi: 10.1007/s00134-024-07546-w. Epub 2024 Jul 17.

  PMID: 39017697 DERIVED

• Van Dyck L, Guiza F, Derese I, Pauwels L, Casaer MP, Hermans G, Wouters PJ, Van den Berghe G, Vanhorebeek I. DNA methylation alterations in muscle of critically ill patients. J Cachexia Sarcopenia Muscle. 2022 Jun;13(3):1731-1740. doi: 10.1002/jcsm.12970. Epub 2022 Mar 11.

  PMID: 35274472 DERIVED

• Vanhorebeek I, Derese I, Gunst J, Wouters PJ, Hermans G, Van den Berghe G. Persisting neuroendocrine abnormalities and their association with physical impairment 5 years after critical illness. Crit Care. 2021 Dec 16;25(1):430. doi: 10.1186/s13054-021-03858-1.

  PMID: 34915907 DERIVED

• Ingels C, Langouche L, Dubois J, Derese I, Vander Perre S, Wouters PJ, Gunst J, Casaer M, Guiza F, Vanhorebeek I, Van den Berghe G. C-reactive protein rise in response to macronutrient deficit early in critical illness: sign of inflammation or mediator of infection prevention and recovery. Intensive Care Med. 2022 Jan;48(1):25-35. doi: 10.1007/s00134-021-06565-1. Epub 2021 Nov 24.

  PMID: 34816288 DERIVED

• Van Aerde N, Meersseman P, Debaveye Y, Wilmer A, Gunst J, Casaer MP, Wauters J, Wouters PJ, Gosselink R, Van den Berghe G, Hermans G. Five-year outcome of respiratory muscle weakness at intensive care unit discharge: secondary analysis of a prospective cohort study. Thorax. 2021 Jun;76(6):561-567. doi: 10.1136/thoraxjnl-2020-216720. Epub 2021 Mar 12.

  PMID: 33712505 DERIVED

• Van Dyck L, Gunst J, Casaer MP, Peeters B, Derese I, Wouters PJ, de Zegher F, Vanhorebeek I, Van den Berghe G. The clinical potential of GDF15 as a "ready-to-feed indicator" for critically ill adults. Crit Care. 2020 Sep 14;24(1):557. doi: 10.1186/s13054-020-03254-1.

  PMID: 32928255 DERIVED

• Van Aerde N, Meersseman P, Debaveye Y, Wilmer A, Gunst J, Casaer MP, Bruyninckx F, Wouters PJ, Gosselink R, Van den Berghe G, Hermans G. Five-year impact of ICU-acquired neuromuscular complications: a prospective, observational study. Intensive Care Med. 2020 Jun;46(6):1184-1193. doi: 10.1007/s00134-020-05927-5. Epub 2020 Jan 22.

  PMID: 31970446 DERIVED

• Hermans G, Van Aerde N, Meersseman P, Van Mechelen H, Debaveye Y, Wilmer A, Gunst J, Casaer MP, Dubois J, Wouters P, Gosselink R, Van den Berghe G. Five-year mortality and morbidity impact of prolonged versus brief ICU stay: a propensity score matched cohort study. Thorax. 2019 Nov;74(11):1037-1045. doi: 10.1136/thoraxjnl-2018-213020. Epub 2019 Sep 3.

  PMID: 31481633 DERIVED

• Van Dyck L, Derese I, Vander Perre S, Wouters PJ, Casaer MP, Hermans G, Van den Berghe G, Vanhorebeek I. The GH Axis in Relation to Accepting an Early Macronutrient Deficit and Outcome of Critically Ill Patients. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5507-5518. doi: 10.1210/jc.2019-00842.

  PMID: 31361307 DERIVED

• Thiessen SE, Derde S, Derese I, Dufour T, Vega CA, Langouche L, Goossens C, Peersman N, Vermeersch P, Vander Perre S, Holst JJ, Wouters PJ, Vanhorebeek I, Van den Berghe G. Role of Glucagon in Catabolism and Muscle Wasting of Critical Illness and Modulation by Nutrition. Am J Respir Crit Care Med. 2017 Nov 1;196(9):1131-1143. doi: 10.1164/rccm.201702-0354OC.

  PMID: 28475354 DERIVED

• Flechet M, Guiza F, Schetz M, Wouters P, Vanhorebeek I, Derese I, Gunst J, Spriet I, Casaer M, Van den Berghe G, Meyfroidt G. AKIpredictor, an online prognostic calculator for acute kidney injury in adult critically ill patients: development, validation and comparison to serum neutrophil gelatinase-associated lipocalin. Intensive Care Med. 2017 Jun;43(6):764-773. doi: 10.1007/s00134-017-4678-3. Epub 2017 Jan 27.

  PMID: 28130688 DERIVED

• Hermans G, Van Mechelen H, Bruyninckx F, Vanhullebusch T, Clerckx B, Meersseman P, Debaveye Y, Casaer MP, Wilmer A, Wouters PJ, Vanhorebeek I, Gosselink R, Van den Berghe G. Predictive value for weakness and 1-year mortality of screening electrophysiology tests in the ICU. Intensive Care Med. 2015 Dec;41(12):2138-48. doi: 10.1007/s00134-015-3979-7. Epub 2015 Aug 13.

  PMID: 26266842 DERIVED

• Hermans G, Van Mechelen H, Clerckx B, Vanhullebusch T, Mesotten D, Wilmer A, Casaer MP, Meersseman P, Debaveye Y, Van Cromphaut S, Wouters PJ, Gosselink R, Van den Berghe G. Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis. Am J Respir Crit Care Med. 2014 Aug 15;190(4):410-20. doi: 10.1164/rccm.201312-2257OC.

  PMID: 24825371 DERIVED

• Hermans G, Casaer MP, Clerckx B, Guiza F, Vanhullebusch T, Derde S, Meersseman P, Derese I, Mesotten D, Wouters PJ, Van Cromphaut S, Debaveye Y, Gosselink R, Gunst J, Wilmer A, Van den Berghe G, Vanhorebeek I. Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial. Lancet Respir Med. 2013 Oct;1(8):621-629. doi: 10.1016/S2213-2600(13)70183-8. Epub 2013 Sep 10.

  PMID: 24461665 DERIVED

• Boonen E, Vervenne H, Meersseman P, Andrew R, Mortier L, Declercq PE, Vanwijngaerden YM, Spriet I, Wouters PJ, Vander Perre S, Langouche L, Vanhorebeek I, Walker BR, Van den Berghe G. Reduced cortisol metabolism during critical illness. N Engl J Med. 2013 Apr 18;368(16):1477-88. doi: 10.1056/NEJMoa1214969. Epub 2013 Mar 19.

  PMID: 23506003 DERIVED

• Langouche L, Vander Perre S, Marques M, Boelen A, Wouters PJ, Casaer MP, Van den Berghe G. Impact of early nutrient restriction during critical illness on the nonthyroidal illness syndrome and its relation with outcome: a randomized, controlled clinical study. J Clin Endocrinol Metab. 2013 Mar;98(3):1006-13. doi: 10.1210/jc.2012-2809. Epub 2013 Jan 24.

  PMID: 23348400 DERIVED

• Casaer MP, Wilmer A, Hermans G, Wouters PJ, Mesotten D, Van den Berghe G. Role of disease and macronutrient dose in the randomized controlled EPaNIC trial: a post hoc analysis. Am J Respir Crit Care Med. 2013 Feb 1;187(3):247-55. doi: 10.1164/rccm.201206-0999OC. Epub 2012 Nov 29.

  PMID: 23204255 DERIVED

• Vanderheyden S, Casaer MP, Kesteloot K, Simoens S, De Rijdt T, Peers G, Wouters PJ, Coenegrachts J, Grieten T, Polders K, Maes A, Wilmer A, Dubois J, Van den Berghe G, Mesotten D. Early versus late parenteral nutrition in ICU patients: cost analysis of the EPaNIC trial. Crit Care. 2012 May 25;16(3):R96. doi: 10.1186/cc11361.

  PMID: 22632574 DERIVED

• Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut S, Ingels C, Meersseman P, Muller J, Vlasselaers D, Debaveye Y, Desmet L, Dubois J, Van Assche A, Vanderheyden S, Wilmer A, Van den Berghe G. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011 Aug 11;365(6):506-17. doi: 10.1056/NEJMoa1102662. Epub 2011 Jun 29.

  PMID: 21714640 DERIVED

• 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 Jan 24;12:21. doi: 10.1186/1745-6215-12-21.

  PMID: 21261975 DERIVED

Related Links

• Katholieke Universiteit Leuven Homepage
• Casaer et al.: 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.
• Casaer MP et al.: Early versus late parenteral nutrition in critically ill adults

MeSH Terms

Conditions

Critical Illness; Starvation; Hyperphagia; Respiratory Insufficiency; Renal Insufficiency; Liver Failure

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Respiration Disorders; Respiratory Tract Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Officials

• Greet Van den Berghe, MD Ph D

  Director of the Department of Intensive Care Medicine Catholic Univeresity Leuven

  STUDY DIRECTOR

• Michaël P Casaer, MD

  Department of Intensive Care Medicine Catholic University Leuven

  PRINCIPAL INVESTIGATOR

• Alexander P Wilmer, MD Ph D

  Department of Medicine Catholic University Leuven

  PRINCIPAL INVESTIGATOR

• Jasperina Dubois, MD

  Surgical Intensive Care Unit Regional Hospital Jessa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: All outcome adjudicators were unaware of study-group assignments
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: July 31, 2007
• First Posted: August 7, 2007
• Study Start: August 1, 2007
• Primary Completion: February 1, 2011
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 12, 2024

Record last verified: 2024-02

Locations

BE (3)