Early Versus Late Parenteral Nutrition in the Pediatric Intensive Care Unit

NCT01536275 | Active Not Recruiting DMC

• 5 other identifiers: PEPaNIC2012-000811-10ML8052NL38772.000.12IWT-TBM 110685
• Study Type: interventional
• Target: 1,440
• Locations: 3 countries
• Sites: 3

Brief Summary

In the PEPaNIC trial it is investigated whether withholding parenteral nutrition during the first week in critically ill children is beneficial, compared to the current standard of the early start of parenteral nutrition.

Conditions

Critical Illness; Children

Keywords

critical illness; children; nutrition; metabolism

Outcome Measures

Primary Outcomes (2)

• Incidence of new infection during ICU stay

  during ICU stay and up to 90 days post-randomization

• Duration of ICU dependency (crude stay days and time to alive discharge from ICU)

  during ICU stay and up to 90 days post-randomization

Secondary Outcomes (15)

• Mortality

  during ICU stay, hospital stay and up to 90 days post-randomization

• Time to alive discharge from hospital

  during hospital stay and up to 90 days post-randomization

• Incidence of hypoglycaemia during ICU stay

  during the intervention window up to day 8 post-randomization

• Time to final weaning from mechanical respiratory support

  during ICU stay and up to 90 days post-randomization

• Incidence of liver dysfunction during ICU stay

  during ICU stay and up 90 days post-randomization

Study Arms (2)

Early parenteral nutrition

NO INTERVENTION

Parenteral nutrition supplements insufficient enteral nutrition from admission to ICU according to the current standard of care per center

Late parenteral nutrition

EXPERIMENTAL

Parenteral nutrition will be withheld during the first 7 days of ICU stay

Other: Late parenteral nutrition

Interventions

Late parenteral nutrition OTHER

Withholding parenteral nutrition during the first 7 days of ICU stay

Also known as: Late PN

Late parenteral nutrition

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• All patients admitted to the PICU with a STRONGkids score of 2 points or more upon ICU admission

You may not qualify if:

• Age of 17 years or older
• Patients with a DNR code at the time of ICU admission.
• Patients expected to die within 12 hours (=moribund patients).
• Patient readmitted to ICU after randomization to the PEPaNIC trial, more than 48 hours after the initial discharge
• Patients transferred from another paediatric intensive care after a stay of more than 7 days
• Patients suffering from ketoacidotic or hyperosmolar coma on admission.
• Patients suffering from Short Bowel Syndrome on home PN or other conditions that require home PN
• Patients suspicious or established inborn metabolic diseases requiring specific diet
• STRONGkids score lower than 2 on ICU admission.
• Premature Newborns ( 37 weeks gestational age upon admission in the PICU)

Sponsors & Collaborators

• KU Leuven: lead
• Sophia Kindergeneeskunde: collaborator
• Stollery Children's Hospital: collaborator

Study Sites (3)

Dept Intensive Care Medicine

Leuven, 3000, Belgium

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Erasmus MC Sophia Kinderziekenhuis

Rotterdam, 3015, Netherlands

Location

Related Publications (19)

• 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 BACKGROUND

• Vlasselaers D, Milants I, Desmet L, Wouters PJ, Vanhorebeek I, van den Heuvel I, Mesotten D, Casaer MP, Meyfroidt G, Ingels C, Muller J, Van Cromphaut S, Schetz M, Van den Berghe G. Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study. Lancet. 2009 Feb 14;373(9663):547-56. doi: 10.1016/S0140-6736(09)60044-1. Epub 2009 Jan 26.

  PMID: 19176240 BACKGROUND

• Nakano FK, Dulfer K, Vanhorebeek I, Wouters PJ, Verbruggen SC, Joosten KF, Guiza Grandas F, Vens C, Van den Berghe G. Predicting adverse long-term neurocognitive outcomes after pediatric intensive care unit admission. Comput Methods Programs Biomed. 2024 Jun;250:108166. doi: 10.1016/j.cmpb.2024.108166. Epub 2024 Apr 10.

  PMID: 38614026 DERIVED

• Veldscholte K, Hulst JM, Eveleens RD, de Jonge RCJ, de Koning BAE, van den Berg SAA, van der Wal R, Ruijter GJG, Rizopoulos D, Vanhorebeek I, Gunst J, Casaer M, Van den Berghe G, Joosten KFM, Verbruggen SCAT. Gastrointestinal Biomarkers and Their Association with Feeding in the First Five Days of Pediatric Critical Illness. J Pediatr Gastroenterol Nutr. 2023 Dec 1;77(6):811-818. doi: 10.1097/MPG.0000000000003950. Epub 2023 Sep 20.

  PMID: 37728917 DERIVED

• Verlinden I, Coppens G, Vanhorebeek I, Guiza F, Derese I, Wouters PJ, Joosten KF, Verbruggen SC, Van den Berghe G. Long-term impact of paediatric critical illness on the difference between epigenetic and chronological age in relation to physical growth. Clin Epigenetics. 2023 Jan 14;15(1):8. doi: 10.1186/s13148-023-01424-w.

  PMID: 36639798 DERIVED

• Coppens G, Vanhorebeek I, Verlinden I, Derese I, Wouters PJ, Joosten KF, Verbruggen SC, Guiza F, Van den Berghe G. Assessment of aberrant DNA methylation two years after paediatric critical illness: a pre-planned secondary analysis of the international PEPaNIC trial. Epigenetics. 2023 Dec;18(1):2146966. doi: 10.1080/15592294.2022.2146966. Epub 2022 Nov 16.

  PMID: 36384393 DERIVED

• Vanhorebeek I, Jacobs A, Mebis L, Dulfer K, Eveleens R, Van Cleemput H, Wouters PJ, Verlinden I, Joosten K, Verbruggen S, Van den Berghe G. Impact of critical illness and withholding of early parenteral nutrition in the pediatric intensive care unit on long-term physical performance of children: a 4-year follow-up of the PEPaNIC randomized controlled trial. Crit Care. 2022 May 12;26(1):133. doi: 10.1186/s13054-022-04010-3.

  PMID: 35549984 DERIVED

• Verlinden I, Guiza F, Dulfer K, Van Cleemput H, Wouters PJ, Guerra GG, Joosten KF, Verbruggen SC, Vanhorebeek I, Van den Berghe G. Physical, Emotional/Behavioral, and Neurocognitive Developmental Outcomes From 2 to 4 Years After PICU Admission: A Secondary Analysis of the Early Versus Late Parenteral Nutrition Randomized Controlled Trial Cohort. Pediatr Crit Care Med. 2022 Aug 1;23(8):580-592. doi: 10.1097/PCC.0000000000002971. Epub 2022 May 9.

  PMID: 35522534 DERIVED

• Jacobs A, Guiza F, Verlinden I, Dulfer K, Garcia Guerra G, Joosten K, Verbruggen SC, Vanhorebeek I, Van den Berghe G. Differential DNA methylation by early versus late parenteral nutrition in the PICU: a biological basis for its impact on emotional and behavioral problems documented 4 years later. Clin Epigenetics. 2021 Jul 27;13(1):146. doi: 10.1186/s13148-021-01124-3.

  PMID: 34315515 DERIVED

• Verlinden I, Dulfer K, Vanhorebeek I, Guiza F, Hordijk JA, Wouters PJ, Guerra GG, Joosten KF, Verbruggen SC, Van den Berghe G. Role of age of critically ill children at time of exposure to early or late parenteral nutrition in determining the impact hereof on long-term neurocognitive development: A secondary analysis of the PEPaNIC-RCT. Clin Nutr. 2021 Mar;40(3):1005-1012. doi: 10.1016/j.clnu.2020.07.004. Epub 2020 Jul 14.

  PMID: 32758384 DERIVED

• Jacobs A, Dulfer K, Eveleens RD, Hordijk J, Van Cleemput H, Verlinden I, Wouters PJ, Mebis L, Guerra GG, Joosten K, Verbruggen SC, Guiza F, Vanhorebeek I, Van den Berghe G. Long-term developmental effect of withholding parenteral nutrition in paediatric intensive care units: a 4-year follow-up of the PEPaNIC randomised controlled trial. Lancet Child Adolesc Health. 2020 Jul;4(7):503-514. doi: 10.1016/S2352-4642(20)30104-8.

  PMID: 32562632 DERIVED

• Hordijk J, Verbruggen S, Vanhorebeek I, Guiza F, Wouters P, Van den Berghe G, Joosten K, Dulfer K. Health-related quality of life of children and their parents 2 years after critical illness: pre-planned follow-up of the PEPaNIC international, randomized, controlled trial. Crit Care. 2020 Jun 16;24(1):347. doi: 10.1186/s13054-020-03059-2.

  PMID: 32546247 DERIVED

• van Puffelen E, Hulst JM, Vanhorebeek I, Dulfer K, Van den Berghe G, Joosten KFM, Verbruggen SCAT. Effect of late versus early initiation of parenteral nutrition on weight deterioration during PICU stay: Secondary analysis of the PEPaNIC randomised controlled trial. Clin Nutr. 2020 Jan;39(1):104-109. doi: 10.1016/j.clnu.2019.02.014. Epub 2019 Mar 4.

  PMID: 30879734 DERIVED

• van Puffelen E, Hulst JM, Vanhorebeek I, Dulfer K, Van den Berghe G, Verbruggen SCAT, Joosten KFM. Outcomes of Delaying Parenteral Nutrition for 1 Week vs Initiation Within 24 Hours Among Undernourished Children in Pediatric Intensive Care: A Subanalysis of the PEPaNIC Randomized Clinical Trial. JAMA Netw Open. 2018 Sep 7;1(5):e182668. doi: 10.1001/jamanetworkopen.2018.2668.

  PMID: 30646158 DERIVED

• Verstraete S, Verbruggen SC, Hordijk JA, Vanhorebeek I, Dulfer K, Guiza F, van Puffelen E, Jacobs A, Leys S, Durt A, Van Cleemput H, Eveleens RD, Garcia Guerra G, Wouters PJ, Joosten KF, Van den Berghe G. Long-term developmental effects of withholding parenteral nutrition for 1 week in the paediatric intensive care unit: a 2-year follow-up of the PEPaNIC international, randomised, controlled trial. Lancet Respir Med. 2019 Feb;7(2):141-153. doi: 10.1016/S2213-2600(18)30334-5. Epub 2018 Sep 14.

  PMID: 30224325 DERIVED

• Verstraete S, Vanhorebeek I, van Puffelen E, Derese I, Ingels C, Verbruggen SC, Wouters PJ, Joosten KF, Hanot J, Guerra GG, Vlasselaers D, Lin J, Van den Berghe G. Leukocyte telomere length in paediatric critical illness: effect of early parenteral nutrition. Crit Care. 2018 Feb 21;22(1):38. doi: 10.1186/s13054-018-1972-6.

  PMID: 29463275 DERIVED

• van Puffelen E, Polinder S, Vanhorebeek I, Wouters PJ, Bossche N, Peers G, Verstraete S, Joosten KFM, Van den Berghe G, Verbruggen SCAT, Mesotten D. Cost-effectiveness study of early versus late parenteral nutrition in critically ill children (PEPaNIC): preplanned secondary analysis of a multicentre randomised controlled trial. Crit Care. 2018 Jan 15;22(1):4. doi: 10.1186/s13054-017-1936-2.

  PMID: 29335014 DERIVED

• Fivez T, Kerklaan D, Mesotten D, Verbruggen S, Wouters PJ, Vanhorebeek I, Debaveye Y, Vlasselaers D, Desmet L, Casaer MP, Garcia Guerra G, Hanot J, Joffe A, Tibboel D, Joosten K, Van den Berghe G. Early versus Late Parenteral Nutrition in Critically Ill Children. N Engl J Med. 2016 Mar 24;374(12):1111-22. doi: 10.1056/NEJMoa1514762. Epub 2016 Mar 15.

  PMID: 26975590 DERIVED

• Fivez T, Kerklaan D, Verbruggen S, Vanhorebeek I, Verstraete S, Tibboel D, Guerra GG, Wouters PJ, Joffe A, Joosten K, Mesotten D, Van den Berghe G. Impact of withholding early parenteral nutrition completing enteral nutrition in pediatric critically ill patients (PEPaNIC trial): study protocol for a randomized controlled trial. Trials. 2015 May 1;16:202. doi: 10.1186/s13063-015-0728-8.

  PMID: 25927936 DERIVED

MeSH Terms

Conditions

Critical Illness

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Greet Van den Berghe, MD PhD

  KU Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Dept Intensive Care Medicine

Study Record Dates

• First Submitted: February 16, 2012
• First Posted: February 22, 2012
• Study Start: June 1, 2012
• Primary Completion: March 1, 2016
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 12, 2024

Record last verified: 2024-02

Locations

BE (1); CA (1); NL (1)