Impact of withholding early parenteral nutrition completing enteral nutrition in pediatric critically ill patients (PEPaNIC trial): study protocol for a randomized controlled trial.
BACKGROUND
The state-of-the-art nutrition used for critically ill children is based essentially on expert opinion and extrapolations from adult studies or on studies in non-critically ill children. In critically ill adults, withholding parenteral nutrition (PN) during the first week in ICU improved outcome, as compared with early supplementation of insufficient enteral nutrition (EN) with PN. We hypothesized that withholding PN in children early during critical illness reduces the incidence of new infections and accelerates recovery.


METHODS
The Pediatric Early versus Late Parenteral Nutrition in Intensive Care Unit (PEPaNIC) study is an investigator-initiated, international, multicenter, randomized controlled trial (RCT) in three tertiary referral pediatric intensive care units (PICUs) in three countries on two continents. This study compares early versus late initiation of PN when EN fails to reach preset caloric targets in critically ill children. In the early-PN (control, standard of care) group, PN comprising glucose, lipids and amino acids is administered within the first days to reach the caloric target. In the late-PN (intervention) group, PN completing EN is only initiated beyond PICU-day 7, when EN fails. For both study groups, an early EN protocol is applied and micronutrients are administered intravenously. The primary assessor-blinded outcome measures are the incidence of new infections during PICU-stay and the duration of intensive care dependency. The sample size (n = 1,440, 720 per arm) was determined in order to detect a 5% absolute reduction in PICU infections, with at least 80% 1-tailed power (70% 2-tailed) and an alpha error rate of 5%. Based on the actual incidence of new PICU infections in the control group, the required sample size was confirmed at the time of an a priori- planned interim-analysis focusing on the incidence of new infections in the control group only.


CONCLUSIONS
Clinical evidence in favor of early administration of PN in critically ill children is currently lacking, despite potential benefit but also known side effects. This large international RCT will help physicians to gain more insight in the clinical effects of omitting PN during the first week of critical illness in children.


BACKGROUND
ClinicalTrials.gov: NCT01536275 on 16 February 2012.
Clinical Department and Laboratory of Intensive Care Medicine, Academic Division Cellular and Molecular Medicine, KU Leuven University and Hospital, Herestraat 49, B-3000, Leuven, Belgium. tom.fivez@med.kuleuven.be.
Tom
T
Fivez
Intensive Care Unit, Department of Pediatrics and Pediatric Surgery, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands. d.kerklaand@erasmusmc.nl.
Dorian
D
Kerklaan
Intensive Care Unit, Department of Pediatrics and Pediatric Surgery, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands. s.verbruggen@erasmusmc.nl.
Sascha
S
Verbruggen
Clinical Department and Laboratory of Intensive Care Medicine, Academic Division Cellular and Molecular Medicine, KU Leuven University and Hospital, Herestraat 49, B-3000, Leuven, Belgium. ilse.vanhorebeek@med.kuleuven.be.
Ilse
I
Vanhorebeek
Clinical Department and Laboratory of Intensive Care Medicine, Academic Division Cellular and Molecular Medicine, KU Leuven University and Hospital, Herestraat 49, B-3000, Leuven, Belgium. soren.verstraete@med.kuleuven.be.
Sören
S
Verstraete
Intensive Care Unit, Department of Pediatrics and Pediatric Surgery, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands. d.tibboel@erasmusmc.nl.
Dick
D
Tibboel
Department of Pediatrics, Intensive Care Unit, University Alberta, Stollery Children's Hospital, Edmonton, AB, Canada. gonzalo.guerra@albertahealthservices.ca.
Gonzalo Garcia
GG
Guerra
Clinical Department and Laboratory of Intensive Care Medicine, Academic Division Cellular and Molecular Medicine, KU Leuven University and Hospital, Herestraat 49, B-3000, Leuven, Belgium. pieter.wouters@med.kuleuven.be.
Pieter J
PJ
Wouters
Department of Pediatrics, Intensive Care Unit, University Alberta, Stollery Children's Hospital, Edmonton, AB, Canada. ari.joffe@albertahealthservices.ca.
Ari
A
Joffe
Intensive Care Unit, Department of Pediatrics and Pediatric Surgery, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands. k.joosten@erasmusmc.nl.
Koen
K
Joosten
Clinical Department and Laboratory of Intensive Care Medicine, Academic Division Cellular and Molecular Medicine, KU Leuven University and Hospital, Herestraat 49, B-3000, Leuven, Belgium. dieter.mesotten@med.kuleuven.be.
Dieter
D
Mesotten
Clinical Department and Laboratory of Intensive Care Medicine, Academic Division Cellular and Molecular Medicine, KU Leuven University and Hospital, Herestraat 49, B-3000, Leuven, Belgium. greet.vandenberghe@med.kuleuven.be.
Greet
G
Van den Berghe
D000293:Adolescent; D000416:Alberta / Q000453:epidemiology; D001530:Belgium / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D003141:Communicable Diseases / Q000175:diagnosis / Q000453:epidemiology; D016638:Critical Illness; D002149:Energy Intake; D004750:Enteral Nutrition / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D015278:Intensive Care Units, Pediatric; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D010288:Parenteral Nutrition / Q000009:adverse effects / Q000379:methods*; D020127:Recovery of Function; D012107:Research Design; D018401:Sample Size; D062606:Tertiary Care Centers; D013997:Time Factors; D016896:Treatment Outcome