Journal Article

Impact of withholding early parenteral nutrition completing enteral nutrition in pediatric critically ill patients (PEPaNIC trial): study protocol for a randomized controlled trial

Guerra, Gonzalo Garcia, Van den Berghe, Greet, Tibboel, Dick, Joosten, Koen, Fivez, Tom, Kerklaan, Dorian, Verstraete, Sören, Vanhorebeek, Ilse, Joffe, Ari, Wouters, Pieter J, Mesotten, Dieter, Verbruggen, Sascha

2015

Overview

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/Design 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. Discussion 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. Trial registration ClinicalTrials.gov: NCT01536275 on 16 February 2012.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Adolescent / Alberta - epidemiology / Belgium - epidemiology / Biomedicine / Care and treatment / Child / Child, Preschool / Children / Clinical Protocols / Clinical trials / Communicable Diseases - diagnosis / Communicable Diseases - epidemiology / Comparative analysis / Critical Illness / Diseases / Energy Intake / Enteral nutrition / Enteral Nutrition - adverse effects / Enteral Nutrition - methods / Female / Gestational age / Health aspects / Health Sciences / Heart surgery / Humans / Hypotheses / Illnesses / Incidence / Infant / Infant, Newborn / Infection / Infection in children / Informed consent / Intensive care / Intensive Care Units, Pediatric / Male / Malnutrition / Medical referrals / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Metabolism / Netherlands - epidemiology / Nutrition / Nutrition therapy / Parenteral nutrition / Parenteral Nutrition - adverse effects / Parenteral Nutrition - methods / Patients / Pediatrics / Physicians / Recovery of Function / Research Design / Sample Size / Statistics for Life Sciences / Study Protocol / Tertiary Care Centers / Time Factors / Treatment Outcome