Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation-A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU): Study Protocol and Analysis Plan

Luregn J Schlapbach; Kristen Gibbons; Roberta Ridolfi; Amanda Harley; Michele Cree; Debbie Long; David Buckley; Simon Erickson; Marino Festa; Shane George; Megan King; Puneet Singh; Sainath Raman; Rinaldo Bellomo; RESPOND PICU study investigators and the Australian New Zealand Intensive Care Society Paediatric Study Group (ANZICS PSG)

doi:10.3389/fped.2021.663435

Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation-A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU): Study Protocol and Analysis Plan

Front Pediatr. 2021 Apr 30:9:663435. doi: 10.3389/fped.2021.663435. eCollection 2021.

Authors

Luregn J Schlapbach^{1

2}, Kristen Gibbons¹, Roberta Ridolfi¹, Amanda Harley^{1

3

4}, Michele Cree^{1

5}, Debbie Long^{1

6}, David Buckley⁷, Simon Erickson⁸, Marino Festa^{9

10}, Shane George^{1

3

11}, Megan King³, Puneet Singh¹², Sainath Raman¹, Rinaldo Bellomo¹³; RESPOND PICU study investigators and the Australian New Zealand Intensive Care Society Paediatric Study Group (ANZICS PSG)

Affiliations

¹ Child Health Research Centre, The University of Queensland, and Paediatric Intensive Care Unit, Queensland Children's Hospital, Brisbane, QLD, Australia.
² Pediatric and Neonatal Intensive Care Unit, and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
³ Departments of Emergency Medicine and Children's Critical Care, Gold Coast University Hospital, Southport, QLD, Australia.
⁴ School of Nursing, Midwifery and Social Work, University of Queensland, Brisbane, QLD, Australia.
⁵ Pharmacy Department, Queensland Children's Hospital, Brisbane, QLD, Australia.
⁶ School of Nursing, Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, QLD, Australia.
⁷ Paediatric Intensive Care Unit, Starship Children's Hospital, Auckland, New Zealand.
⁸ Paediatric Critical Care Unit, Perth Children's Hospital, Perth, WA, Australia.
⁹ Paediatric Intensive Care Unit, Children's Hospital Westmead, Sydney, NSW, Australia.
¹⁰ Kids Critical Care Research Group, Kids Research, Sydney Children's Hospitals Network, Sydney, NSW, Australia.
¹¹ School of Medicine and Menzies Health Institute Queensland, Griffith University, Southport, QLD, Australia.
¹² Paediatric Intensive Care Unit, Sydney Children's Hospital, Sydney, NSW, Australia.
¹³ Intensive Care Research, Austin Hospital and Monash University, Melbourne, VIC, Australia.

Abstract

Introduction: Septic shock remains amongst the leading causes of childhood mortality. Therapeutic options to support children with septic shock refractory to initial resuscitation with fluids and inotropes are limited. Recently, the combination of intravenous hydrocortisone with high dose ascorbic acid and thiamine (HAT therapy), postulated to reduce sepsis-related organ dysfunction, has been proposed as a safe approach with potential for mortality benefit, but randomized trials in paediatric patients are lacking. We hypothesize that protocolised early use of HAT therapy ("metabolic resuscitation") in children with septic shock is feasible and will lead to earlier resolution of organ dysfunction. Here, we describe the protocol of the Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation-A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU). Methods and Analysis: The RESPOND PICU study is an open label randomized-controlled, two-sided multicentre pilot study conducted in paediatric intensive care units (PICUs) in Australia and New Zealand. Sixty children aged between 28 days and 18 years treated with inotropes for presumed septic shock will be randomized in a 1:1 ratio to either metabolic resuscitation (1 mg/kg hydrocortisone q6h, 30 mg/kg ascorbic acid q6h, 4 mg/kg thiamine q12h) or standard septic shock management. Main outcomes include feasibility of the study protocol and survival free of organ dysfunction censored at 28 days. The study cohort will be followed up at 28-days and 6-months post enrolment to assess neurodevelopment, quality of life and functional status. Biobanking will allow ancillary studies on sepsis biomarkers. Ethics and Dissemination: The study received ethical clearance from Children's Health Queensland Human Research Ethics Committee (HREC/18/QCHQ/49168) and commenced enrolment on June 12th, 2019. The primary study findings will be submitted for publication in a peer-reviewed journal. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12619000829112). Protocol Version: V1.8 22/7/20.

Keywords: ascorbic acid; child; hydrocortisone; intensive care; sepsis; septic shock; thiamine; vitamin C.

Copyright © 2021 Schlapbach, Gibbons, Ridolfi, Harley, Cree, Long, Buckley, Erickson, Festa, George, King, Singh, Raman, Bellomo and the RESPOND PICU study investigators and the Australian New Zealand Intensive Care Society Paediatric Study Group (ANZICS PSG).