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A Randomized Controlled Trial of Corticosteroids in Pediatric Septic Shock: A Pilot Feasibility Study*

Menon, Kusum MSc, MD1,2; McNally, Dayre MD, PhD1,2; O’Hearn, Katharine MSc1; Acharya, Anand PhD3; Wong, Hector R. MD4; Lawson, Margaret MSc, MD1,2; Ramsay, Tim PhD5,6; McIntyre, Lauralyn MD7; Gilfoyle, Elaine MEd, MD8; Tucci, Marisa MD9; Wensley, David MBBS10; Gottesman, Ronald MD11; Morrison, Gavin MD12; Choong, Karen MSc, MB13; for the Canadian Critical Care Trials Group

Pediatric Critical Care Medicine: June 2017 - Volume 18 - Issue 6 - p 505-512
doi: 10.1097/PCC.0000000000001121
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Objective: To determine the feasibility of conducting a randomized controlled trial of corticosteroids in pediatric septic shock.

Design: Randomized, double-blind, placebo controlled trial.

Setting: Seven tertiary level PICUs in Canada.

Patients: Children newborn to 17 years old inclusive with suspected septic shock.

Intervention: Administration of IV hydrocortisone versus placebo until hemodynamic stability is achieved or for a maximum of 7 days.

Measurements and Main Results: One hundred seventy-four patients were potentially eligible of whom 101 patients met eligibility criteria. Fifty-seven patients were randomized, and 49 patients (23 and 26 patients in the hydrocortisone and placebo groups, respectively) were included in the final analysis. The mean time from screening to randomization was 2.4 ± 2.1 hours and from screening to first dose of study drug was 3.8 ± 2.6 hours. Forty-two percent of potentially eligible patients (73/174) received corticosteroids prior to randomization: 38.5% (67/174) were already on corticosteroids for shock at the time of screening, and in 3.4% (6/174), the treating physician wished to administer corticosteroids. Six of 49 randomized patients (12.2%) received open-label steroids, three in each of the hydrocortisone and placebo groups. Time on vasopressors, days on mechanical ventilation, PICU and hospital length of stay, and the rate of adverse events were not statistically different between the two groups.

Conclusions: This study suggests that a large randomized controlled trial on early use of corticosteroids in pediatric septic shock is potentially feasible. However, the frequent use of empiric corticosteroids in otherwise eligible patients remains a significant challenge. Knowledge translation activities, targeted recruitment, and alternative study designs are possible strategies to mitigate this challenge.

1Research Institute, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada.

2Department of Pediatrics, Faculty of Medicine, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.

3Department of Economics, Faculty of Public Affairs, Carleton University, Ottawa, ON, Canada.

4Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH.

5Department of Epidemiology, Ottawa Hospital Research Institute (OHRI), University of Ottawa, Ottawa, ON, Canada.

6Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI), University of Ottawa, Ottawa, ON, Canada.

7Division of Critical Care, Department of Medicine, Ottawa Hospital Research Institute (OHRI), University of Ottawa, Ottawa, ON, Canada.

8Section of Critical Care Medicine, Department of Pediatrics, Alberta Children’s Hospital, Calgary, AB, Canada.

9Department of Pediatrics, CHU Sainte-Justine Hospital, Montreal, QC, Canada.

10Department of Pediatrics, Faculty of Medicine, British Columbia Women’s and Children’s Hospital, The University of British Columbia, Vancouver, BC, Canada.

11Department of Pediatrics, Faculty of Medicine, Montreal Children’s Hospital, McGill University, Montreal, QC, Canada.

12Department of Critical Care Medicine, IWK Health Centre, Halifax, NS, Canada.

13Department of Pediatrics, McMaster Children’s Hospital, McMaster University, Hamilton, ON, Canada.

*See also p. 589.

The coordinating site was the Children’s Hospital of Eastern Ontario, and this work was performed at the British Columbia Women’s and Children’s Hospital, Alberta Children’s Hospital, Hamilton Health Sciences Center, Children’s Hospital of Eastern Ontario, Montreal Children’s Hospital, St. Justine’s Hospital, and Izaac Walton Killam Hospital for Children.

Trial Registration: Clinical Trials (NCT 02044159), http://www.clinicaltrials.gov.

Supported, in part, by Canadian Institutes of Health Research (CIHR) operating grant, Ottawa, ON, Canada.

Dr. Menon’s institution received funding from Canadian Institutes of Health Research (CIHR). Dr. McNally disclosed: work was funded through a CIHR grant. Dr. Acharya received funding from Children’s Hospital of Eastern Ontario (CHEO). Dr. Wong received support for article research from the National Institutes of Health (NIH). His institution received funding from the NIH. Dr. Lawson’s institution received funding from CIHR. Dr. Gilfoyle’s institution received funding from CHEO Research Institute (original funder CIHR), Alberta Innovates Health Solutions, Alberta Children’s Hospital Foundation, CIHR, Heart and Stroke Foundation, Alberta Health Services, and Centre Hospitalier Universitaire Sainte-Justine. Mr. Wensley disclosed: expenses for the study were covered by the CIHR grant (i.e., pharmacy and laboratory costs). He received support for article research from CIHR. Dr. Gottesman’s institution received funding from CIHR. He received support for article research from CIHR. Dr. Morrison’s institution received funding from CHEO. He disclosed off-label product use: hydrocortisone use in children with septic shock. Mrs. Choong’s institution received funding from CIHR to support research personnel in the enrollment and data collection and from Academic Health Sciences Innovation Grant. She has disclosed that she is employed by McMaster University and Hamilton Health Sciences. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Address requests for reprints to: Kusum Menon, MSc, MD, CHEO, 401 Smyth Road, Ottawa, ON K1H 8L1, Canada. E-mail: menon@cheo.on.ca

Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies