. 2024 Sep 19;25(1):619.

doi: 10.1186/s13063-024-08461-7.

Rapid normalization of vitamin D deficiency in PICU (VITdALIZE-KIDS): study protocol for a phase III, multicenter randomized controlled trial

Katie O'Hearn¹, Kusum Menon^{1

2}, Lisa Albrecht¹, Karin Amrein³, Philip Britz-McKibbin⁴, Florence Cayouette⁵, Karen Choong⁶, Jennifer Ruth Foster^{7

8}, Dean A Fergusson^{9

10

11}, Alejandro Floh^{12

13}, Patricia Fontela^{14

15}, Pavel Geier^{1

2}, Elaine Gilfoyle^{12

16}, Gonzalo Garcia Guerra^{17

18

19}, Anna Gunz²⁰, Erick Helmeczi⁴, Ali Khamessan²¹, Ari R Joffe^{19

22}, Laurie Lee^{23

24}, Lauralyn McIntyre^{10

25}, Srinivas Murthy²⁶, Simon J Parsons¹⁷, Tim Ramsay^{9

10}, Lindsay Ryerson^{19

22}, Marisa Tucci²⁷, Dayre McNally^{28

29}; Canadian Critical Care Trials Group

Affiliations

¹ CHEO Research Institute, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
² Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
³ Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
⁴ Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada.
⁵ Department of Pediatrics, Critical Care Division, Centre Mère-Enfant Soleil du CHU de Québec, Université Laval, Quebec City, QC, Canada.
⁶ Departments of Pediatrics and Critical Care, McMaster Children's Hospital, McMaster University, Hamilton, ON, Canada.
⁷ Department of Pediatric Critical Care, IWK Health, Halifax, NS, Canada.
⁸ Department of Critical Care, Dalhousie University, Halifax, NS, Canada.
⁹ School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada.
¹⁰ Ottawa Hospital Research Institute, Ottawa, ON, Canada.
¹¹ Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹² Department of Critical Care Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
¹³ Labatt Family Heart Centre, Division of Cardiac Surgery, Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada.
¹⁴ Division of Pediatric Critical Care, Department of Pediatrics, McGill University, Montreal, QC, Canada.
¹⁵ Department of Epidemiology, Biostatistics and Occupational Health, Department of Pediatrics, McGill University, McGill University, MontrealMontreal, QC, Canada.
¹⁶ Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁷ Pediatric Critical Care, Department of Pediatrics, University of Calgary, Alberta Children's Hospital, Calgary, Canada.
¹⁸ Department of Pediatrics, University of Alberta, Edmonton, AB, T6G 1C9, Canada.
¹⁹ Stollery Children's Hospital, Edmonton, AB, Canada.
²⁰ Department of Paediatrics, Schulich School of Medicine & Dentistry, Western University, Children's Health Research Institute, LondonLondon, ONON, Canada.
²¹ Euro-Pharm International Canada Inc, Montreal, Canada.
²² Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
²³ Department of Pediatrics, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada.
²⁴ Faculty of Nursing, University of Calgary, Calgary, AB, Canada.
²⁵ Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, Canada.
²⁶ Division of Critical Care, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
²⁷ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Sainte Justine and Montreal Heart Institute, University of Montreal, Montreal, QC, Canada.
²⁸ CHEO Research Institute, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada. dmcnally@cheo.on.ca.
²⁹ Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. dmcnally@cheo.on.ca.

PMID: 39300483
PMCID: PMC11414195
DOI: 10.1186/s13063-024-08461-7

Rapid normalization of vitamin D deficiency in PICU (VITdALIZE-KIDS): study protocol for a phase III, multicenter randomized controlled trial

Katie O'Hearn et al. Trials. 2024.

. 2024 Sep 19;25(1):619.

doi: 10.1186/s13063-024-08461-7.

Authors

Affiliations

¹ CHEO Research Institute, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
² Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
³ Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
⁴ Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada.
⁵ Department of Pediatrics, Critical Care Division, Centre Mère-Enfant Soleil du CHU de Québec, Université Laval, Quebec City, QC, Canada.
⁶ Departments of Pediatrics and Critical Care, McMaster Children's Hospital, McMaster University, Hamilton, ON, Canada.
⁷ Department of Pediatric Critical Care, IWK Health, Halifax, NS, Canada.
⁸ Department of Critical Care, Dalhousie University, Halifax, NS, Canada.
⁹ School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada.
¹⁰ Ottawa Hospital Research Institute, Ottawa, ON, Canada.
¹¹ Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹² Department of Critical Care Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
¹³ Labatt Family Heart Centre, Division of Cardiac Surgery, Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada.
¹⁴ Division of Pediatric Critical Care, Department of Pediatrics, McGill University, Montreal, QC, Canada.
¹⁵ Department of Epidemiology, Biostatistics and Occupational Health, Department of Pediatrics, McGill University, McGill University, MontrealMontreal, QC, Canada.
¹⁶ Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁷ Pediatric Critical Care, Department of Pediatrics, University of Calgary, Alberta Children's Hospital, Calgary, Canada.
¹⁸ Department of Pediatrics, University of Alberta, Edmonton, AB, T6G 1C9, Canada.
¹⁹ Stollery Children's Hospital, Edmonton, AB, Canada.
²⁰ Department of Paediatrics, Schulich School of Medicine & Dentistry, Western University, Children's Health Research Institute, LondonLondon, ONON, Canada.
²¹ Euro-Pharm International Canada Inc, Montreal, Canada.
²² Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
²³ Department of Pediatrics, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada.
²⁴ Faculty of Nursing, University of Calgary, Calgary, AB, Canada.
²⁵ Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, Canada.
²⁶ Division of Critical Care, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
²⁷ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Sainte Justine and Montreal Heart Institute, University of Montreal, Montreal, QC, Canada.
²⁸ CHEO Research Institute, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada. dmcnally@cheo.on.ca.
²⁹ Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. dmcnally@cheo.on.ca.

PMID: 39300483
PMCID: PMC11414195
DOI: 10.1186/s13063-024-08461-7

Abstract

Background: The rate of vitamin D deficiency (VDD) in critically ill children worldwide has been estimated at 50%. These children are at risk of multiple organ dysfunction, chronic morbidity, and decreased health related quality of life (HRQL). Pediatric and adult ICU clinical trials suggest that VDD is associated with worse clinical outcomes, although data from supplementation trials are limited and inconclusive. Our group's phase II multicenter dose evaluation pilot study established the efficacy and safety of an enteral weight-based cholecalciferol loading dose to rapidly restore vitamin D levels in critically ill children.

Methods: Our aim is to evaluate the impact of this dosing regimen on clinical outcomes. VITdALIZE-KIDS is a pragmatic, phase III, multicenter, double-blind RCT aiming to randomize 766 critically ill children from Canadian PICUs. Participants are randomized using a 1:1 scheme to receive a single dose at enrollment of enteral cholecalciferol (10,000 IU/kg, max 400,000 IU) or placebo. Eligibility criteria include critically ill children aged newborn (> 37 weeks corrected gestational age) to < 18 years who have blood total 25-hydroxyvitamin D < 50 nmol/L. The primary objective is to determine if rapid normalization of vitamin D status improves HRQL at 28 days following enrollment. The secondary objective is to evaluate the impact of rapid normalization of vitamin D status on multiple organ dysfunction. The study includes additional tertiary outcomes including functional status, HRQL and mortality at hospital discharge and 90 days, PICU and hospital length of stay, and adverse events related to vitamin D toxicity. Additionally, we are performing comprehensive vitamin D speciation and non-targeted metabolite profiling as part of a sub-study for the first 100 participants from whom an enrollment and at least one post-intervention blood and urine sample were obtained.

Discussion: The VITdALIZE-KIDS trial is the first phase III, multicenter trial to evaluate whether rapid normalization of vitamin D status could represent a simple, inexpensive, and safe means of improving outcomes following pediatric critical illness. Recruitment was initiated in June 2019 and is expected to continue to March 2026.

Trial registration: Clinicaltrials.gov, NCT03742505. Study first submitted on November 12, 2018 https://clinicaltrials.gov/study/NCT03742505.

Keywords: Critical care; Health-related quality of life; Pediatrics; Randomized controlled trial; Vitamin D; Vitamin D deficiency.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 1**
VITdALIZE-KIDS timeline of enrolment, interventions, and assessments

See this image and copyright information in PMC

References

1. Pollack MM, Holubkov R, Funai T, et al. Simultaneous prediction of new morbidity, mortality, and survival without new morbidity from pediatric intensive care: a new paradigm for outcomes assessment. Crit Care Med. 2015;43(8):1699. - PMC - PubMed
1. Aspesberro F, Mangione-Smith R, Zimmerman JJ. Health-related quality of life following pediatric critical illness. Intensive Care Med. 2015;41(7):1235–46. - PubMed
1. Conlon NP, Breatnach C, O’Hare BP, et al. Health-related quality of life after prolonged pediatric intensive care unit stay. Pediatr Crit Care Med. 2009;10(1):41–4. - PubMed
1. Pinto NP, Rhinesmith EW, Kim TY, et al. Long-term function after pediatric critical illness: results from the survivor outcomes study. Pediatr Crit Care Med. 2017;18(3):e122–30. - PubMed
1. Lee P, Nair P, Eisman JA, et al. Vitamin D deficiency in the intensive care unit: an invisible accomplice to morbidity and mortality? Intensive Care Med. 2009;35(12):2028–32. - PubMed

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Rapid normalization of vitamin D deficiency in PICU (VITdALIZE-KIDS): study protocol for a phase III, multicenter randomized controlled trial

Affiliations

Rapid normalization of vitamin D deficiency in PICU (VITdALIZE-KIDS): study protocol for a phase III, multicenter randomized controlled trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical