Clinical Trial

. 2023 Aug 14;23(1):397.

doi: 10.1186/s12887-023-04205-9.

A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study)

Katie O'Hearn¹, Kusum Menon^{1

2}, Hope A Weiler³, Karin Amrein⁴, Dean Fergusson⁵, Anna Gunz^{6

7}, Raul Bustos^{8

9}, Roberto Campos⁸, Valentina Catalan⁸, Siegfried Roedl¹⁰, Anne Tsampalieros¹¹, Nick Barrowman¹¹, Pavel Geier², Matthew Henderson^{1

12}, Ali Khamessan¹³, Margaret L Lawson^{1

2

14}, Lauralyn McIntyre¹⁵, Stephanie Redpath², Glenville Jones¹⁶, Martin Kaufmann¹⁶, Dayre McNally^{17

18}; Canadian Critical Care Trials Group

Affiliations

¹ Research Institute, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
² Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada.
³ School of Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Canada.
⁴ Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
⁵ Faculty of Medicine, University of Ottawa, Ottawa, Canada.
⁶ Department of Paediatrics, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5W9, Canada.
⁷ Child Health Research Institute, London, ON, N6A 5W9, Canada.
⁸ Clínica Sanatorio Alemán, Unidad de Cuidados Intensivos Pediátricos, Concepción, Chile.
⁹ Facultad de Medicine Y Ciencia, UCI Pediátrica Hospital Guillermo Grant Benavente Concepción, Universidad San Sebastián, Concepción, Chile.
¹⁰ Department of Paediatrics and Adolescent Medicine, Joint Facilities, Medical University of Graz, Graz, Austria.
¹¹ Clinical Research Unit, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
¹² Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Newborn Screening Ontario, Ottawa, Canada.
¹³ Euro-Pharm International Canada Inc, Montreal, Canada.
¹⁴ Division of Endocrinology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Canada.
¹⁵ Department of Medicine (Division of Critical Care), Ottawa Hospital Research Institute (OHRI), University of Ottawa, Ottawa, Canada.
¹⁶ Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada.
¹⁷ Research Institute, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada. dmcnally@cheo.on.ca.
¹⁸ Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada. dmcnally@cheo.on.ca.

PMID: 37580663
PMCID: PMC10424361
DOI: 10.1186/s12887-023-04205-9

Clinical Trial

A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study)

Katie O'Hearn et al. BMC Pediatr. 2023.

. 2023 Aug 14;23(1):397.

doi: 10.1186/s12887-023-04205-9.

Authors

Affiliations

¹ Research Institute, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
² Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada.
³ School of Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Canada.
⁴ Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
⁵ Faculty of Medicine, University of Ottawa, Ottawa, Canada.
⁶ Department of Paediatrics, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5W9, Canada.
⁷ Child Health Research Institute, London, ON, N6A 5W9, Canada.
⁸ Clínica Sanatorio Alemán, Unidad de Cuidados Intensivos Pediátricos, Concepción, Chile.
⁹ Facultad de Medicine Y Ciencia, UCI Pediátrica Hospital Guillermo Grant Benavente Concepción, Universidad San Sebastián, Concepción, Chile.
¹⁰ Department of Paediatrics and Adolescent Medicine, Joint Facilities, Medical University of Graz, Graz, Austria.
¹¹ Clinical Research Unit, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
¹² Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Newborn Screening Ontario, Ottawa, Canada.
¹³ Euro-Pharm International Canada Inc, Montreal, Canada.
¹⁴ Division of Endocrinology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Canada.
¹⁵ Department of Medicine (Division of Critical Care), Ottawa Hospital Research Institute (OHRI), University of Ottawa, Ottawa, Canada.
¹⁶ Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada.
¹⁷ Research Institute, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada. dmcnally@cheo.on.ca.
¹⁸ Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada. dmcnally@cheo.on.ca.

PMID: 37580663
PMCID: PMC10424361
DOI: 10.1186/s12887-023-04205-9

Abstract

Background: Vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU.

Methods: We conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D > 75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial.

Results: Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration > 75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean 25(OH)D concentration in the treatment arm was 125.9 nmol/L (SD 63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%).

Conclusions: A single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up.

Clinicaltrials: gov NCT02452762 Registered 25/05/2015.

Keywords: Critical care; Feasibility; Pediatrics; Randomized controlled trial; Vitamin D; Vitamin D deficiency.

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Conflict of interest statement

Dr. Khamessan is employed by Euro-Pharm International Canada Inc. Dr. Khamessan and Euro-Pharm International Canada Inc., at the request of the investigative team, developed and prepared the concentrated vitamin D solution used in the study. All other authors have no competing interests as defined by BMC, or other interests that might be perceived to influence the results and/or discussion reported in this paper.

Figures

**Fig. 1**
Legend: CONSORT diagram. Abbreviations: ICU: intensive care unit; RDA: recommended dietary allowance; CVS: cardiovascular surgery; OR – Operating room; VDD: vitamin D deficiency; NPO: No per oral

**Fig. 2**
Distribution of plasma 25(OH)D concentration prior to hospital discharge (n = 56). Distribution of plasma 25(OH)D concentration in nmol/L (based on clinical and imputed samples) prior to hospital discharge by treatment arm. In each arm, dots represent individual observations, the box represents the 25^th and 75^th percentiles and the heavy horizontal line represents the median. Points above the dashed horizontal line at 75 nmol/L represent individuals who have had normalization of vitamin D status

See this image and copyright information in PMC

References

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A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study)

Affiliations

A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study)

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical