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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).

Authors :
O'Hearn, Katie
Menon, Kusum
Weiler, Hope A.
Amrein, Karin
Fergusson, Dean
Gunz, Anna
Bustos, Raul
Campos, Roberto
Catalan, Valentina
Roedl, Siegfried
Tsampalieros, Anne
Barrowman, Nick
Geier, Pavel
Henderson, Matthew
Khamessan, Ali
Lawson, Margaret L.
McIntyre, Lauralyn
Redpath, Stephanie
Jones, Glenville
Kaufmann, Martin
Source :
BMC Pediatrics; 7/17/2023, Vol. 23 Issue 1, p1-16, 16p
Publication Year :
2023

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 Results: Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary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. Trial Registration. Clinicaltrials.gov NCT02452762 Registered 25/05/2015. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14712431
Volume :
23
Issue :
1
Database :
Complementary Index
Journal :
BMC Pediatrics
Publication Type :
Academic Journal
Accession number :
169942870
Full Text :
https://doi.org/10.1186/s12887-023-04205-9