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

BMC Pediatr. 2023 Aug 14;23(1):397. 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Results: Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary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.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • Cholecalciferol* / therapeutic use
  • Critical Illness / therapy
  • Dietary Supplements
  • Double-Blind Method
  • Feasibility Studies
  • Humans
  • Intensive Care Units, Pediatric
  • Quality of Life
  • Vitamin D
  • Vitamin D Deficiency* / complications
  • Vitamin D Deficiency* / drug therapy
  • Vitamins / therapeutic use

Substances

  • Cholecalciferol
  • Vitamin D
  • Vitamins

Associated data

  • ClinicalTrials.gov/NCT02452762

Grants and funding