The VITdALIZE-KIDS trial, a phase III, multicenter, randomized, double-blind study, is underway to determine if rapid normalization of vitamin D deficiency improves health-related quality of life (HRQL) in critically ill children admitted to pediatric intensive care units (PICUs). This pragmatic trial, conducted in collaboration with the Canadian Critical Care Trials Group (CCCTG), seeks to address the impact of high-dose vitamin D supplementation on various clinical outcomes in this vulnerable population.
Trial Design and Setting
The VITdALIZE-KIDS trial aims to recruit 766 patients from 11 academic PICUs across Canada. Participants are randomized 1:1 to either the intervention arm, receiving a single enteral dose of cholecalciferol (vitamin D3) at 10,000 IU/kg (maximum 400,000 IU), or the control arm, receiving a placebo solution. Randomization is stratified by site to account for variations in local practices. The trial adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist.
Patient Enrollment and Procedures
Eligible participants are identified and screened daily in the PICUs. Informed consent is obtained via site-approved approaches. Patients with a 25OHD level less than 50 nmol/L are considered eligible and randomized. Blood and urine samples are collected at enrollment and post-intervention for a subset of participants for metabolomic analysis. All trial personnel, including healthcare providers and participants/families, are blinded to the treatment assignment.
Intervention and Outcomes
The primary outcome of the VITdALIZE-KIDS trial is HRQL at 28 ± 7 days after intervention, measured using the Pediatric Quality of Life Inventory Scale (PedsQL™) 4.0 Generic Acute Scales for children aged 2-17 and the PedsQL™ Infant Scales for infants aged 1-24 months. Secondary outcomes include functional status, length of mechanical ventilation, PICU and hospital length of stay, and adverse events. A metabolomics sub-study will explore the effects of rapid vitamin D deficiency correction on human metabolism, including stress response, immunomodulation, and mitochondrial function.
Safety and Monitoring
Participants are monitored for adverse events (AEs) throughout their hospital stay and during follow-up periods. The trial employs a specific definition of AEs tailored to the critical care setting, focusing on events potentially related to vitamin D administration or research procedures. A Data Safety Monitoring Board (DSMB) independently reviews trial data and provides recommendations regarding trial continuation, modification, or termination.
Statistical Analysis
The primary analytical plan will use the rank-based Mann–Whitney U test to compare 28-day PedsQL™ scores between the two arms. A two-tailed p-value < 0.05 will be considered statistically significant. Secondary and tertiary outcomes will be evaluated using appropriate statistical tests based on data type. Metabolomics data will be analyzed using multivariate and univariate statistical methods to identify metabolites associated with changes in serum 25OHD concentrations and HRQL.
Significance
The VITdALIZE-KIDS trial addresses a critical gap in understanding the role of vitamin D supplementation in improving outcomes for critically ill children. By focusing on HRQL as a primary outcome and incorporating a comprehensive metabolomics sub-study, this trial has the potential to provide valuable insights into the mechanisms and benefits of vitamin D optimization in the PICU setting.
