Table 3 Secondary and tertiary outcomes for the VITdAL-PICU pilot study
Outcome | Explanation of outcome analysis criteria |
|---|---|
Vitamin D-related adverse events | We will evaluate for potential toxicity using two well-accepted surrogate outcome measures: • Hypercalcemia—defined as an ionized calcium level above 1.40 mmol/L (children under 8 weeks as > 1.45 mmol/L). • Hypercalciuria—defined using age-specific norms and thresholds for calcium-creatinine ratios (see Table 4) We will also evaluate for, and report on, the occurrence of serious adverse events that could potentially be related to vitamin D. |
Vitamin D axis function | Evaluated through an analysis of blood calcium, parathyroid hormone, and 1,25(OH)2D. |
Immune function | Evaluated through an analysis of inflammatory markers (C-reactive protein, procalcitonin) and antimicrobial peptide levels (cathelicidin).a |
Feasibility outcomes | Protocol non-adherence: protocol adherence will be considered successful if (a) major protocol deviations occur with regard to study drug administration or safety procedures in < 20% of enrolled patients. Study drop out: a study dropout rate of < 10% will be considered acceptable. Evaluation of the proposed eligibility criteria: defined as our ability to predict ICU stay longer than 48 h and bloodwork access at 7 days. Patient accrual rate: defined as the number of patients enrolled over a 2-year period. We will consider the patient accrual rate acceptable if we are able to successfully enroll 67 patients within 2 years. Ability to maintain blinding: ability to maintain blinding will be considered successful if the frequency of unblinding requests from the clinical care team and from the pharmacy is < 10%. |
Phase III trial outcomes | We will assess potential outcomes for a phase III trial to better inform sample size for subsequent phases of this research program. The phase III trial outcomes that will be assessed are (i) multiorgan dysfunction (PELOD-2 score; days 0, 3, 7, and every 30 days until discharge or 90 days), (ii) readiness for PICU discharge, and (iii) quality of life measure (PedsQL™) |