Significant modifications to the study drug protocol
The trial intervention initially involved two doses of study drug (placebo or cholecalciferol): (i) at time of enrollment, and (ii) a day 3 dose dependent on the 25(OH)D concentration achieved. However, after randomization of the first 12 patients, the intervention was adjusted in July 2016 to a single-dose protocol administered at the time of study enrollment. There were multiple reasons for this modification. First, new literature in the adult ICU population demonstrated that administration of a single loading dose of 500,000 IU, comparable to our intervention, raised 25(OH)D concentrations by 80 (± 35) nmol/L [