High-dose Vitamin D Versus Placebo To Prevent Complications In ...

Outcomes and follow-up

Follow-up was limited to hospitalization. During the first seven days blood pressure, heart rate, pulse oximetry (SpO2), temperature, inspired fraction of oxygen (FiO2), respiratory rate, and clinical and adverse events were recorded. In the cases that remained hospitalized for more than seven days, clinical and adverse events were recorded from day 8 until day 30, the discharge or death, whichever occurred first.

The primary outcome was the change in the rSOFA between baseline and the highest rSOFA recorded up to day 7. The rSOFA was calculated by using the SpO2 instead the partial pressure of oxygen in arterial blood (PaO2), since was expected that most patients would not have arterial blood draws during hospitalization [23–25]. The rSOFA score was calculated with participant breathing room air, however, for participants with oxygen supplementation requirement and for whom treating physician judged inapproppriate to temporary interrupt, a guide for FiO2 estimation was provided to investigators (S2 File). Values of ratios SpO2/FiO2 for rSOFA calculations were as follows: > = 400, rSOFA 0; <400 and > = 300, rSOFA 1; <300 and > = 200, rSOFA 2; <200 and > = 100, rSOFA 3; <100, rSOFA 4.

Secondary outcomes included the change in SpO2 between baseline and the lower value recorded during the first seven days; desaturation, defined as SpO2 ≤ 90%; the combined end-point of oxygen supplementation >40%, non-invasive mechanical ventilation or invasive mechanical ventilation (this was the primary outcome of the second stage in the case the study proceed); the change in the quick SOFA between baseline and the highest value recorded during the first 7 days [26]; the requirement of invasive mechanical ventilation; the intensive care unit admission (ICU); the length of hospital stay; the ICU length of stay; acute kidney injury; and the in-hospital mortality.

Serious adverse events were defined as any occurrence in a participant that caused death, was life-threatening, prolonged the hospitalization, caused significant or persistent disability and/or was judged by investigators to represent a significant risk for participant.

A sample of 16 participants from two study sites had blood samples draws for measurement of serum 25-hydroxyvitamin D (25-OH VitD), at baseline and after 3 to 7 days after treatment. Serum 25-OH VitD levels were determined quantitatively by chemiluminescence immunoassay in a central laboratory (A98856, Access 25(OH) Vitamin D Total, Beckman Coulter Inc., USA) [27].