6/30/23, 12:37 AM VIOLET (vitamin D) Pathway Feedback Search Clinical Topics Home Studies VIOLET (vitamin D VIOLET (vitamin D Disease Vitamin D deficiency Trial question What is the effect of early high-dose vitamin D3 supplementation in critically ill, vitamin D- deficient patients? Study design Multi-center Double blinded RCT Population Characteristics of study participants 43.0% female N = 1078 57.0% male 1078 patients (467 female, 611 male) Inclusion criteria: critically ill, vitamin D-deficient patients who were at high risk for death Key exclusion criteria: an inability to take an enteral drug, a history of kidney stones, the presence of hypercalcemia at baseline, and informed consent not being obtained in a timely manner Interventions N=538 vitamin D (a single enteral dose of 540,000 IU of vitamin D3 in liquid form, administered within 2 hours after randomization) N=540 placebo (matched placebo in liquid form, administered within 2 hours after randomization) Primary outcome All-cause mortality at 90 days https://web.pathway.md/studies/rec4NWnyYq1dZjUTZ 1/2 6/30/23, 12:37 AM VIOLET (vitamin D) Pathway 23.5 % 23.5 20.6 17.6 % 11.8 % 5.9 % No significant difference 0.0 % Vitamin D Placebo No significant difference in all-cause mortality at 90 days (23.5% vs. 20.6%; AD 2.9%, 95% CI -2.1 to 7.9) Secondary outcomes No significant difference in in-hospital mortality at 90 days (17.1% vs. 13.4%; AD 3.7%, 95% CI -0.5 to 8) Borderline significant decrease in hospital length of stay at 90 days (9.1 days vs. 10.4 days; AD -1.4 days, 95% CI -2.7 to 0) No significant difference in ventilator-free days at 28 days (21.3 days vs. 22.1 days; AD -0.8 days, 95% CI -2.1 to 0.5) Safety outcomes No significant differences in serious and nonserious adverse events, hypercalcemia, kidney stones, fall-related fractures. Significant difference in total calcium level at 14 days (8.9 mg/dl vs. 8.8 mg/dl). Conclusion In critically ill, vitamin D-deficient patients who were at high risk for death, vitamin D was not superior to placebo with respect to a all-cause mortality at 90 days. Reference National Heart, Lung, and Blood Institute PETAL Clinical Trials Network et al. Early High-Dose Vitamin D 3 for Critically Ill, Vitamin D-Deficient Patients. N Engl J Med. 2019 Dec 26;381(26):2529-2540. Open reference URL https://web.pathway.md/studies/rec4NWnyYq1dZjUTZ 2/2