VIOLET (high-dose vitamin D)
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
57.0% male
N = 1078
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
23.5%
20.6%
23.5 %
17.6 %
11.8 %
5.9 %
0.0 %
Vitamin
D
Placebo
No significant
difference ↔
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.
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