BACKGROUND Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study. METHODS We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality. RESULTS A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P = 0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality. CONCLUSIONS Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. (Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314.).

中文翻译：

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早期重症维生素D缺乏症患者的大剂量维生素D3。

背景技术维生素D缺乏症是重症患者中发病率和死亡率的常见，潜在可逆因素。在急性危重病中补充维生素D的潜在益处需要进一步研究。方法我们对高危死亡的危重维生素D缺乏症患者进行了一项早期补充维生素D3的随机，双盲，安慰剂对照的3期临床试验。在决定允许患者加入重症监护病房后的12个小时内进行了随机分组。符合条件的患者接受了540,000 IU的维生素D3或匹配安慰剂的单次肠内给药。主要终点是90天全因所有地点的死亡率。结果总共有1360名患者在现场筛查期间被发现缺乏维生素D，并接受了随机分组。在这些病人中 1078名基线维生素D缺乏症（25-羟基维生素D水平，<20 ng /毫升[50 nmol /升]）已通过后续测试确认，并纳入了主要分析人群。维生素D组第三天的25-羟基维生素D的平均水平为46.9±23.2 ng /毫升（117±58 nmol /升），而安慰剂组为11.4±5.6 ng /毫升（28±14 nmol /升）（差异，每毫升35.5 ng； 95％置信区间[CI]，31.5至39.6）。维生素D组（531名患者中的125名）和安慰剂组（528名患者中的109名）的90天死亡率为23.5％（差异为2.9个百分点； 95％CI为-2.1至7.9； P = 0.26）。在二级临床，生理或安全终点方面，各组之间在临床上没有重要的差异。基线时维生素D缺乏的严重程度不影响治疗分配与死亡率之间的关联。结论就危重病，维生素D缺乏症患者的90天死亡率或其他非致命结局而言，大剂量肠内维生素D3的早期给药并未提供优于安慰剂的优势。（由美国国家心脏，肺和血液研究所资助； VIOLET ClinicalTrials.gov编号，NCT03096314。）。