ORIGINAL ARTICLE FREE PREVIEW
Early High-Dose Vitamin D3 for Critically Ill, Vitamin D–Deficient Patients
The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network
N Engl J Med December 11, 2019
DOI: 10.1056/NEJMoa1911124
Abstract
BACKGROUND 背景
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.
维生素D缺乏是造成危重病患者罹患率及病死率常见的可逆转的原因。在急性危重病期间补充维生素D的潜在获益需要进一步研究。
METHODS 方法
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.
我们进行了一项随机、双盲、安慰剂对照、3期临床试验，对维生素D缺乏的死亡高危患者早期补充维生素D。患者入住ICU后12小时内进行随机分组。符合入选标准的患者经肠道使用单剂540,000 IU维生素D或安慰剂。主要预后终点为90天全因病死率。
RESULTS 结果
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.
经过床旁筛查，共有1360名患者维生素D缺乏并接受随机分组。其中，后续试验检查发现1078名患者存在基线维生素D缺乏 (25-羟维生素D 水平 <20 ng/ml [50 nmol/L])，这些患者纳入主要分析人群。第3天时，维生素D组患者25-羟维生素D平均水平为 46.9±23.2 ng/ml (117±58 nmol/L)，安慰剂组患者为 11.4±5.6 ng/ml (28±14 nmol/L) (差异 35.5 ng/ml; 95% 可信区间 [CI], 31.5 to 39.6)。维生素D组90天病死率为 23.5% (125/531)，安慰剂组为 20.6% (109/528) (差异, 2.9 个百分点; 95% CI, −2.1 to 7.9; P=0.26)。两组间次要临床、生理或安全性终点均无临床重要差异。基线水平维生素D缺乏的严重程度不影响治疗分组与病死率的相关性。
CONCLUSIONS 结论
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.
对于维生素D缺乏的危重病患者，早期经肠道给予大剂量维生素D不能改善90天病死率或其他非致死预后指标。
(Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314
