Importance Severe asthma exacerbations cause significant morbidity and costs. Whether vitamin D3 supplementation reduces severe childhood asthma exacerbations is unclear. Objective To determine whether vitamin D3 supplementation improves the time to a severe exacerbation in children with asthma and low vitamin D levels. Design, Setting, and Participants The Vitamin D to Prevent Severe Asthma Exacerbations (VDKA) Study was a randomized, double-blind, placebo-controlled clinical trial of vitamin D3 supplementation to improve the time to severe exacerbations in high-risk children with asthma aged 6 to 16 years taking low-dose inhaled corticosteroids and with serum 25-hydroxyvitamin D levels less than 30 ng/mL. Participants were recruited from 7 US centers. Enrollment started in February 2016, with a goal of 400 participants; the trial was terminated early (March 2019) due to futility, and follow-up ended in September 2019. Interventions Participants were randomized to vitamin D3, 4000 IU/d (n = 96), or placebo (n = 96) for 48 weeks and maintained with fluticasone propionate, 176 μg/d (6-11 years old), or 220 μg/d (12-16 years old). Main Outcomes and Measures The primary outcome was the time to a severe asthma exacerbation. Secondary outcomes included the time to a viral-induced severe exacerbation, the proportion of participants in whom the dose of inhaled corticosteroid was reduced halfway through the trial, and the cumulative fluticasone dose during the trial. Results Among 192 randomized participants (mean age, 9.8 years; 77 girls [40%]), 180 (93.8%) completed the trial. A total of 36 participants (37.5%) in the vitamin D3 group and 33 (34.4%) in the placebo group had 1 or more severe exacerbations. Compared with placebo, vitamin D3 supplementation did not significantly improve the time to a severe exacerbation: the mean time to exacerbation was 240 days in the vitamin D3 group vs 253 days in the placebo group (mean group difference, -13.1 days [95% CI, -42.6 to 16.4]; adjusted hazard ratio, 1.13 [95% CI, 0.69 to 1.85]; P = .63). Vitamin D3 supplementation, compared with placebo, likewise did not significantly improve the time to a viral-induced severe exacerbation, the proportion of participants whose dose of inhaled corticosteroid was reduced, or the cumulative fluticasone dose during the trial. Serious adverse events were similar in both groups (vitamin D3 group, n = 11; placebo group, n = 9). Conclusions and Relevance Among children with persistent asthma and low vitamin D levels, vitamin D3 supplementation, compared with placebo, did not significantly improve the time to a severe asthma exacerbation. The findings do not support the use of vitamin D3 supplementation to prevent severe asthma exacerbations in this group of patients. Trial Registration ClinicalTrials.gov Identifier: NCT02687815.

中文翻译：

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维生素 D3 补充剂对低维生素 D 水平哮喘儿童严重哮喘发作的影响

重要性 严重的哮喘发作会导致显着的发病率和费用。补充维生素 D3 是否能减少严重的儿童哮喘发作尚不清楚。目的 确定补充维生素 D3 是否能缩短维生素 D 水平低的哮喘儿童严重恶化的时间。设计、设置和参与者 维生素 D 预防严重哮喘急性发作 (VDKA) 研究是一项随机、双盲、安慰剂对照临床试验，补充维生素 D3 以缩短高危儿童哮喘严重恶化的时间。 6 至 16 岁服用低剂量吸入性皮质类固醇且血清 25-羟基维生素 D 水平低于 30 ng/mL。参与者是从 7 个美国中心招募的。2016 年 2 月开始报名，目标是 400 人；该试验因无效而提前（2019 年 3 月）终止，随访于 2019 年 9 月结束。 干预措施 参与者随机接受维生素 D3，4000 IU/d（n = 96）或安慰剂（n = 96），为期 48 周并用丙酸氟替卡松维持，176 μg/d（6-11 岁）或 220 μg/d（12-16 岁）。主要结果和措施 主要结果是严重哮喘恶化的时间。次要结果包括病毒引起的严重恶化的时间、在试验中途减少吸入皮质类固醇剂量的参与者比例，以及试验期间氟替卡松的累积剂量。结果 在 192 名随机参与者（平均年龄 9.8 岁；77 名女孩 [40%]）中，180 名 (93.8%) 完成了试验。维生素 D3 组共有 36 名参与者 (37.5%) 和 33 名 (34. 4%) 在安慰剂组中出现 1 次或多次严重恶化。与安慰剂相比，补充维生素 D3 并没有显着改善严重恶化的时间：维生素 D3 组的平均恶化时间为 240 天，而安慰剂组为 253 天（平均组间差异，-13.1 天 [95% CI ，-42.6 至 16.4]；调整后的风险比为 1.13 [95% CI，0.69 至 1.85]；P = .63）。与安慰剂相比，维生素 D3 补充剂同样没有显着改善病毒引起的严重恶化的时间，减少吸入皮质类固醇剂量的参与者比例，或试验期间氟替卡松的累积剂量。两组的严重不良事件相似（维生素 D3 组，n = 11；安慰剂组，n = 9）。结论和相关性 在患有持续性哮喘和低维生素 D 水平的儿童中，与安慰剂相比，补充维生素 D3 并没有显着改善哮喘严重恶化的时间。研究结果不支持在这组患者中使用维生素 D3 补充剂来预防严重的哮喘发作。试验注册 ClinicalTrials.gov 标识符：NCT02687815。