Effect of Vitamin D3 Supplementation on Severe Asthma Exacerbations in Children With Asthma and Low Vitamin D Levels: The VDKA Randomized Clinical Trial
Effect of Vitamin D3 Supplementation on Severe Asthma Exacerbations in Children With Asthma and Low Vitamin D Levels: The VDKA Randomized Clinical Trial
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DOI：
10.1001/jama.2020.12384
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发表时间：
2020-08-25
影响因子：
120.7
通讯作者：
Celedon, Juan C.
中科院分区：
文献类型：
--
作者：
Forno, Erick;Bacharier, Leonard B.;Celedon, Juan C.
Key PointsQuestionIn high-risk children with persistent asthma and low vitamin D levels, does vitamin D-3 supplementation prolong the time to a severe asthma exacerbation? FindingsIn this randomized clinical trial that included 192 children, vitamin D-3 supplementation, compared with placebo, did not significantly improve the time to a severe asthma exacerbation (adjusted hazard ratio, 1.13). MeaningThe findings from this trial do not support the use of vitamin D-3 supplementation to improve the time to a severe asthma exacerbation in children with asthma and low serum vitamin D levels.ImportanceSevere asthma exacerbations cause significant morbidity and costs. Whether vitamin D-3 supplementation reduces severe childhood asthma exacerbations is unclear. ObjectiveTo determine whether vitamin D-3 supplementation improves the time to a severe exacerbation in children with asthma and low vitamin D levels. Design, Setting, and ParticipantsThe Vitamin D to Prevent Severe Asthma Exacerbations (VDKA) Study was a randomized, double-blind, placebo-controlled clinical trial of vitamin D-3 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. InterventionsParticipants were randomized to vitamin D-3, 4000 IU/d (n=96), or placebo (n=96) for 48 weeks and maintained with fluticasone propionate, 176 mu g/d (6-11 years old), or 220 mu g/d (12-16 years old). Main Outcomes and MeasuresThe 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. ResultsAmong 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 D-3 group and 33 (34.4%) in the placebo group had 1 or more severe exacerbations. Compared with placebo, vitamin D-3 supplementation did not significantly improve the time to a severe exacerbation: the mean time to exacerbation was 240 days in the vitamin D-3 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 D-3 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 D-3 group, n=11; placebo group, n=9). Conclusions and RelevanceAmong children with persistent asthma and low vitamin D levels, vitamin D-3 supplementation, compared with placebo, did not significantly improve the time to a severe asthma exacerbation. The findings do not support the use of vitamin D-3 supplementation to prevent severe asthma exacerbations in this group of patients. Trial RegistrationClinicalTrials.gov Identifier: NCT02687815This randomized trial compares the effects of vitamin D(3 )vs placebo on time to severe exacerbation in children with asthma and low vitamin D levels.
