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Original Investigation
August 25, 2020

Effect of Vitamin D3 Supplementation on Severe Asthma Exacerbations in Children With Asthma and Low Vitamin D Levels: The VDKA Randomized Clinical Trial

Author Affiliations
  • 1Division of Pulmonary Medicine, Department of Pediatrics, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania
  • 2Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, St Louis Children’s Hospital, Washington University at St Louis, St Louis, Missouri
  • 3Division of Allergy and Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 4Division of Pulmonary Medicine, Department of Pediatrics, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, Ohio
  • 5Division of General Pediatrics, Department of Pediatrics, University of California, San Francisco Benioff Children’s Hospital, University of California, San Francisco
  • 6Division of Pediatric Pulmonology, University Hospitals Rainbow Babies and Children’s Hospital, Case Western Reserve University, Cleveland, Ohio
  • 7Division of Allergy and Immunology, Department of Pediatrics, National Jewish Health, University of Colorado, Denver
  • 8Department of Pediatrics, University of Wisconsin-Madison School of Medicine and Public Health, Madison
  • 9Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
JAMA. 2020;324(8):752-760. doi:10.1001/jama.2020.12384
Key Points

Question  In high-risk children with persistent asthma and low vitamin D levels, does vitamin D3 supplementation prolong the time to a severe asthma exacerbation?

Findings  In this randomized clinical trial that included 192 children, vitamin D3 supplementation, compared with placebo, did not significantly improve the time to a severe asthma exacerbation (adjusted hazard ratio, 1.13).

Meaning  The findings from this trial do not support the use of vitamin D3 supplementation to improve the time to a severe asthma exacerbation in children with asthma and low serum vitamin D levels.

Abstract

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

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