Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial

JAMA. 2014 May;311(20):2083-91. doi: 10.1001/jama.2014.5052.

Abstract

Importance: In asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency.

Objective: To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels.

Design, setting, and participants: The VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized.

Interventions: Oral vitamin D3 (100,000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 µg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 µg/d for 8 weeks, then to 80 µg/d for 8 weeks if asthma control was maintained.

Main outcomes and measures: The primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care).

Results: Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28% [95% CI, 21%-34%] with vitamin D3 vs 29% [95% CI, 23%-35%] with placebo; adjusted hazard ratio, 0.9 [95% CI, 0.6-1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 µg/d [95% CI, 102.2-120.4 µg/d] in the vitamin D3 group vs 126.2 µg/d [95% CI, 117.2-135.3 µg/d] in the placebo group; difference of 14.9 µg/d [95% CI, 2.1-27.7 µg/d]).

Conclusions and relevance: Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma.

Trial registration: clinicaltrials.gov Identifier: NCT01248065.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Adrenal Cortex Hormones / administration & dosage*
  • Adult
  • Anti-Asthmatic Agents / administration & dosage
  • Asthma / complications
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Cholecalciferol / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Glucocorticoids / administration & dosage*
  • Humans
  • Lung / drug effects
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Pregnenediones / administration & dosage*
  • Treatment Failure
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / drug therapy*
  • Vitamins / therapeutic use*

Substances

  • Adrenal Cortex Hormones
  • Anti-Asthmatic Agents
  • Glucocorticoids
  • Pregnenediones
  • Vitamins
  • Cholecalciferol
  • ciclesonide

Associated data

  • ClinicalTrials.gov/NCT01248065

Grant support