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

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.

Figure 1. Participant Flow of VIDA Trial

VIDA indicates Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma. Postrandomization dropouts were included in the analysis as censored observations. ^a Details for those screened but ineligible were not collected. ^bThe most common reasons were predicted forced expiratory volume in the first second of expiration (FEV₁) greater than 90% (n = 286; a subsequent protocol modification removed this criteria), did not have a provocative concentration of methacholine at which FEV₁ decreased by 20% or did not qualify for challenge (n = 60), too few symptoms (n = 52), and predicted FEV₁ of less than 50% (n =41).

Figure 2. Primary Treatment Failure Outcome

Vertical bars represent censored events. The adjusted hazard ratio for time from randomization to first treatment failure was 0.9 (95% CI, 0.6–1.3) for the vitamin D₃ vs placebo treatment groups (P = .54).

Figure 3. Secondary Exacerbation Outcome

The first data point corresponds to the number of exacerbations that occurred during the first 4 weeks of treatment. The adjusted hazard ratio for cumulative number of exacerbations that occurred over the course of the trial was 0.63 (95% CI, 0.39–1.01; P = .05).