AsthmaNet Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma (VIDA)

HLB02182020a

AsthmaNet-VIDA

AN8

False

Asthma

Bronchial Diseases

Respiratory Tract Diseases

Lung Diseases, Obstructive

Lung Diseases

Respiratory Hypersensitivity

Hypersensitivity, Immediate

Hypersensitivity

Immune System Diseases

Vitamin D

Cholecalciferol

Ciclesonide

Vitamins

Micronutrients

Physiological Effects of Drugs

Bone Density Conservation Agents

Calcium-Regulating Hormones and Agents

Glucocorticoids

Hormones

Hormones, Hormone Substitutes, and Hormone Antagonists

Anti-Allergic Agents

True

True

Coded

False

Clinical Trial

Open BioLINCC Study

Adult

Drug: Vitamin D3

Drug: Ciclesonide

2020-02-21

2022-06-24

2020-02-21

None

April 2011 – January 2014

DLD

Lung

non-HIV

non-COVID

None

None

No

No

No

No

Yes, For Some Specimens

No

Some subjects allow use of their specimens for genetic use

Asthma

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

At the time of this study, guidelines recommended the use of inhaled corticosteroids as the primary anti-inflammatory controller therapy for patients with persistent asthma. However, previous studies have shown that up to 45% of patients do not have a clinical or physiological response to these agents. In children and adults with asthma, serum 25-hydroxyvitamin D levels of less than 30 ng/mL have been linked to airway hyperresponsiveness, impaired lung function, increased exacerbation frequency, and reduced corticosteroid responsiveness. VIDA was designed to determine if vitamin D supplementation would improve responsiveness to corticosteroids in patients with persistent asthma and low levels of vitamin D at baseline.

Eligible participants were aged 18 years or older with asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL. Asthma entry criteria included physician-diagnosed disease and evidence of either bronchodilator reversibility (FEV1≥12% following 180 µg of levalbuterol) or airway hyperresponsiveness (provocative concentration of methacholine at which FEV1 decreased by 20%). A total of 408 patients were randomized, with 201 randomized to the vitamin D₃ group and 207 randomized to the placebo group.

The study was a randomized, double-masked, parallel group trial, with each eligible participant randomly assigned to either placebo or high-dose vitamin D₃ (100 000 IU once, followed by 4000 IU per day for 28 weeks) added to inhaled corticosteroid (ciclesonide at a dose of 320 µg per day) and levalbuterol. Computer-generated randomization was stratified by clinical center, body mass index (BMI ≤25 vs BMI >25), and race (blacks vs all others), with treatment assignments made in random permuted blocks of size 2. The placebo vitamin D soft gelatin capsules matched in appearance those containing vitamin D₃.

After completing a 4-week run-in period of treatment with only ciclesonide and levalbuterol (prior asthma treatments were discontinued), participants were randomized. After randomization, participants entered a 12-week stability phase, in which they continued to receive 320 µg per day of ciclesonide. If the participant’s asthma symptoms were controlled, at 12 weeks patients were tapered to 160 µg per day of ciclesonide for 8 weeks, and then at 20 weeks patients were tapered to 80 µg per day of ciclesonide for 8 weeks. Participants were terminated or withdrawn from the study if they had more than 2 treatment failures or exacerbations.

Asthma symptoms were measured using an electronic diary and the Asthma Symptom Utility Index (ASUI). Participants were instructed to complete the electronic diary every morning and evening and asked to grade the following symptoms: shortness of breath, chest tightness, wheezing, cough, and phlegm or mucus. Symptoms were graded from 0 (absent) to 3 (severe). The scores on the ASUI range from 0 to 1; a higher score indicates better symptom control. Asthma control was measured using the Asthma Control Test (ACT). The scores on the ACT range from 5 to 25; higher scores indicate better asthma control. Asthma-specific quality of life was measured using the Asthma Bother Profile questionnaire. The scores on the Asthma Bother Profile range from 0 to 75; higher scores indicate poorer quality of life. Serum 25-hydroxyvitamin D level was measured at baseline and at the end of each ciclesonide treatment phase. Airway inflammation was measured by performing a differential cell count from induced sputum samples collected at the end of the 4-week run-in and at 12 weeks.

The primary end point was time to first asthma treatment failure during the 28-week study period. Treatment failure was defined as one or more of the following: peak expiratory flow of 65% or less of baseline measurement on two of three consecutive measurements; FEV1 of 80% or less of baseline measurement on two consecutive measurements; increase in levalbuterol dose of 8 puffs per day or more for 48 hours (as compared to baseline); additional use of inhaled corticosteroids or use of oral or parenteral corticosteroids for asthma; emergency department or hospitalization for asthma with systemic corticosteroid use; participant lack of satisfaction with treatment; and physician clinical judgment for safety reasons.

Vitamin D₃ did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency.

Castro M, King TS, Kunselman SJ, et al. 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;311(20):2083–2091. doi:10.1001/jama.2014.5052

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Sputum