Effect of Vitamin D as add-on Therapy for Vitamin D Insufficient Patients With Severe Asthma

Study Overview
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Brief Summary
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The purpose of the EVITA trial is to compare the effects of vitamin D therapy with placebo on reducing the dose of inhaled or oral corticosteroids in patients with severe asthma and vitamin D insufficiency.

Detailed Description
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Patients with severe asthma represent the greatest unmet medical need among the asthmatic population, in particular due to their high risk of severe exacerbations. A substantial proportion of these patients does not achieve asthma control despite even high-dose ICS and LABA treatment, necessitating add-on therapy. For these patients oral corticosteroids (OCS) are a preferred treatment modality, which will inevitably lead to severe side effects. A high Proportion of patients with severe Asthma are Vitamin D insufficient (< 30 ng/ml). It is therefore tempting to speculate that vitamin D substitution in vitamin D insufficient patients who continue to experience suboptimal asthma control on ICS and LABA or ICS/LABA plus OCS treatment may boost corticosteroid responsiveness, thereby potentially reducing corticosteroid dose requirements and improving key parameters of asthma control. The present study is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of treatment with vitamin D at a dose of 4000 IU/day administered daily following a single loading dose of 100 000 IU upon study entry over a period of 24 weeks in patients with severe asthma and vitamin D insufficiency. During the study, all patients will remain on their existing maintenance asthma therapy throughout the study, in addition to the study treatment, while reducing inhaled or oral steroids according to study protocol. The study consists of a 2-week run-in period, a 24 week double-blind treatment period including a 12 week steroid stable phase and two steroid reduction phases, followed by a follow-up visit 4 weeks after last study medication intake. The active treatment arm in this study will be standard of care plus vitamin D (loading dose of 100 000 IU upon study entry, to be followed by 4000 IU/day for the rest of the study period) while the comparator arm will be standard of care plus placebo.

Official Title
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EVITA Trial: Effect of VItamin D as add-on Therapy for Vitamin D Insufficient Patients With Severe Asthma: a Randomized, Double-blind, Placebo-controlled Trial

Conditions
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Asthma

Intervention / Treatment
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* Drug: Vitamin D3
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients, age ≥ 18 years A pulmonary specialist documented diagnosis of severe asthma according to the Global Initiative for Asthma and the German Asthma Network (GAN, www.german-asthma-net.de) Treatment with long-acting β2-agonists (LABA) and inhaled corticosteroids (ICS) at a dose of at least 1000 µg beclomethasone (or equivalent) per day, - chronic oral corticosteroid (OCS) use is allowed Stable asthma medication for ≥1 month prior to screening (≥4 months for omalizumab) Asthma Control Questionnaire (ACQ-5) score ≥ 1.5 Vitamin D insufficiency as defined by a serum vitamin D concentration of < 30 ng/ml but ≥ 10 ng/ml at screening Exclusion Criteria: Patients on vitamin D substitution Current smokers or ex-smokers with a smoking history of more than 10 pack-years Pregnant or nursing women or women who intend to become pregnant during the study Known impaired renal function (GFR < 30 ml/min) and history of physician-diagnosed nephrolithiasis Use of other investigational drugs during the study or within 30 days of screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3<br>Initial single dose 100000 IU, beginning from the second day 4000 IU/day for 24 weeks | Drug: Vitamin D3<br>* Initial single dose 100000 IU, beginning from the second day 4000 IU/day for 24 weeks.<br>* Other names: Cholecalciferol;|
| Placebo Comparator: Placebo<br>Amount of Placebo capsules corresponding to initial single dose of Vitamin D3, beginning from the second day amount of capsules corresponding to daily dose of Vitamin D for 24 weeks | Drug: Placebo<br>* Filling material: lactose monohydrate, cellulose, magnesium stearate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relative dose reduction of ICS or OCS at week 24 as assessed by total ICS or OCS dose |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exacerbations (rate of and time to first and subsequent exacerbations) as assessed by numbers of exacerbations |  | 24 weeks and 30 weeks | 
| Asthma Control as assessed by ACQ score |  | at weeks 4, 8, 12, 14, 18, 20, 24, and 28 | 
| Asthma Quality of Life as assessed by the Mini-AQLQ score |  | at weeks 12, 18, 24 and 28 | 
| Pulmonary function test results as assessed by FEV1, FVC, IC, RV, TLC, and airway resistance |  | at weeks 4, 8, 12, 14, 18, 20, 24, and 28 | 
| Levels of vitamin D as assessed by serum concentrations |  | at weeks 12, 18, 24 and 28 | 
| Proportion of patients that achieved vitamin D sufficiency |  | at week 24 | 
| Assessment of safety and tolerability as assessed by number of adverse events |  | up to 30 weeks | 
| Dyspnea as assessed by Baseline and Transition Dyspnea Indexes |  | at weeks 12, 18, 24 and 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severe asthma, vitamin D, treatment