Small Particle Steroids in Refractory Asthma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether an inhaled steroid with a small particle size can be an additional treatment option in patients with refractory eosinophilic asthma.

Detailed Description
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We have identified a group of patients with refractory asthma who have ongoing eosinophilic airway inflammation despite high dose inhaled corticosteroids. Traditional inhaled steroids have a relatively proximal airway distribution which may lead to inadequate treatment of the distal airways. We aim to demonstrate that a steroid inhaler with a smaller particle size which targets the distal airways can be a useful additional treatment option in this group of patients.

Official Title
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Small Particle Inhaled Steroids in Refractory Steroid-responsive Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Ciclesonide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 ACQ >1.5 or a requirement for oral steroids twice a year or more High dose inhaled steroid (>1000mcg BDP or equivalent) Treatment with or unsuccessful trial of: long-acting beta agonist leukotriene antagonist Sputum eosinophil count >3% despite high dose inhaled steroid or >2% with serum eosinophils >0.4x10exp9/l Clinical response to 2 weeks of oral prednisolone: (any one) reduction in ACQ by 0.5 or more increase in FEV1 by 200ml normalisation of exhaled nitric oxide or reduction of >25ppb Exclusion Criteria: Current smoker, or ex-smoker for <12 months Current treatment with an extrafine steroid inhaler Respiratory infection within the last 4 weeks Pregnancy or lactation Poor compliance with usual asthma medication Clinical diagnosis of significant bronchiectasis Use of a medication which may interact with ciclesonide: ketoconazole or itraconazole ritonavir, nelfinavir

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Active Comparator: Ciclesonide<br>Ciclesonide 320 microgrammes twice daily | Drug: Ciclesonide<br>* Inhaled ciclesonide 320mcg twice daily<br>* Other names: Alvesco;|
| Placebo Comparator: Placebo<br>Placebo 2 inhalations twice daily | Drug: Placebo<br>* Matched placebo inhaler two inhalations twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in sputum eosinophil count over the trial period | Sputum will be processed for a differential cell count, with the primary outcome the difference in sputum eosinophil count between active and placebo groups at 8 weeks | 0 weeks (start), 8 weeks (finish) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in alveolar nitric oxide level over the trial period | alveolar nitric oxide has been shown to correlate with eosinophil count on BAL samples. Measured by measuring exhaled nitric oxide at multiple flow rates. | 0 weeks (start), 4 weeks, 8 weeks (finish) | 
| Change in bronchial nitric oxide level | Measured by single flow exhaled nitric oxide at 50 ml/s | 0 weeks (start), 4 weeks, 8 weeks (finish) | 
| Change in prebronchodilator FEV1 | Prebronchodilator FEV1 and FVC will be recorded with a Vitalograph Wedge Bellows spirometer | 0 weeks (start), 4 weeks, 8 weeks (finish) | 
| Change in Juniper Asthma Control Questionnaire (ACQ) score | UK English Version 2001 | 0 weeks (start), 4 weeks, 8 weeks (finish) | 
| Change in Juniper Asthma Quality of Life Questionnaire (AQLQ) score | Self-administered United Kingdom Version 1994 | 0 weeks (start), 4 weeks, 8 weeks (finish) | 
| Use of oral steroid over the trial period | Dose and duration of any additional oral corticosteroid will be documented | 0-8 weeks | 
| Number of patients with adverse events as a measure of safety and tolerability | Adverse events will be recorded throughout the trial period | 0-8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ciclesonide, Asthma, Therapeutic Uses, Pulmonary Eosinophilia, Nitric Oxide, Lung Diseases, Respiratory Tract Diseases