Effects of Macrolides on Asthma Control

Study Overview
=================
Brief Summary
-----------------
Asthma is a common disease in Westernised societies, affecting up to 10% of the population. Corticosteroids are the most effective treatment for asthma but the therapeutic response varies considerably between individuals. A major cause of corticosteroid insensitivity in asthma is cigarette smoking. Active cigarette smoking occurs in over 25% of adults with asthma and a further 25% are ex-smokers. In a series of proof of concept clinical studies the investigators demonstrated for the first time that the efficacy of inhaled and oral corticosteroids is markedly impaired in smokers with asthma and to a lesser extent in ex-smokers with asthma. Active cigarette smoking has other detrimental effects on asthma morbidity including more severe symptoms, increased rates of hospitalisation, and accelerated decline in lung function. Smoking cessation advice is often ineffective because many adult smokers with asthma do not believe that they are personally at risk from their smoking, take many years until stopping smoking and frequently restart smoking after quitting. Alternative or additional drugs to corticosteroids are needed for smokers with asthma who are unable to obtain the clinical benefits associated with stopping smoking. In a proof of concept clinical trial the investigators will test the hypothesis that macrolides improve asthma control and reduce sputum neutrophil counts of smokers with chronic asthma.

Official Title
-----------------
Effects of Macrolides on Asthma Control, Airway Inflammation and Bacterial Colonisation in Smokers With Asthma.

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: Azithromycin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of asthma Age 18-70 Current smoker Duration of symptoms >1yr with stability for 4 weeks Able to maintain asthma without exacerbations during run in period Able to wean off other asthma medication Exclusion Criteria: Ex-smokers or never smokers Planning to quit smoking during duration of trial Patients with unstable asthma Patients with current epilepsy, psychosis or history of significant atrial or ventricular tachyarrhythmia Corrected QT-interval greater than 450msec in women, 430msec in men Low potassium levels. If can be corrected then screening can continue with confirmation of normal levels prior to taking study medication Liver disease (ALT and/or AST levels 2 or more times ULN) Significant renal disease (Creatinine or urea levels 2 or more times ULN) Any previous severe adverse reactions to macrolides Patients who are known to have specific IgE sensitivity or skin test positivity to grass pollen and a history of worsening of asthma due to hay fever will not be recruited from mid May to the end of July Upper or lower respiratory tract infection in the 4 weeks prior to randomisation. Run in period can be prolonged in this situation to have 4 weeks with no respiratory infection prior to randomisation. Patients who require medications known to interact with azithromycin On other immunosuppressants or chronic antibiotics Weight less than 45kg Frequent asthma exacerbations (greater than 4) requiring oral corticosteroids in the year prior to randomisation Current or past diagnosis of allergic-bronchopulmonary-aspergillosis Pregnancy and breast feeding Mental impairment or language difficulties that makes informed consent not possible

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Active treatment. | Drug: Azithromycin<br>* Daily dose 250mg<br>|
| Placebo Comparator: 2<br>Placebo control group. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak expiratory flow rate. |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spirometry |  | 12 weeks | 
| Asthma control score |  | 12 weeks | 
| Average of last 7 days PEF measurements |  | 12 weeks | 
| Sputum cell counts |  | 12 weeks | 
| Fraction of expired nitric oxide |  | 12 weeks | 
| Airway responsiveness to methacholine |  | 12 weeks | 
| Exacerbation rates |  | 12 weeks | 
| Cough score |  | 12 weeks | 
| Diary symptom score |  | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Asthma, Smoker, Macrolide