Effects of Macrolides on Asthma Control

Phase 3

Completed

• Conditions: Asthma
• Interventions: Drug: Azithromycin; Drug: Placebo

• Registration Number: NCT00852579
• Lead Sponsor: Euan J Cameron

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-02-26
• Study First Submitted QC: 2009-02-26
• Study First Posted: 2009-02-27
• Study Start: 2009-03
• Primary Completion: 2011-08
• Study Completion: 2011-08
• Status Verified: 2011-10
• Last Update Submitted: 2011-10-18
• Last Update Posted: 2011-10-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 77

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Azithromycin	Active treatment.
2	Placebo	Placebo control group.

Primary Outcome Measures

Name	Time	Method
Peak expiratory flow rate.	12 weeks

Secondary Outcome Measures

Name	Time	Method
Asthma control score	12 weeks
Spirometry	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

Trial Locations

Locations (2)

Crosshouse Hospital; 🇬🇧 Kilmarnock, United Kingdom

Gartnavel General Hospital; 🇬🇧 Glasgow, United Kingdom