Effects of Macrolides on Asthma Control

Euan J Cameron

Status and phase

Completed

Phase 3

Conditions

Asthma

Treatments

Drug: Placebo

Drug: Azithromycin

Study type

Interventional

Funder types

Other

Identifiers

NCT00852579

MRC Grant G0701626

AR010

EUDRACT 2008-007240-34

NRES 09/S0703/23

Details and patient eligibility

About

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.

Enrollment

77 patients

Sex

All

Ages

18 to 70 years old

Volunteers

Accepts Healthy Volunteers

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