Effects of Macrolides on Asthma Control

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo; Drug: Azithromycin

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Gartnavel General Hospital
  • Kilmarnock, United Kingdom, KA2 0BE
    • Crosshouse Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Active treatment.	Drug: Azithromycin; Daily dose 250mg
Placebo Comparator: 2; Placebo control group.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Peak expiratory flow rate.	12 weeks

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Euan J Cameron
• Collaborators: NHS Greater Glasgow and Clyde; University of Glasgow
• Investigators: Principal Investigator: Neil C Thomson, FRCP, University of Glasgow

Publications and helpful links

General Publications

• Thomson NC, Chaudhuri R, Livingston E. Asthma and cigarette smoking. Eur Respir J. 2004 Nov;24(5):822-33. doi: 10.1183/09031936.04.00039004.
• Richeldi L, Ferrara G, Fabbri LM, Lasserson TJ, Gibson PG. Macrolides for chronic asthma. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD002997. doi: 10.1002/14651858.CD002997.pub3.
• Cameron EJ, Chaudhuri R, Mair F, McSharry C, Greenlaw N, Weir CJ, Jolly L, Donnelly I, Gallacher K, Morrison D, Spears M, Evans TJ, Anderson K, Thomson NC. Randomised controlled trial of azithromycin in smokers with asthma. Eur Respir J. 2013 Nov;42(5):1412-5. doi: 10.1183/09031936.00093913. Epub 2013 Sep 13. No abstract available.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: February 26, 2009
• First Submitted That Met QC Criteria: February 26, 2009
• First Posted (Estimate): February 27, 2009

Study Record Updates

• Last Update Posted (Estimate): October 19, 2011
• Last Update Submitted That Met QC Criteria: October 18, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Asthma; Macrolide; Smoker
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: AR010; EUDRACT 2008-007240-34; MRC Grant G0701626; NRES 09/S0703/23

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No