Effects of Macrolides on Asthma Control

NCT ID: NCT00852579

Last Updated: 2011-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2011-08-31

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Active treatment.

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

Daily dose 250mg

2

Placebo control group.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Azithromycin

Daily dose 250mg

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Glasgow

OTHER

Sponsor Role: collaborator

NHS Greater Glasgow and Clyde

OTHER

Sponsor Role: collaborator

Euan J Cameron

OTHER

Sponsor Role: lead

Responsible Party

Euan J Cameron

Clinical Research Fellow - Respiratory Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Neil C Thomson, FRCP

Role: PRINCIPAL_INVESTIGATOR

University of Glasgow

Locations

Gartnavel General Hospital

Glasgow, , United Kingdom

Crosshouse Hospital

Kilmarnock, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 15516679 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16235309 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24036246 (View on PubMed)

Other Identifiers

EUDRACT 2008-007240-34

Identifier Type: -

Identifier Source: secondary_id

MRC Grant G0701626

Identifier Type: -

Identifier Source: secondary_id

NRES 09/S0703/23

Identifier Type: -

Identifier Source: secondary_id

AR010

Identifier Type: -

Identifier Source: org_study_id