Effects of Macrolides on Asthma Control

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00852579
• Other study ID #: AR010
• Secondary ID: EUDRACT 2008-007
• Status: Completed
• Phase: Phase 3
• First received: February 26, 2009
• Last updated: October 18, 2011
• Start date: March 2009
• Est. completion date: August 2011

Study information

• Verified date: October 2011
• Source: University of Glasgow
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Azithromycin
Daily dose 250mg
• Placebo
Placebo

Locations

Country	Name	City	State
United Kingdom	Gartnavel General Hospital	Glasgow
United Kingdom	Crosshouse Hospital	Kilmarnock

Sponsors (3)

Lead Sponsor	Collaborator
Euan J Cameron	NHS Greater Glasgow and Clyde, University of Glasgow

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

Richeldi L, Ferrara G, Fabbri LM, Lasserson TJ, Gibson PG. Macrolides for chronic asthma. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD002997. Review. Update in: Cochrane Database Syst Rev. 2015;9:CD002997. — View Citation

Thomson NC, Chaudhuri R, Livingston E. Asthma and cigarette smoking. Eur Respir J. 2004 Nov;24(5):822-33. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak expiratory flow rate.		12 weeks	No
Secondary	Spirometry		12 weeks	No
Secondary	Asthma control score		12 weeks	No
Secondary	Average of last 7 days PEF measurements		12 weeks	No
Secondary	Sputum cell counts		12 weeks	No
Secondary	Fraction of expired nitric oxide		12 weeks	No
Secondary	Airway responsiveness to methacholine		12 weeks	No
Secondary	Exacerbation rates		12 weeks	No
Secondary	Cough score		12 weeks	No
Secondary	Diary symptom score		12 weeks	No