Effect of macrolides on asthma control, airway inflammation and bacterial colonisation in smokers with asthma - Macrolide Asthma Study

Phase 1

• Conditions: asthma; MedDRA version: 9.1 Level: LLT Classification code 10003553 Term: Asthma; MedDRA version: 9.1 Level: PT Classification code 10003553 Term: Asthma

• Registration Number: EUCTR2008-007240-34-GB
• Lead Sponsor: HS Greater Glasgow & Clyde Hospitals & University of Glasgow

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-04-16
• Study Completion: 2011-08-03
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 80

Inclusion Criteria

Inclusion criteria

1. Diagnosis of asthma: Typical symptoms [episodic wheezing, chest tightness and/or dyspnoea] And either reversible airflow obstruction (> 12% and 200 ml change in FEV1 with nebulised salbutamol 2.5 mg) at any study visit prior to randomisation
or methacholine airway hyperresponsiveness [20% drop in FEV1 at a concentration of methacholine = 8 mg/ml].
2. Age range 18-70 years [subjects above the age of 60 should have had asthma symptoms starting before the age of 40]
3. Duration of asthma symptoms > 1 year and on stable medication for 4 weeks
4. Able to maintain asthma without exacerbations at BTS step 2 level (beclometasone dose of 400 mcg/day and salbutamol as required) during the run-in period of the study.
5. Able to wean off other asthma medication, other than inhaled corticosteroid and short acting bronchodilator in the two weeks prior to the screening visit.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion criteria
1. Ex-smokers or never smokers
2. Planning to quit smoking during duration of trial
3. Patients with unstable asthma; defined as the presence of 1 or more of the following events in the month prior to randomisation [Emergency/’out of hours’ visit of patients to the GP; GP visit to patient at home; A & E hospital attendance; hospital admission].
4. Patients with current epilepsy, psychosis or history of significant atrial or ventricular tachyarrhythmia.
5. Corrected QT-interval greater than 450 msec in women and greater than 430 msec in men on baseline electrocardiogram (ECG).
6. Low potassium levels [less than normal values for the laboratory]. If low potassium can be corrected, screening can continue with confirmation of normal levels prior to taking study medication.
7. Liver disease (alanine transaminase and/or aspartate transaminase levels 2 or more times the upper limit of normal).
8. Significant renal disease: creatinine or urea levels 2 or more times the upper limit of normal.
9. Any previous severe adverse reaction to macrolides.
10. Patients who are known to have specific IgE sensitivity or skin test positivity to grass pollen allergen and a history of worsening of asthma due to hay fever, will not be recruited from mid May to the end of July (grass allergen season in UK).
11. 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.
12. Patients who require medications known to interact with azithromycin including:
- anti-psychotics, including Reboxitine and Quetiapine
- antivirals, including Nelfinavir, Zidovudine, Didanosine
- bromocriptine
- carbergoline
- clozapine
- coumarin-Type Oral Anticoagulants including warfarin
- cyclosporin
- ergot derivatives
- itraconazole
- midazolam
- mizolastine
- moxifloxacin
- rifamycins
- theophylline
- vinblastine

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Main Objective: This randomised controlled trial will test the hypothesis that macrolides improve asthma control and reduce sputum neutrophil counts of smokers with chronic asthma.<br><br><br> Primary Morning Peak Expiratory Flow after 12 wks of treatment<br> ;<br> Secondary Objective: Secondary end points:<br> - Average of the last 7 days PEF measurements before each visit from the home recordings, with 3 being the minimum number of evaluable days.<br> - spirometry<br> - airway responsiveness to methacholine<br> - asthma control score<br> - cough score<br> - sputum cell counts<br> - diary symptom scores<br> - Exhaled Nitric Oxide<br> - exacerbation rates<br> ;Primary end point(s): Change in morning peak expiratory flow (PEF)