Phenotype based management of severe persistent asthma

Not Applicable

• Conditions: Severe persistent asthma; Respiratory - Asthma; Inflammatory and Immune System - Other inflammatory or immune system disorders

• Registration Number: ACTRN12612000807853
• Lead Sponsor: John Hunter Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-08-02
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

Diagnosed with severe persistent asthma defined as uncontrolled asthma which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity including impaired lung function) on maximal treatment with inhaled corticosteroid and long-acting Beta2-agonist
-Confirmed variable airflow obstruction at screening visit or documented within the past 10 years
-Bronchodilator response >200ml OR > 12% (post-bronchodilator FEV1 following administration of 400mcg salbutamol, pMDI with spacer; after 10 minutes, or following administration of nebulised ventolin)
-Airway hyperresponsiveness (in response to any standard challenge agent)
-Peak flow variability >12%
-FEV1 variability > 12%
-If not observed, then hypertonic saline challenge at visit 1 (pD15 < 15mL saline).
-Aged >18 years.

Exclusion Criteria

-Aged < 18 years.
-Treatment with any macrolide or tetracycline 4 weeks prior to screening.
-Treatment with oral corticosteroids 4 weeks prior to screening (unless a low dose is being taken on a long-term basis: 10mg for >3 months)
-Hypersensitivity to macrolides
-Prolonged QTc > 0.44s at screening or during treatment
-Taking medication that will interact with azithromycin in regard to QTc prolongation
-Existing ECG abnormalities that may lead to arrhythmias
-Pregnancy/breast feeding, likely to become pregnant or unwilling to use an additional form of contraception for the first 2 months of treatment if taking the oral contraceptive pill
-Diagnosed with respiratory disease other than severe persistent asthma or bronchiectasis (e.g. active tuberculosis, pulmonary fibrosis) OR diagnosed with coexisting respiratory disease that, at investigator’s discretion, would adversely impact on study conduct.
-Current lung cancer or other blood, lymphatic or solid organ malignancy
-Inability to attend study visits
-Impaired liver function at screening as shown by AST, ALT, alkaline phosphatase or total bilirubin > 1.5 times the upper limit of normal (During treatment if > 2 times the upper limit of normal)
-Impaired renal function at screening as shown by Creatinine Clearance < 30mL/min
-Ocular surgery within 3 months of study entry
-Abdominal, chest or brain surgery within 3 months
-Known cerebral, aortic, or abdominal aneurysm
-Females of child-bearing potential, not using reliable contraception or unwilling to use a second method of contraception during the first 2 months of treatment if taking the oral contraceptive pill
-Participants who have participated in another investigative drug study parallel to, or within 4 weeks of study entry

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Health related quality of life as measured by the Juniper Asthma Quality of Life Questionnaire.[At baseline and week 16 following completion of study.]

Secondary Outcome Measures

Name	Time	Method
Systemic inflammatory markers (CRP, IL-6) measured by ELISA[Baseline and week 16];Airway inflammation measured by sputum cell counts[Baseline and week 16];Asthma control measured by Juniper Asthma Control Questionnaire[Baseline and week 16];Lung function measured by spirometry (Medgraphics CPFS/D instrumentation, Minnesota, USA)[Baseline and week 16];Sputum gene expression (by qPCR) of targets previously associated with severe persistent asthma, including MMP9 and members of the p38 signalling pathway measured by quantitative polymerase chain reaction.[Baseline and week 16];Body composition measured by dual energy xray absorptiometry[Baseline and week 16];Exercise capacity will be assessed using the 6 minute walk test[baseline and week 16]