AZISAST Study: AZIthromycin in Severe ASThma Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety and cost-effectiveness of azithromycin as add-on therapy in adult subjects with severe persistent asthma, who remain inadequately controlled despite GINA (2006) step 4 or 5 therapy.

Official Title
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The AZIthromycin in Severe ASThma (AZISAST) Study: a Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Evaluating the Efficacy, Safety and Cost-effectiveness of Azithromycin as add-on Therapy in Adult Subjects With Severe Persistent Asthma, Who Remain Inadequately Controlled Despite GINA (2006) Step 4 or 5 Therapy

Conditions
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Asthma

Intervention / Treatment
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* Drug: Azithromycin 250 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients who have given written informed consent males or females of any race 18-75 years of age with the diagnosis of persistent asthma ≥ 1 year duration at screening and a history consistent with GINA step 4 or 5 clinical features receiving high dose ICS plus inhaled LABA for at least 6 months prior to screening patients who have suffered multiple (i.e. at least two) independent documented severe asthma exacerbations within the previous 12 months patients must be never-smokers or ex-smokers with a smoking history of ≤ 10 pack-years. Exclusion Criteria: females who are pregnant or who are breastfeeding patients with severe bronchiectasis patients with active tuberculosis or non-tuberculous mycobacterial infections (NTM) patients with significant underlying medical conditions (e.g. infection, hematological disease, malignancy, neurologic, renal, hepatic, coronary heart disease or other cardiovascular disease, endocrinologic or gastrointestinal disease) within the previous 3 months who are unable to perform spirometry or complete a patient diary or complete questionnaires patients with known hypersensitivity to azithromycin or other macrolide antibiotics patients who's heart rate corrected QT interval is prolonged patients who have - in the judgement of the investigator - a clinically relevant laboratory abnormality patients currently treated with macrolide antibiotics or recent macrolide treatment (in the past twelve weeks) anti-IgE treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azithromycin<br>Azithromycin 250 mg 1x/day during 5 days 3x/week afterwards | Drug: Azithromycin 250 mg<br>* Azithromycin 250 mg three times a week during treatment period (6 months); run-in period of 2 weeks; wash-out period of 4 weeks<br>|
| Placebo Comparator: placebo<br>Placebo 1x/day during 5 days 3x/week afterwards | Drug: Placebo<br>* Placebo three times a week during treatment period (6 months); run-in period of 2 weeks; wash-out period of 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Severe Asthma Exacerbations | Severe asthma exacerbations are defined as severe asthma episodes for which a treatment with antibiotics or cortisone is administered for a minimum of 3 days. | from baseline to week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Using Rescue Medication From Baseline to Week 26 | proportion of participants using rescue medication is defined as the the number of participants who had to use rescue medication from baseline untill week 26, independent on the number of times the medication had to be used. This measure was conducted by averaging the proportion of participants using rescue medication from each week between baseline and week 26. | from baseline to week 26 | 
| Peakflow Measurements | change in peak expiratory volume peak expiratory volume is measured as a maximal expiration for 1 second | from baseline to week 26 | 
| Change in Forced Expiratory Volume in 1 Second |  | from baseline to week 26 | 
| Change in Total Score on Asthma Control Questionnaire (ACQ) | A simple questionnaire to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or as a result of treatment. ACQ has a multidimensional construct assessing symptoms (5 items--self-administred) and rescue inbronchodilator use (1 item-self-administered), and FEV1% (1 item) completed by clinic staff Scaling of items: 7-point scale (0=no impairment, 6= maximum impairment for symptoms and rescue use; and 7 categories for FEV1%) Scores range between 0 (totally controlled) and 6 (severely uncontrolled). | from baseline to week 26 | 
| Change in Total Score on the Asthma-related Quality of Life (AQLQ) | A disease-specific health-related quality of life instrument that taps both physical and emotional impact of disease 32 items with 2-week recall: Symptoms (11 items), Activity Limitation (12 items, 5 of which are individualized), Emotional Function (5 items), and Environmental Exposure (4 items) 7-point Likert scale (7 = not impaired at all - 1 = severely impaired). Scores range 1-7, with higher scores indicating better quality of life. | from baseline to week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inadequately controlled severe asthma