AZISAST Study: AZIthromycin in Severe ASThma Study (AZISAST)

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Azithromycin 250 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • Onze Lieve Vrouw Ziekenhuis Aalst
  • Antwerpen, Belgium, 2020
    • ZNA Middelheim
  • Brugge, Belgium, 8000
    • AZ Sint-Jan Brugge
  • Ghent, Belgium, 9000
    • Ghent University Hospital
  • Kortrijk, Belgium, 8500
    • AZ Groeninge
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven
  • Roeselare, Belgium, 8800
    • AZ Heilig Hart Roeselare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. patients who have given written informed consent
2. males or females of any race
3. 18-75 years of age
4. with the diagnosis of persistent asthma ≥ 1 year duration at screening and a history consistent with GINA step 4 or 5 clinical features
5. receiving high dose ICS plus inhaled LABA for at least 6 months prior to screening
6. patients who have suffered multiple (i.e. at least two) independent documented severe asthma exacerbations within the previous 12 months
7. patients must be never-smokers or ex-smokers with a smoking history of ≤ 10 pack-years.

Exclusion Criteria:

1. females who are pregnant or who are breastfeeding
2. patients with severe bronchiectasis
3. patients with active tuberculosis or non-tuberculous mycobacterial infections (NTM)
4. 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
5. who are unable to perform spirometry or complete a patient diary or complete questionnaires
6. patients with known hypersensitivity to azithromycin or other macrolide antibiotics
7. patients who's heart rate corrected QT interval is prolonged
8. patients who have - in the judgement of the investigator - a clinically relevant laboratory abnormality
9. patients currently treated with macrolide antibiotics or recent macrolide treatment (in the past twelve weeks)
10. anti-IgE treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: Agentschap voor Innovatie door Wetenschap en Technologie

Publications and helpful links

General Publications

• Undela K, Goldsmith L, Kew KM, Ferrara G. Macrolides versus placebo for chronic asthma. Cochrane Database Syst Rev. 2021 Nov 22;11(11):CD002997. doi: 10.1002/14651858.CD002997.pub5.
• Brusselle GG, Vanderstichele C, Jordens P, Deman R, Slabbynck H, Ringoet V, Verleden G, Demedts IK, Verhamme K, Delporte A, Demeyere B, Claeys G, Boelens J, Padalko E, Verschakelen J, Van Maele G, Deschepper E, Joos GF. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax. 2013 Apr;68(4):322-9. doi: 10.1136/thoraxjnl-2012-202698. Epub 2013 Jan 3.

Helpful Links

• Website of the Ghent University Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: September 25, 2008
• First Submitted That Met QC Criteria: September 25, 2008
• First Posted (Estimate): September 26, 2008

Study Record Updates

• Last Update Posted (Estimate): June 26, 2014
• Last Update Submitted That Met QC Criteria: June 25, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Inadequately controlled severe asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: 2008/445; IWT 070709