AZISAST Study: AZIthromycin in Severe ASThma Study

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00760838

Acronym

AZISAST

Enrollment

109

Registered

2008-09-26

Start date

2009-03-31

Completion date

2011-09-30

Last updated

2014-06-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

Inadequately controlled severe asthma

Brief summary

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.

Interventions

DRUGAzithromycin 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

DRUGPlacebo

Placebo three times a week during treatment period (6 months); run-in period of 2 weeks; wash-out period of 4 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Proportion of Participants With Severe Asthma Exacerbations	from baseline to week 26	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.

Secondary

Measure	Time frame	Description
Proportion of Participants Using Rescue Medication From Baseline to Week 26	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.
Peakflow Measurements	from baseline to week 26	change in peak expiratory volume peak expiratory volume is measured as a maximal expiration for 1 second
Change in Forced Expiratory Volume in 1 Second	from baseline to week 26	—
Change in Total Score on Asthma Control Questionnaire (ACQ)	from baseline to week 26	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).
Change in Total Score on the Asthma-related Quality of Life (AQLQ)	from baseline to week 26	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.

Countries

Belgium

Participant flow

Participants by arm

Arm	Count
Placebo Placebo 1x/day during 5 days 3x/week afterwards	54
Azithromycin Azithromycin 250 mg 1x/day during 5 days 3x/week afterwards	55
Total	109

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	1
Overall Study	Lack of Efficacy	1	0
Overall Study	Lost to Follow-up	2	0
Overall Study	Withdrawal by Subject	1	1

Baseline characteristics

Characteristic	Azithromycin	Placebo	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	55 Participants	54 Participants	109 Participants
Age, Continuous	53 years	53 years	53 years
Region of Enrollment Belgium	55 participants	54 participants	109 participants
Sex: Female, Male Female	29 Participants	38 Participants	67 Participants
Sex: Female, Male Male	26 Participants	16 Participants	42 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	39 / 54	37 / 55
serious Total, serious adverse events	4 / 54	7 / 55

Outcome results

Primary

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.

Time frame: from baseline to week 26