AZISAST Study: AZIthromycin in Severe ASThma Study

• Sponsor: University Hospital, Ghent (Other)
• Overall Status: Completed
• CT.gov ID: NCT00760838
• Collaborator: Agentschap voor Innovatie door Wetenschap en Technologie (Other)
• Enrollment: 109
• Locations: 7
• Arms: 2
• Duration (Months): 30
• Patients Per Site: 15.6
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Azithromycin 250 mg; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 109 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. Peakflow Measurements [from baseline to week 26]

   change in peak expiratory volume peak expiratory volume is measured as a maximal expiration for 1 second

3. Change in Forced Expiratory Volume in 1 Second [from baseline to week 26]

4. 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).

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Onze Lieve Vrouw Ziekenhuis Aalst	Aalst		Belgium	9300
2	ZNA Middelheim	Antwerpen		Belgium	2020
3	AZ Sint-Jan Brugge	Brugge		Belgium	8000
4	Ghent University Hospital	Ghent		Belgium	9000
5	AZ Groeninge	Kortrijk		Belgium	8500
6	Universitair Ziekenhuis Leuven	Leuven		Belgium	3000
7	AZ Heilig Hart Roeselare	Roeselare		Belgium	8800

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Guy Brusselle, MD, PhD, University Hospital, Ghent

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Website of the Ghent University Hospital

Publications

None provided.

• Responsible Party: University Hospital, Ghent
• ClinicalTrials.gov Identifier: NCT00760838
• Other Study ID Numbers: 2008/445; IWT 070709
• First Posted: Sep 26, 2008
• Last Update Posted: Jun 26, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by University Hospital, Ghent: Inadequately controlled severe asthma
• Additional relevant MeSH terms: Asthma; Azithromycin

Study Results

Participant Flow

Arm/Group Title	Placebo	Azithromycin
Arm/Group Description	Placebo 1x/day during 5 days 3x/week afterwards	Azithromycin 250 mg 1x/day during 5 days 3x/week afterwards
Period Title: Overall Study
STARTED	54	55
COMPLETED	49	53
NOT COMPLETED	5	2

Baseline Characteristics

Arm/Group Title	Placebo	Azithromycin	Total
Arm/Group Description	Placebo 1x/day during 5 days 3x/week afterwards	Azithromycin 250 mg 1x/day during 5 days 3x/week afterwards	Total of all reporting groups
Overall Participants	54	55	109
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	54 100%	55 100%	109 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	53	53	53
Sex: Female, Male (Count of Participants)
Female	38 70.4%	29 52.7%	67 61.5%
Male	16 29.6%	26 47.3%	42 38.5%
Region of Enrollment (participants) [Number]
Belgium	54 100%	55 100%	109 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants With Severe Asthma Exacerbations
Description	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

Outcome Measure Data

Analysis Population Description

intention to treat analysis

Arm/Group Title	Placebo	Azithromycin
Arm/Group Description	Placebo 1x/day during 5 days 3x/week afterwards	Azithromycin 250 mg 1x/day during 5 days 3x/week afterwards
Measure Participants	54	55
Mean (95% Confidence Interval) [proportion of participants]	0.52 1%	0.55 1%

2. Secondary Outcome

Title	Proportion of Participants Using Rescue Medication From Baseline to Week 26
Description	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.
Time Frame	from baseline to week 26

Outcome Measure Data

Analysis Population Description

intention to treat analysis

Arm/Group Title	Placebo	Azithromycin
Arm/Group Description	Placebo 1x/day during 5 days 3x/week afterwards	Azithromycin 250 mg 1x/day during 5 days 3x/week afterwards
Measure Participants	54	55
Mean (Standard Deviation) [proportion of participants]	0.24 (2.11) 0.4%	0.08 (1.14) 0.1%

3. Secondary Outcome

Title	Peakflow Measurements
Description	change in peak expiratory volume peak expiratory volume is measured as a maximal expiration for 1 second
Time Frame	from baseline to week 26

Outcome Measure Data

Analysis Population Description

intention to treat analysis

Arm/Group Title	Placebo	Azithromycin
Arm/Group Description	Placebo 1x/day during 5 days 3x/week afterwards	Azithromycin 250 mg 1x/day during 5 days 3x/week afterwards
Measure Participants	54	55
morning Peak Expiratory Volume	-5.77 (48.20)	-1.81 (54.27)
evening Peak Expiratory Volume	-4.65 (78.68)	-0.81 (48.47)

4. Secondary Outcome

Title	Change in Forced Expiratory Volume in 1 Second
Time Frame	from baseline to week 26

Outcome Measure Data

Analysis Population Description

intention to treat analysis

Arm/Group Title	Placebo	Azithromycin
Arm/Group Description	Placebo 1x/day during 5 days 3x/week afterwards	Azithromycin 250 mg 1x/day during 5 days 3x/week afterwards
Measure Participants	54	55
pre-bronchodilatator FEV1	-0.90 (11.79)	-0.02 (10.06)
post-bronchodilatator FEV1	-0.66 (1.29)	8.84 (12.50)

5. Secondary Outcome

Title	Change in Total Score on Asthma Control Questionnaire (ACQ)
Description	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).
Time Frame	from baseline to week 26

Outcome Measure Data

Analysis Population Description

intention to treat analysis

Arm/Group Title	Placebo	Azithromycin
Arm/Group Description	Placebo 1x/day during 5 days 3x/week afterwards	Azithromycin 250 mg 1x/day during 5 days 3x/week afterwards
Measure Participants	54	55
Mean (Standard Deviation) [units on a scale]	-0.12 (0.70)	-0.24 (0.93)

6. Secondary Outcome

Title	Change in Total Score on the Asthma-related Quality of Life (AQLQ)
Description	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.
Time Frame	from baseline to week 26

Outcome Measure Data

Analysis Population Description

intention to treat analysis

Arm/Group Title	Placebo	Azithromycin
Arm/Group Description	Placebo 1x/day during 5 days 3x/week afterwards	Azithromycin 250 mg 1x/day during 5 days 3x/week afterwards
Measure Participants	54	55
Mean (Standard Deviation) [units on a scale]	0.20 (0.73)	0.32 (0.89)

Adverse Events

Time Frame	from randomisation to exit visit (during the whole study period, at least 24 weeks)
Arm/Group Title	Placebo		Azithromycin
Arm/Group Description	Placebo 1x/day during 5 days 3x/week afterwards		Azithromycin 250 mg 1x/day during 5 days 3x/week afterwards
All Cause Mortality
	Placebo		Azithromycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Azithromycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/54 (7.4%)		7/55 (12.7%)
Blood and lymphatic system disorders
deep venous trombosis	0/54 (0%)	0	1/55 (1.8%)	0
cerebrovascular accident	0/54 (0%)		1/55 (1.8%)
Cardiac disorders
acute myocardial infarction	1/54 (1.9%)		0/55 (0%)
Gastrointestinal disorders
gastro-enteritis	0/54 (0%)		1/55 (1.8%)
oesophagitis grade A	0/54 (0%)		1/55 (1.8%)
Musculoskeletal and connective tissue disorders
pseudoparalysis right shoulder	0/54 (0%)		1/55 (1.8%)
Respiratory, thoracic and mediastinal disorders
asthma exacerbation	2/54 (3.7%)		3/55 (5.5%)
pneumonia	1/54 (1.9%)		0/55 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Azithromycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/54 (72.2%)		37/55 (67.3%)
Blood and lymphatic system disorders
thrombocytopenia	0/54 (0%)		1/55 (1.8%)	1
leucopenia	0/54 (0%)		1/55 (1.8%)	1
Gastrointestinal disorders
nausea	2/54 (3.7%)	2	1/55 (1.8%)	1
diarrhea	7/54 (13%)	8	3/55 (5.5%)	3
abdominal pain	6/54 (11.1%)	8	2/55 (3.6%)	2
Hepatobiliary disorders
elevated liver function event	0/54 (0%)		2/55 (3.6%)	2
Immune system disorders
allergic reaction	1/54 (1.9%)	1	2/55 (3.6%)	2
Nervous system disorders
headache	3/54 (5.6%)	3	3/55 (5.5%)	4
vertigo	1/54 (1.9%)	1	2/55 (3.6%)	2
Respiratory, thoracic and mediastinal disorders
lower respiratory tract infection	22/54 (40.7%)	34	17/55 (30.9%)	24
asthma exacerbation	27/54 (50%)	41	26/55 (47.3%)	40

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.