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Trial registered on ANZCTR


Registration number
ACTRN12613000278730
Ethics application status
Approved
Date submitted
4/03/2013
Date registered
8/03/2013
Date last updated
8/03/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Omalizumab for Chronic Allergic Bronchopulmonary Aspergillosis: a randomised, placebo-controlled crossover trial
Scientific title
For patients with chronic allergic bronchopulmonary aspergillosis, does treatment with omalizumab compared to placebo improve clinical symptoms and biological disease markers?
Secondary ID [1] 282059 0
nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Allergic Bronchopulmonary Aspergillosis 288539 0
Condition category
Condition code
Respiratory 288872 288872 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 288873 288873 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Omalizumab 375mg fortnightly subcutaneously for 4 months (8 doses) with a 3-month washout period between omalizumab and placebo arms.
Intervention code [1] 286655 0
Treatment: Drugs
Comparator / control treatment
Normal saline fortnightly subcutaneously (8 doses)
Control group
Placebo

Outcomes
Primary outcome [1] 289000 0
Exacerbations measured by increased symptoms and a significant decrease in lung function and treated by the managing clinicians with escalation of prednisolone dose.
Timepoint [1] 289000 0
4 months
Secondary outcome [1] 301539 0
Symptoms recorded by standardised questions at every visit including the average daily number of puffs of reliever medication over the past week and how many nights in the past week were they woken by asthma symptoms.
Timepoint [1] 301539 0
4 months
Secondary outcome [2] 301540 0
Lung function and exhaled nitric oxide. This was measured by spirometry according to American Thoracic Society recommendations for the performance of spirometry. (American Thoracic Society. Standardization of Spirometry, 1994 Update. Am J Respir Crit Care Med 1995;152:1107-36.) Exhaled nitric oxide was measured in parts per billion using a Medisoft Hypair device, again according to ATS/ERS recommendations. (ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med 2005;171:912-30.)
Timepoint [2] 301540 0
4 months
Secondary outcome [3] 301541 0
Quality of life measured by the Marks Asthma Specific Quality of Life Score (Marks GB, Dunn SM, Woolcock AJ. A scale for the measurement of quality of life in adults with asthma. J Clin Epidemiol 1992;45:461-72.) collected at baseline and end of the 4-month treatment period.
Timepoint [3] 301541 0
4 months
Secondary outcome [4] 301638 0
Flow cytometric analysis of basophils including basophil activation testing using flow cytometric analysis of CD63-stained peripheral blood basophils stimulated with aspergillus fumigatus antigen and controls; determination of basophil FcER1 expression and surface-bound IgE quantitation using labelled anti IgE and anti-FcER1 antibodies.
Timepoint [4] 301638 0
Baseline and 4 month comparison.

Eligibility
Key inclusion criteria
Diagnosis of chronic allergic bronchopulmonary aspergillosis
Symptomatic despite maximal doses of inhaled asthma treatments and regular oral corticosteroids if required.
Previous asthma diagnosis
Elevated serum total IgE (>400kU/L)
Proximal bronchiectasis on CT scan
Detectable specific IgE to Aspergillus antigens
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Recent use of anti-fungal therapy (8 weeks)
Exacerbation requiring increased oral corticosteroid in the past 6 weeks.
Cystic fibrosis
Pregnancy and lactation

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants were patients at a tertiary hospital asthma and allergy clinic. Individuals were informed of the study and invited to participate by attending staff. Once informed consent obtained and enrolled, treatment allocation was performed by the hospital pharmacy who kept the randomisation records and code. Drug or placebo was made up in pharmacy and dispensed to the trial nurse who was blinded to treatment allocation. The nure then administered the treatment. Treating clinicians, lung function and laboratory scientists remained blinded as to the patient's randomisation status.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated code
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
3 month washout between treatment arms when patients received usual treatment.
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Intention to treat with paired analysis, using parametric methods where data was normally distributed or non-parametric equivalents where not. Data analysis conducted using SAS for clinical endpoints or Graphpad for in vitro endpoints.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 708 0
The Alfred - Prahran
Recruitment postcode(s) [1] 6453 0
3181 - Prahran
Recruitment postcode(s) [2] 6454 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 286835 0
Charities/Societies/Foundations
Name [1] 286835 0
Picchi Brothers' Foundation
Address [1] 286835 0
PO Box 7001 Hawthorn North, VIC 3122
Country [1] 286835 0
Australia
Funding source category [2] 286836 0
Commercial sector/Industry
Name [2] 286836 0
Novartis Pharmaceuticals Australia P/L
Address [2] 286836 0
Novartis Pharmaceuticals Australia Pty Limited
54 Waterloo Road
North Ryde NSW 2113
Country [2] 286836 0
Australia
Primary sponsor type
Individual
Name
Jo Douglass
Address
Department of Immunology and Allergy
Royal Melbourne Hospital
Parkville
Melbourne 3050
Victoria
Country
Australia
Secondary sponsor category [1] 285625 0
Individual
Name [1] 285625 0
Dr Andrew Gillman
Address [1] 285625 0
Department of Allergy, Immunology and Respiratory Medicine
Alfred Hospital
Melbourne 3004
Victoria
Country [1] 285625 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288902 0
Alfred Hospital Research and Ethics Committee
Ethics committee address [1] 288902 0
The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria 3004, Australia
Ethics committee country [1] 288902 0
Australia
Date submitted for ethics approval [1] 288902 0
11/08/2008
Approval date [1] 288902 0
30/10/2008
Ethics approval number [1] 288902 0
273/08

Summary
Brief summary
The aim of this study was to conduct a pilot randomised study into the efficacy of omalizumab in allergic bronchopulmonary aspergillosis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 38262 0
Dr Andrew Gillman
Address 38262 0
Department of Allergy, Immunology and Respiratory Medicine
Alfred Hospital
Melbourne 3004
Victoria
Country 38262 0
Australia
Phone 38262 0
+61 3 90762934
Fax 38262 0
+61 3 90762245
Email 38262 0
a.gillman@alfred.org.au
Contact person for public queries
Name 38263 0
Dr Andrew Gillman
Address 38263 0
Department of Allergy, Immunology and Respiratory Medicine
Alfred Hospital
Melbourne 3004
Victoria
Country 38263 0
Australia
Phone 38263 0
+61 3 90762934
Fax 38263 0
Email 38263 0
a.gillman@alfred.org.au
Contact person for scientific queries
Name 38264 0
Dr Andrew Gillman
Address 38264 0
Department of Allergy, Immunology and Respiratory Medicine
Alfred Hospital
Melbourne 3004
Victoria
Country 38264 0
Australia
Phone 38264 0
+61 3 90762934
Fax 38264 0
Email 38264 0
a.gillman@alfred.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary