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Trial registered on ANZCTR


Registration number
ACTRN12617001275358
Ethics application status
Approved
Date submitted
17/08/2017
Date registered
5/09/2017
Date last updated
5/09/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Can Functional Lung Ventilation Imaging in Asthma and Chronic obstructive pulmonary disease identify response to treatment.
Scientific title
Can functional lung ventilation imaging identify treatable traits in obstructive airway disease?
Secondary ID [1] 292672 0
nil known
Universal Trial Number (UTN)
Trial acronym
ITT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe asthma 304417 0
Chronic obstructive pulmonary disease 304418 0
Condition category
Condition code
Respiratory 303746 303746 0 0
Asthma
Respiratory 303747 303747 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Functional lung ventilation imaging with quantification using Technegas will be used. Tomographic pulmonary scintigraphy (ventilation/perfusion single photon emission computed tomography: V/P SPECT) is a nuclear medicine investigation that gives a 3dimensional functional map of the ventilation and perfusion of the lungs and shows how these are affected by disease. The participant will breathe in a very small amount of nanoparticle suspension for ventilation images and be given an injection of radioactive material, called Technetium99mTc, for the perfusion images. The VQ scan takes less than an hour. A low radiation CT scan will also be performed as part of the imaging.
All 100 participants will undergo the baseline imaging. A subgroup of 30 participants will receive a second imaging session after 12 weeks of add-on therapy. This treatment will be part of their current clinical practice at the John Hunter Hospital Respiratory Clinic, under the supervision of the patient’s treating physician.
Participants in the sub-group will receive either Mepolizumab, Omalizumab or Macrolide antibiotics. Mepolizumab is administered by subcutaneous injection of 150mg every 4 weeks. Omalizumab will also be administered by subcutaneous injections every 2 weeks or 4 weeks with the patient's pre-treatment serum total IgE level (IU/mL) and body weight (lb or kg) being used to determine doses (mg) and dosing frequency. The dosing table can be found at: https://www.xolair.com/allergic-asthma/hcp/determining-the-dose.html.. Macrolide antibiotics will be administered as oral azithromycin as either 250mg daily or 500mg, 3 times per week depending on the patient's preference and perceived adherence.
The overall time-frame of each add-on therapy may vary between participants, however the second imaging scan will happen after they have undergone 12 weeks of their treatment.
Medication adherence will be routinely assessed by respiratory nurses and clinicians at each clinic review by open ended questions. Adherence will also be checked by the clinical research assistant at the 12-week follow-up study visit.
Intervention code [1] 298907 0
Diagnosis / Prognosis
Intervention code [2] 298944 0
Treatment: Devices
Intervention code [3] 299020 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 303117 0
Ventilation heterogeneity among patients with severe obstructive airways diseases as assessed using technegas functional lung ventilation and perfusion with imaging and quantification
Timepoint [1] 303117 0
0 weeks (all participants)
Primary outcome [2] 303169 0
Technegas functional lung ventilation and perfusion imaging quantification responsiveness to change following intervention in patients with severe obstructive airways diseases.

Timepoint [2] 303169 0
12 weeks (30 participants)
Secondary outcome [1] 337915 0
ACQ score
Timepoint [1] 337915 0
0 weeks (all participants) and 12 weeks (30 participants)

Eligibility
Key inclusion criteria
Adults (greater than or equal to 18 years) with severe treatment refractory asthma defined according to ATS/ERS criteria:
-Asthma which requires treatment with guidelines-suggested medications for GINA steps 4-5 (high dose ICS and LABA or leukotriene modifier/theophylline) for the previous year or systemic corticosteroids for greater than or equal to 50% of the previous year to prevent it from becoming “uncontrolled” or which remains “uncontrolled” despite this therapy
-Uncontrolled asthma defined as at least one of the following:
*Poor symptom control: ACQ consistently > 1.5, ACT < 20
*Frequent severe exacerbations: 2 or more bursts of systemic corticosteroids (greater than 3 days each) in the previous year
*Serious exacerbations: at least one hospitalisation, ICU stay or mechanical ventilation in the previous year
*Airflow limitation: after appropriate bronchodilator withhold FEV1 < 80% predicted (in the face of reduced FEV1/FVC defined as less than the lower limit of normal)
OR
Adults (greater than or equal to 18 years) with obstructive airways disease (either asthma or COPD) who are to be treated with add on therapies (macrolides, monoclonal antibody therapies or itraconazole). This includes moderate or severe asthma or COPD, with persistent symptoms, and/or frequent exacerbations. Exacerbations will be defined as indicated below.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
•Inability to attend study visits.
•Current lung cancer or other blood, lymphatic or solid organ malignancy
•Diagnosis with primary respiratory disease other than asthma or COPD (e.g. active tuberculosis, pulmonary fibrosis)
•Expected prognosis poor <3 months survival
•Pregnancy or breast-feeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
A cross-sectional analytic design will be used to assess baseline imaging sessions in all participants. A before-after clinical trial will be used to assess a subgroup of participants at a second imaging session after they undergoes a standard treatment as part of routine clinical practice.
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
Summary statistics will be reported for the cross sectional characterisation study. Parametric results will be reported as mean (SD) and non-parametric results as median (q1,q3).
To compare differences in before and after treatment responses of continuous variables, we will perform Students¹ paired t-tests for parametric data and the two-sample Wilcoxon Rank Sum for non parametric data, and the Chi-squared or Fisher¹s exact test for categorical variables. Associations will be determined using Pearson¹s or Spearman¹s correlation coefficients as appropriate.
Results will reported as significant when p<0.05.

Recruitment
Recruitment status
Not yet recruiting
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)
NSW
Recruitment hospital [1] 8849 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 16998 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 297312 0
Commercial sector/Industry
Name [1] 297312 0
Cyclopharm Limited
Address [1] 297312 0
Unit 4, The Crescent Kingsgrove, NSW 2208
Country [1] 297312 0
Australia
Primary sponsor type
Individual
Name
Vanessa McDonald
Address
Level 2, Hunter Medical Research Institute
1 Kookaburra Circuit, New Lambton Heights NSW 2305
Country
Australia
Secondary sponsor category [1] 296282 0
None
Name [1] 296282 0
Address [1] 296282 0
Country [1] 296282 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298417 0
Hunter New England Human Research Ethics
Ethics committee address [1] 298417 0
Lookout Road, New Lambton Heights, NSW 2208
Ethics committee country [1] 298417 0
Australia
Date submitted for ethics approval [1] 298417 0
14/12/2016
Approval date [1] 298417 0
07/04/2017
Ethics approval number [1] 298417 0
16/12/14/4.02

Summary
Brief summary
Chronic Obstructive Pulmonary Disease and Severe Asthma are chronic obstructive airway diseases associated with a high disease burden. They are complex diseases that can be complicated by significant comorbidity. A new and emerging approach to these conditions is to focus on the identification and treatment of the processes that underlie individual disease. These components are termed ‘treatable traits’.
An important aspect of the treatable traits approach is objective monitoring to select and continue therapy. Most current monitoring approaches are assessed using nonobjective
measures, that do not capture improvements after treatment.
Functional lung ventilation imaging with quantification using Technegas may address this clinical need. Tomographic pulmonary scintigraphy (ventilation/perfusion single photon emission computed tomography: V/P SPECT) is a nuclear medicine investigation that gives a 3dimensional functional map of the ventilation and perfusion of the lungs and shows how these are affected by disease.
We believe that this new imaging approach may be a useful objective measure of disease and treatment response in severe asthma and COPD.
In the current study, we aim to quantify:
1. Whether functional lung ventilation technology can objectively quantify ventilation heterogeneity in patients with severe obstructive airway disease (asthma or COPD).
2. Determine whether functional lung ventilation imaging can be used to quantify response to therapies.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77018 0
Prof Vanessa McDonald
Address 77018 0
Level 2, Hunter Medical Research Institute
1 Kookaburra Circuit, New Lambton Heights NSW 2305
Country 77018 0
Australia
Phone 77018 0
+61 2 4042 0146
Fax 77018 0
+61 2 4042 0046
Email 77018 0
vanessa.mcdonald@newcastle.edu.au
Contact person for public queries
Name 77019 0
Miss Gabrielle LeBrocq
Address 77019 0
Level 2, Hunter Medical Research Institute
1 Kookaburra Circuit, New Lambton Heights NSW 2305
Country 77019 0
Australia
Phone 77019 0
+61 2 4042 0131
Fax 77019 0
+61 2 4042 0046
Email 77019 0
gabrielle.lebrocq@newcastle.edu.au
Contact person for scientific queries
Name 77020 0
Prof Peter Gibson
Address 77020 0
John Hunter Hospital, Respiratory and Sleep Medicine
Locked Bag 1, HMRC NSW 2310
Country 77020 0
Australia
Phone 77020 0
+61 2 4042 0143
Fax 77020 0
+61 2 4042 0046
Email 77020 0
peter.gibson@hnehealth.nsw.gov.au

No data has been provided for results reporting
Summary results
Not applicable