Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000395336
Ethics application status
Approved
Date submitted
6/03/2017
Date registered
17/03/2017
Date last updated
16/03/2020
Date data sharing statement initially provided
20/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the effectiveness of nebulised Pulmozyme (dornase alfa) in reducing inflammation in chronic airway disease
Scientific title
Targeting neutrophil extracellular traps with dornase alfa to reduce inflammation in chronic airway disease
Secondary ID [1] 291054 0
Nil known
Universal Trial Number (UTN)
U1111-1192-7504
Trial acronym
NETs
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic airway disease 301848 0
Chronic Obstructive Pulmonary Disease (COPD) 302454 0
Asthma 302455 0
Condition category
Condition code
Respiratory 301527 301527 0 0
Chronic obstructive pulmonary disease
Respiratory 301528 301528 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will attend a screening visit (V1) to assess airway inflammation, and if eligible, a randomisation visit 2 weeks later (V2), All participants deemed eligible for the study, will receive both dornase alfa as well as the placebo medication, which will both be administered via nebulisation. The order in which each medication is received will be randomised and the participant will not be aware of which medication they are receiving at each timepoint. The participant will be randomly allocated to receive either dornase alfa via nebuliser (Pulmozyme, 2.5mg) or placebo, once daily for 10 days. The first treatment sequence will be a period of 10 days (visit 2/3), followed by a 2 week washout period (return for visit 4) and concluding with the second 10 day treatment sequence (visit 5). Participants will be contacted via telephone call midway (Day 5) through each treatment period, to monitor adherence. To further monitor adherence, participants will also be asked to complete a diary and to return all drug ampules (used and unused).
Intervention code [1] 297042 0
Treatment: Drugs
Comparator / control treatment
The placebo consists of a solution containing 0.9% w/v Sodium Chloride (table salt) in water which will be administered using a nebuliser. In this study we will use a placebo as a control in testing the new treatment option. A control is used to minimise the effects of any factors other than the active drug so that we can conclude whether or not the results of our trial are due to the active drug only. In this study each participant will receive both the active medication (Pulmozyme) as well as the placebo, at different time points. The order of this will be randomly allocated.
Control group
Placebo

Outcomes
Primary outcome [1] 300934 0
The primary outcome is the level of extracellular DNA in sputum (picogreen assay)
Timepoint [1] 300934 0
Outcomes will be measured at baseline, at the start and completion of each treatment sequence.
Primary outcome [2] 301448 0
The detection of neutrophil extracellular traps (NETs) using immunofluorescent staining of sputum smears
Timepoint [2] 301448 0
Outcomes will be measured at baseline, at the start and completion of each treatment sequence.
Secondary outcome [1] 331232 0
Lung function including FEV1 and FEV1/FVC
Timepoint [1] 331232 0
Outcomes will be measured at baseline, at the start and completion of each treatment sequence
Secondary outcome [2] 331233 0
Health related quality of life will be assessed by the Juniper Asthma Quality of Life Questionnaire (AQLQ)
Timepoint [2] 331233 0
Outcomes will be measured at baseline, at the start and completion of each treatment sequence
Secondary outcome [3] 331234 0
Asthma symptoms will be assessed by the Juniper asthma control questionnaire (ACQ) aswell as the Juniper asthma quality of life questionnaire (AQLQ).
Timepoint [3] 331234 0
Outcomes will be measured at baseline, at the start and completion of each treatment sequence and midway through the treatment phase (day 5)
Secondary outcome [4] 331237 0
Mucous hypersecretion will be assessed by study specific questionnaire
Timepoint [4] 331237 0
Outcomes will be measured at baseline, at the start and completion of each treatment sequence and midway through each treatment (day 5).
Secondary outcome [5] 331238 0
Antimicrobial proteins (LL-37 and a-defensins) will be assessed by enzyme linked immunosorbent assay (ELISA) and sputum supernatant.
Timepoint [5] 331238 0
Outcomes will be measured at baseline, at the start and completion of each treatment sequence
Secondary outcome [6] 331239 0
Proteases (neutrophil elastase and MMP-9) will be assessed by enzyme linked immunosorbent assay (ELISA) and sputum supernatant.
Timepoint [6] 331239 0
Outcomes will be measured at baseline, at the start and completion of each treatment sequence
Secondary outcome [7] 331240 0
Airway inflammation will be assessed by differential cell counts of sputum inflammatory cells. Sputum will be obtained by induction during hypertonic saline challenge.
Timepoint [7] 331240 0
Outcomes will be measured at baseline, at the start and completion of each treatment sequence
Secondary outcome [8] 332699 0
COPD symptoms will be assessed by the COPD assessment test (CAT) and the St George Respiratory Questionnaire (SGRQ)
Timepoint [8] 332699 0
Outcomes will be measured at baseline, at the start and completion of each treatment sequence and midway through the treatment phase (day 5)
Secondary outcome [9] 332700 0
Exacerbation frequency will be assessed by study specific questionnaire
Timepoint [9] 332700 0
Outcomes will be measured at baseline, at the start and completion of each treatment sequence and midway through the treatment phase (day 5)
Secondary outcome [10] 332701 0
Medication use will be assessed by study specific questionnaire
Timepoint [10] 332701 0
Outcomes will be measured at baseline, at the start and completion of each treatment sequence and midway through the treatment phase (day 5)

Eligibility
Key inclusion criteria
Males and females aged >18 years with Doctor diagnosed stable COPD, confirmed by incompletely reversible airflow obstruction (post bronchodilator FEV1<80% predicted and FEV1/FVC<70%)
Males and females aged >18 years with Doctor diagnosed stable asthma
Non-smokers or ex-smokers (> 6 months since last cigarette).
High levels of sputum NETs (>20ng/uL eDNA, conducted in Aim 1) (determined after screening visit)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
COPD or asthma exacerbation or respiratory tract infection (OCS or antibiotics), or change in maintenance therapy in the past 6 weeks (visit will be postponed)
Current smoking (last 6 months)
Any use of antibiotics in the past month (visit will be postponed)
Pregnancy or breastfeeding
Inability to attend clinic visits
Other significant illness likely to interfere with management or participation in the study
Participation in any other interventional research study in the last 4 weeks

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)
This study is a double blind crossover study, employing concealed random allocation. Allocation concealment will be achieved as randomisation will be done by an independent statistician. Each participant will receive both the active treatment (Pulmozyme) as well as the placebo treatment, at different time points. The order in which each treatment is completed is randomly allocated; the assessors and the participants will not be aware of which treatment the participant is receiving during each treatment period.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Concealed random allocation will be employed. Randomisation will be done by an
independent statistician using computer-generated codes, in blocks of variable size, stratifying for gender and age.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
In our pilot data, the level of eDNA when log transformed was normally distributed with a standard deviation of 1.97. To detect a change in matched pairs of eDNA equivalent to 1 standard deviation (1.97), we will need to study 10 subjects per group (asthma and COPD) to be able to reject the null hypothesis that the response difference is 0 with 80% power and a=0.05. For this proof of concept study we will randomise 15 asthma and 15 COPD subjects to account for drop outs of failed sample collection.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/04/2017
Actual
22/06/2017
Date of last participant enrolment
Anticipated
31/12/2019
Actual
13/12/2019
Date of last data collection
Anticipated
31/12/2019
Actual
8/01/2020
Sample size
Target
30
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7422 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 15227 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 295493 0
Charities/Societies/Foundations
Name [1] 295493 0
Lung Foundation of Australia
Country [1] 295493 0
Australia
Funding source category [2] 295495 0
Hospital
Name [2] 295495 0
John Hunter Hospital
Country [2] 295495 0
Australia
Funding source category [3] 295847 0
Government body
Name [3] 295847 0
NHMRC
Country [3] 295847 0
Australia
Primary sponsor type
University
Name
University of Newcastle
Address
University Drive Callaghan NSW 2308
Country
Australia
Secondary sponsor category [1] 294707 0
None
Name [1] 294707 0
Address [1] 294707 0
Country [1] 294707 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296821 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 296821 0
Ethics committee country [1] 296821 0
Australia
Date submitted for ethics approval [1] 296821 0
26/02/2015
Approval date [1] 296821 0
20/04/2015
Ethics approval number [1] 296821 0
15/03/18/3.04

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72134 0
Dr Katherine Baines
Address 72134 0
Hunter Medical Research Institute
Lot 1 Kookaburra Circuit
New Lambton Heights, NSW 2305
Country 72134 0
Australia
Phone 72134 0
+61 2 40420090
Fax 72134 0
+61 2 40420046
Email 72134 0
[email protected]
Contact person for public queries
Name 72135 0
Penelope Chan
Address 72135 0
Hunter Medical Research Institute
Lot 1 Kookaburra Circuit
New Lambton Heights, NSW 2305
Country 72135 0
Australia
Phone 72135 0
+61 2 40420122
Fax 72135 0
+61 2 40420046
Email 72135 0
[email protected]
Contact person for scientific queries
Name 72136 0
Katherine Baines
Address 72136 0
Hunter Medical Research Institute
Lot 1 Kookaburra Circuit
New Lambton Heights, NSW 2305
Country 72136 0
Australia
Phone 72136 0
+61 2 40420090
Fax 72136 0
+61 2 40420046
Email 72136 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not ethics approved for sharing of data


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.