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Trial registered on ANZCTR


Registration number
ACTRN12615000389505
Ethics application status
Approved
Date submitted
30/12/2014
Date registered
28/04/2015
Date last updated
28/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised double blind study to investigate the effect of oxygen versus air driven nebulisers on partial pressure of arterial carbon dioxide in patients with an exacerbation of chronic obstructive pulmonary disease.
Scientific title
In patients with an exacerbation of chronic obstructive pulmonary disease, a comparison between the effect of air versus oxygen driven nebulisers on the partial pressure of carbon dioxide.
Secondary ID [1] 285879 0
Nil
Universal Trial Number (UTN)
U111111634438
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease (COPD) 293800 0
Condition category
Condition code
Respiratory 294103 294103 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oxygen driven nebuliser regimen (all administered on a single occasion):
a. t=0-15 min: 2.5 mg salbutamol by nebulisation, delivered by oxygen at a flow rate of 8L/min
b. t=15-20 min: Removal of nebuliser mask
c. t=20-35 min: 2.5 mg salbutamol by nebulisation, delivered by oxygen at a flow rate of 8L/min.
Intervention code [1] 290860 0
Treatment: Other
Comparator / control treatment
Air driven nebuliser regimen (all administered on a single occasion):
a. t=0-15 min: 2.5 mg salbutamol by nebulisation, delivered by air at a flow rate of 8L/min
b. t=15-20 min: Removal of nebuliser mask
c. t=20-35 min: 2.5 mg salbutamol by nebulisation, delivered by air at a flow rate of 8L/min.
Control group
Active

Outcomes
Primary outcome [1] 293896 0
PtCO2 (transcutaneous CO2) at t=35min*, adjusted for baseline.
Timepoint [1] 293896 0
At t=35min

*or the last recorded measurement should the t=35 measurement not be obtained (e.g. study terminated early due to a rise in PtCO2 greater than or equal to 10mmHg).
Secondary outcome [1] 312106 0
pH (Fingertip or earlobe capillary blood gas sample) immediately prior to t=35min, adjusted for baseline.
Timepoint [1] 312106 0
immediately prior to t=35 min
Secondary outcome [2] 312107 0
PtCO2 (transcutaneous carbon dioxide) at six minutes after the initiation of the first and second nebulisers (t=6 min and t=26 min). PtCO2 is measured through the skin via a transcutaneous monitor.
Timepoint [2] 312107 0
At six minutes after the initiation of the first and second nebulisers (t=6 min and t=26 min)
Secondary outcome [3] 312108 0
PtCO2 at 5 minute intervals from t=0 to t=80 min. Measured via transcutaneous monitoring.
Timepoint [3] 312108 0
At 5 minute intervals from t=0 to t=80 min
Secondary outcome [4] 312109 0
Proportion of participants with greater than or equal to 4mmHg (physiologically significant) increase in PcapCO2 from baseline, measured by capillary blood gas.
Timepoint [4] 312109 0
Comparison between measure at baseline and t=35 min.
Secondary outcome [5] 312110 0
Number of intervention terminations due to a rise in transcutaneous carbon dioxide level (PtCO2) greater than or equal to 10mmHg. PtCO2 is measured by transcutaneous monitor.
Timepoint [5] 312110 0
From baseline up to t=35.
Secondary outcome [6] 312111 0
The proportion of patients with a reduction in pH of greater than or equal to 0.06 from baseline. pH is measured using capillary blood gas.
Timepoint [6] 312111 0
Comparison between measure at baseline and t=35 min.
Secondary outcome [7] 312112 0
Proportion of patients who required initiation of an increase in the flow of oxygen therapy during the regimen and observation periods.
Timepoint [7] 312112 0
The regimen (t=0 to t=35min) and observation periods (t=35 to t=80 min).
Secondary outcome [8] 312392 0
SpO2 at 5 minute intervals from t=0 to t=80 min. Measured via pulse oximetry.
Timepoint [8] 312392 0
At 5 minute intervals from t=0 to t=80 min
Secondary outcome [9] 312393 0
Heart rate at 5 minute intervals from t=0 to t=80 min. Measured via transcutaneous monitoring.
Timepoint [9] 312393 0
At 5 minute intervals from t=0 to t=80 min
Secondary outcome [10] 312394 0
Proportion of participants with greater than or equal to 8mmHg (clinically significant) increase in PcapCO2 from baseline, measured by capillary blood gas.
Timepoint [10] 312394 0
Comparison between measure at baseline and t=35 min.
Secondary outcome [11] 312395 0
Proportion of participants with greater than or equal to 4mmHg (physiologically significant) increase in PtCO2 from baseline, measured by transcutaneous monitor.
Timepoint [11] 312395 0
Comparison between measure at baseline and during subsequent intervention (up to t=35 min).
Secondary outcome [12] 312396 0
Proportion of participants with greater than or equal to 8mmHg (clinically significant) increase in PtCO2 from baseline, measured by transcutaneous monitor.
Timepoint [12] 312396 0
Comparison between measure at baseline and during subsequent intervention (up to t=35 min).
Secondary outcome [13] 316540 0
PcapCO2 (fingertip or earlobe capillary gas sample) at completion of the second nebulisation (immediately prior to t=35min*), adjusted for baseline PcapCO2.
Timepoint [13] 316540 0
immediately prior to t=35min
Secondary outcome [14] 316541 0
Greatest PtCO2 change from baseline at any of the recorded time points between t=0 and t=35 minutes when the nebuliser is in place
Timepoint [14] 316541 0
t=5, 6, 10, 15, 25, 26, 30, 35 minutes

Eligibility
Key inclusion criteria
i. Ninety patients admitted to Hutt Valley or Wellington Regional Hospital medical inpatient wards with a primary admission diagnosis of an exacerbation of COPD.
ii. Participants must have the mental capacity to allow them to provide written informed consent.
Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i. Age <40 years at time of randomisation
ii. Requirement for assisted non-invasive ventilation at time of randomisation
iii. Baseline PtCO2 >60mmHg at time of randomisation
iv. Requirement for greater than or equal to 4L/min of oxygen via nasal cannulae to maintain SpO2 between 88-92% prior to or during titration
v. Any other condition which, at the investigator’s discretion, is believed may present a safety risk or impact the feasibility of the study or the study results (including pregnancy or breastfeeding).

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)
Potentially eligible participants will be identified on the wards and invited to take part in the study. Patients can be recruited at any time during their medical admission; however the study visit should be timed to deliver the nebuliser regimen as close as possible to the time of the next prescribed bronchodilator dose. Written Informed consent will take place prior to any study specific procedures. The allocated intervention will be stored in an opaque sealed envelope and opened at the time of randomisation by the un-blinded investigator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be 1:1 via a block randomised computer generated sequence, provided by the study statistician independent of recruitment and assessment of participants. Participants recruited will be stratified in to groups that were receiving oxygen immediately prior to randomisation or those that were not.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
Analysis will be by intention to treat. Our primary analysis is ANCOVA with PtCO2 as the response variable, and randomised treatment and baseline PtCO2 as co-variates. For other continuous outcome variables we will also use similar ANCOVA. Exploratory analyses for PtCO2, heart rate and SpO2 taken at five minute intervals will be presented graphically and analysed by mixed linear models.

SAMPLE SIZE
A difference in PaCO2 of 4 mmHg represents a physiologically significant change. In our controlled study of oxygen versus air driven nebulisers in stable COPD (Edwards et al) the standard deviation of PtCO2 was 5.5. With 90% power and alpha of 5% this requires a total of 82 patients to detect a 4 mmHg difference. We anticipate a drop-out rate of <10% so our target recruitment is 90 patients.

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 outside Australia
Country [1] 6561 0
New Zealand
State/province [1] 6561 0
Wellington

Funding & Sponsors
Funding source category [1] 290461 0
Government body
Name [1] 290461 0
Heath Research Council of New Zealand
Address [1] 290461 0
Level 3 - ProCARE Building, Grafton Mews, at 110 Stanley Street, Auckland 1010
Country [1] 290461 0
New Zealand
Funding source category [2] 290462 0
Charities/Societies/Foundations
Name [2] 290462 0
Medical Research Institute of New Zealand
Address [2] 290462 0
Wellington Regional Hospital,
Riddiford Street,
Newtown,
Wellington 6021
Country [2] 290462 0
New Zealand
Primary sponsor type
Individual
Name
Professor Richard Beasley
Address
MRINZ,
Wellington Regional Hospital,
Riddiford Street,
Newtown,
Wellington 6021
Country
New Zealand
Secondary sponsor category [1] 289163 0
None
Name [1] 289163 0
Address [1] 289163 0
Country [1] 289163 0
Other collaborator category [1] 278272 0
Individual
Name [1] 278272 0
Dr Janine Pilcher
Address [1] 278272 0
MRINZ,
Wellington Regional Hospital,
Riddiford Street,
Newtown,
Wellington 6021
Country [1] 278272 0
New Zealand
Other collaborator category [2] 278273 0
Individual
Name [2] 278273 0
Dr George Bardsley
Address [2] 278273 0
MRINZ,
Wellington Regional Hospital,
Riddiford Street,
Newtown,
Wellington 6021
Country [2] 278273 0
New Zealand
Other collaborator category [3] 278437 0
Individual
Name [3] 278437 0
Dr Steven McKinstry
Address [3] 278437 0
MRINZ,
Wellington Regional Hospital,
Riddiford Street,
Newtown,
Wellington 6021
Country [3] 278437 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292134 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 292134 0
Health and Disability Ethics Committees
Ministry of Health
C/- MEDSAFE, Level 6, Deloitte House
10 Brandon Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 292134 0
New Zealand
Date submitted for ethics approval [1] 292134 0
Approval date [1] 292134 0
09/12/2014
Ethics approval number [1] 292134 0
14/NTB/200

Summary
Brief summary
A parallel group double blinded randomised controlled trial comparing the effect of air versus oxygen driven bronchodilator nebulisation on PaCO2, pH and oxygen saturation (SpO2) in patients admitted to hospital with an acute exacerbation of COPD. Ninety patients will be recruited and randomised to receive two 15 minute administrations of salbutamol by nebulisation, delivered by air or oxygen at a flow rate of 8L/min
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 53670 0
Dr George Bardsley
Address 53670 0
MRINZ, Wellington Regional Hospital, Riddiford Street, Newtown, Wellington 6021
Country 53670 0
New Zealand
Phone 53670 0
+64 4 8050241
Fax 53670 0
+64 4 3895707
Email 53670 0
george.bardsley@mrinz.ac.nz
Contact person for public queries
Name 53671 0
Dr George Bardsley
Address 53671 0
MRINZ, Wellington Regional Hospital, Riddiford Street, Newtown, Wellington 6021
Country 53671 0
New Zealand
Phone 53671 0
+64 4 8050241
Fax 53671 0
+64 4 3895707
Email 53671 0
george.bardsley@mrinz.ac.nz
Contact person for scientific queries
Name 53672 0
Dr George Bardsley
Address 53672 0
MRINZ, Wellington Regional Hospital, Riddiford Street, Newtown, Wellington 6021
Country 53672 0
New Zealand
Phone 53672 0
+64 4 8050241
Fax 53672 0
+64 4 3895707
Email 53672 0
george.bardsley@mrinz.ac.nz

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