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Trial registered on ANZCTR


Registration number
ACTRN12618000075280
Ethics application status
Approved
Date submitted
29/12/2017
Date registered
18/01/2018
Date last updated
18/01/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Exploring the impact of chronic obstructive pulmonary disease (COPD) patient characteristics on inhaler device capability and inhaler device characteristics on treatment efficacy.
Scientific title
Does limited inspiratory capacity in severe COPD impair clinical efficacy of breath-actuated inhaled medication?
Secondary ID [1] 293695 0
Nil known
Universal Trial Number (UTN)
U1111-1207-0649
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COPD 306024 0
Condition category
Condition code
Respiratory 305176 305176 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part of the trial is observational and part interventional.
Observational component: measurement of baseline characteristics at the start of a hospital admission for COPD exacerbation and assessing inhaler technique on admission and again at 6 weeks
Interventional component: the trial is single blind (investigator), randomised cross-over trial. Stable, severe COPD patients are randomised to a sequence of inhaler devices (starting with Accuhaler or metered dose inhaler/spacer) delivering the same dose of medication (fluticasone propionate/salmeterol xinafoate SFC 500/50mcg, twice daily). The Accuhaler (also marketed as Diskus) is a round-shaped inhaler that the patient's often liken to a "spaceship" in appearance. The metered dose inhaler is the most commonly used "puffer" type recognised in the lay community. The Accuhaler is a type of dry powder inhaler (DPI) and is breath-actuated. For breath-actuated devices, the patient must generate sufficient inspiratory flow to overcome the intrinsic device resistance for effective actuation and drug deposition. Inherent resistance, and hence inspiratory flow requirement, varies by device. For the metered dose inhaler actuation is part of the device's own function and so this device is much less dependent on inspiratory flow rates. However, for this device, the coordination of actuation and inhalation is critical, and this problem can be largely overcome by using a volumatic spacer or "spacer". Hence, for both devices inhaler technique is important but for the Accuhaler, the patient must generate sufficient inspiratory flow to overcome the device's intrinsic resistance.
After each of two consecutive six week exposure periods study outcomes are assessed. There is no washout between the two treatment exposures (the medication used in each treatment exposure is identical - the treatment exposure differ only in terms of the device used). The primary outcome is quality of life score via the Saint George Respiratory Questionnaire and secondary outcomes include exercise endurance (via the six minute walk test) and complex lung function testing. Treatment adherence is not formally assessed in this study, although inhaler technique, an aspect of treatment adherence, is assessed at baseline and prior to each six week exposure period.
Intervention code [1] 299947 0
Treatment: Devices
Intervention code [2] 300018 0
Treatment: Drugs
Comparator / control treatment
The observational component is uncontrolled.
The interventional component is a cross over study - subjects act as their own controls, as they sequence through the two device interventions
Control group
Active

Outcomes
Primary outcome [1] 304332 0
Quality of life score via Saint George Respiratory Questionnaire (total score)
Timepoint [1] 304332 0
Assessed at baseline, 6 and 12 weeks post randomisation
Secondary outcome [1] 341610 0
Six minute walk test distance
Timepoint [1] 341610 0
Assessed at baseline, 6 and 12 weeks post randomisation
Secondary outcome [2] 341611 0
Forced expiratory volume in one second - using spirometry
Timepoint [2] 341611 0
Assessed at baseline, 6 and 12 weeks post randomisation
Secondary outcome [3] 341901 0
Forced vital capacity, assessed using spirometry
Timepoint [3] 341901 0
Assessed at baseline, 6 and 12 weeks post randomisation
Secondary outcome [4] 341903 0
Inspiratory muscle strength, assessed using measurement of maximal inspiratory pressure (MIP). MIP was measured using standard lung function testing equipment according to American Thoracic Society/ European Respiratory Society guidelines published in 2002. The lung function testing equipment is not solely used for measurement of MIP (eg also used for plethysmography, spirometry) but the most relevant components include a mouthpiece, a pressure transducer (to record the maximal generated inspiratory pressure) and a "closed" circuit with a small amount of incorporated leak (to prevent falsely low recordings due to unintentional glottic closure by the subject).
Timepoint [4] 341903 0
Assessed at baseline, 6 and 12 weeks post randomisation
Secondary outcome [5] 341904 0
residual volume, assessed using plethysmography
Timepoint [5] 341904 0
Assessed at baseline, 6 and 12 weeks post randomisation

Eligibility
Key inclusion criteria
Age 40 or more years, moderate to severe COPD diagnosed clinically and on spirometry
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
COPD exacerbation within 6 weeks
psychosocial circumstances or physical health preventing informed consent or completion of study protocol

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)
allocation contained within sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation - recruitment target set and the same number of opaque sealed envelopes prepared, half containing one sequence allocation and half containing the alternate sequence allocation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
There were no precedent studies on which to base sample size estimations for powering this study prior to commencement, as most pharmaceutical trials comparing efficacy had compared medications rather than devices and had seldom used outcomes other than lung function. During planning phase, published studies reporting statistically significant lung function outcomes for device comparisons, cited sample sizes of 10-21 subjects. Hence, subject recruitment target was set at 40; 20 subjects in each grouping.

To handle problems with missing data, we performed multiple imputation using the multivariate normal imputation (MVNI) approach. We assumed arbitrary missingness as the missing data mechanism showed a mixture of monotone and non-monotone missingness. Using imputations, we performed repeated measures ANOVA in order to estimate the effects of exposure to inhaler devices (Accuhaler versus MDI/s), inhaler techniques (adequate versus inadequate) and study inclusion group on the outcome variables. We used imputed datasets to perform repeated measures ANCOVA to estimate the effect of baseline lung function on the study’s outcome measures. T-tests were used to test the significance of each. The ANOVA and ANCOVA results were finally pooled using Rubin’s method. All models were adjusted for period effect, sequence effect and subject(sequence) effect. The effect size for exposure to inhaler devices or inhaler technique was estimated as the mean difference of the dependent variable between the category whose effect was assessed and the category whose effect was not.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
15/11/2009
Date of last participant enrolment
Anticipated
Actual
11/03/2015
Date of last data collection
Anticipated
Actual
3/06/2015
Sample size
Target
40
Accrual to date
Final
28
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 9648 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [2] 9649 0
Camden Hospital - Camden
Recruitment postcode(s) [1] 18412 0
2560 - Campbelltown
Recruitment postcode(s) [2] 18413 0
2570 - Camden

Funding & Sponsors
Funding source category [1] 298312 0
Charities/Societies/Foundations
Name [1] 298312 0
Royal Australasian College of Physicians
Country [1] 298312 0
Australia
Funding source category [2] 298313 0
University
Name [2] 298313 0
Western Sydney University
Country [2] 298313 0
Australia
Primary sponsor type
Hospital
Name
Campbelltown Hospital
Address
Therry Rd.,
Campbelltown
NSW 2560
Country
Australia
Secondary sponsor category [1] 297425 0
University
Name [1] 297425 0
western Sydney University
Address [1] 297425 0
Narellen and Gilchrist Dr.,
Campbelltown
NSW 2560
Country [1] 297425 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299308 0
South Western Sydney Local Health District Human Reseach Ethics Committee
Ethics committee address [1] 299308 0
Ethics committee country [1] 299308 0
Australia
Date submitted for ethics approval [1] 299308 0
15/03/2009
Approval date [1] 299308 0
15/10/2009
Ethics approval number [1] 299308 0
HREC/09/LPOOL/15

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

Contacts
Principal investigator
Name 79998 0
Dr Belinda Cochrane
Address 79998 0
Campbelltown Hospital
PO box 149
Campbelltown
NSW 2560
Country 79998 0
Australia
Phone 79998 0
+61 2 46344001
Fax 79998 0
+61 2 46344011
Email 79998 0
belindacochrane@bigpond.com
Contact person for public queries
Name 79999 0
Belinda Cochrane
Address 79999 0
Campbelltown Hospital
PO Box 149
Campbelltown
NSW 2560
Country 79999 0
Australia
Phone 79999 0
+61 2 46344001
Fax 79999 0
+61 2 46344011
Email 79999 0
belindacochrane@bigpond.com
Contact person for scientific queries
Name 80000 0
Belinda Cochrane
Address 80000 0
Campbelltown Hospital
PO Box 149
Campbelltown
NSW 2560
Country 80000 0
Australia
Phone 80000 0
+61 2 46344001
Fax 80000 0
+61 2 46344011
Email 80000 0
belindacochrane@bigpond.com

No information has been provided regarding IPD availability


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
SourceTitleYear of PublicationDOI
EmbaseDoes device matter for inhaled therapies in advanced chronic obstructive pulmonary disease (COPD)? A comparative trial of two devices.2019https://dx.doi.org/10.1186/s13104-019-4123-5
N.B. These documents automatically identified may not have been verified by the study sponsor.