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Trial registered on ANZCTR


Registration number
ACTRN12607000155493
Ethics application status
Approved
Date submitted
27/02/2007
Date registered
6/03/2007
Date last updated
6/03/2007
Type of registration
Retrospectively registered

Titles & IDs
Public title
Is Dornase alfa (Pulmozyme ) effective if administered at night, in relation to airways clearance techniques? A multi centre, crossover, randomised controlled trial for people with cystic fibrosis.
Scientific title
Is Dornase alfa (Pulmozyme ) effective if administered at night, in relation to airways clearance techniques? A multi centre, crossover, randomised controlled trial for people with cystic fibrosis.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis (CF) 1657 0
Condition category
Condition code
Human Genetics and Inherited Disorders 1762 1762 0 0
Cystic fibrosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following randomisation to determine morning or evening Dornase alfa (rhDNase, [Pulmozyme]) administration as commencement intervention, paediatric and adult CF outpatients were studied over a six week period: 14 day regimes of morning or evening rhDNase administration, with 14 days washout between the two regimes. These regimes resulted in alteration of the interval time between rhDNase nebulisation and chest physiotherapy. The subject’s usual routine for chest physiotherapy and exercise were unaltered. Outcomes were measured at start and end of each regime when participants attended four study visits (each approximately 30-60 minutes’ duration). The subjects were all current users of nebulised rhDNase (2.5mg unit dose ampoule nebulised once daily via Pari LC+ nebuliser; duration approximately 10 minutes); the study protocol required alteration of the time of day or night at which rhDNase was administered to alter the in-situ dwell time of rhDNase in relation to chest physiotherapy.
Usual timing of rhDNase administration in relation to chest physiotherapy is highly variable, with "short" intervals in some users (eg 15 minutes prior to physiotherapy) and others having a "long" interval (eg 8-10 hours if rhDNase is taken at night). Patients acted as their own control, using their "usual" timing during the washout period of 14 days, and data was analysed with consideration of "usual" in-situ dwell time of rhDNase compared to longer or shorter intervals caused by the study protocol.
Intervention code [1] 1619 0
Treatment: Other
Comparator / control treatment
Control group
Active

Outcomes
Primary outcome [1] 2459 0
Spirometry: Forced Expiratory Volume in one second (FEV1). The washout period was day 15 to 28 in all participants, during which they returned to their "usual" timing of rhDNase nebulisation.
Timepoint [1] 2459 0
Measured at baseline, 14 days, 28 days, and 42 days.
Primary outcome [2] 2460 0
Spirometry: Forced Vital Capacity (FVC). The washout period was day 15 to 28 in all participants, during which they returned to their "usual" timing of rhDNase nebulisation.
Timepoint [2] 2460 0
Measured at baseline, 14 days, 28 days, and 42 days.
Primary outcome [3] 2461 0
Spirometry: Forced expiratory Flow Rate between 25 and 75% of FVC (FEF25-75%). The washout period was day 15 to 28 in all participants, during which they returned to their "usual" timing of rhDNase nebulisation.
Timepoint [3] 2461 0
Measured at baseline, 14 days, 28 days, and 42 days.
Primary outcome [4] 2462 0
Spirometry: Sputum weight (gm) collected from the preceding day's chest physiotherapy session/s. The washout period was day 15 to 28 in all participants, during which they returned to their "usual" timing of rhDNase nebulisation.
Timepoint [4] 2462 0
Measured at baseline, 14 days, 28 days, and 42 days.
Primary outcome [5] 2463 0
Spirometry: CF-specific quality of life via cystic fibrosis questionnaire-revised (CFQ-R). The washout period was day 15 to 28 in all participants, during which they returned to their "usual" timing of rhDNase nebulisation.
Timepoint [5] 2463 0
Measured at baseline, 14 days, 28 days, and 42 days.
Secondary outcome [1] 4226 0
Additional outcomes were subjective cough score via Verbal Category Descriptive Score(VCD) and medication adherence (returned empty rhDNase nebules).
Timepoint [1] 4226 0
All outcomes were measured at baseline, 14 days, 28 days, and 42 days. The washout period was day 15 to 28 in all participants, during which they returned to their "usual" timing of rhDNase nebulisation.

Eligibility
Key inclusion criteria
With CF attending outpatient clinics; using rhDNase (Pulmozyme); able to perform spirometry; with stable lung disease as assessed by physician at the time of the study; not currently participating in another clinical trial. Stable lung disease was defined as no deterioration in symptoms and no change in chest management for one month (Henry et al, 1998). Patients were excluded if they were currently enrolled in another study or had significant comorbidities (eg unstable diabetes).
Minimum age
5 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

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 concealment (sealed opaque envelopes)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random number tables on Excel
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
The physiotherapist and research assistant assessing outcomes were blinded to the time of day at which the subject was receiving nebulised rhDNase. After all data had been collected, the randomisation envelope was opened to allow analysis based on timing at each 14 day block of the study.
Phase
Phase 4
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis

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)

Funding & Sponsors
Funding source category [1] 1914 0
Commercial sector/Industry
Name [1] 1914 0
Roche Products Australia
Address [1] 1914 0
Country [1] 1914 0
Australia
Primary sponsor type
Hospital
Name
Royal Children's Hospital
Address
Country
Australia
Secondary sponsor category [1] 1726 0
Individual
Name [1] 1726 0
Anne Chang
Address [1] 1726 0
Country [1] 1726 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 3558 0
Royal Children's Hospital Brisbane
Ethics committee address [1] 3558 0
Ethics committee country [1] 3558 0
Australia
Date submitted for ethics approval [1] 3558 0
Approval date [1] 3558 0
04/02/2003
Ethics approval number [1] 3558 0
Ethics committee name [2] 3559 0
Mater Adult Hospital Brisbane
Ethics committee address [2] 3559 0
Ethics committee country [2] 3559 0
Australia
Date submitted for ethics approval [2] 3559 0
Approval date [2] 3559 0
16/04/2003
Ethics approval number [2] 3559 0
566A,
Ethics committee name [3] 3560 0
Gold Coast Hospital, Southport
Ethics committee address [3] 3560 0
Ethics committee country [3] 3560 0
Australia
Date submitted for ethics approval [3] 3560 0
Approval date [3] 3560 0
31/07/2003
Ethics approval number [3] 3560 0
200334
Ethics committee name [4] 3561 0
The Prince Charles Hospital Brisbane
Ethics committee address [4] 3561 0
Ethics committee country [4] 3561 0
Australia
Date submitted for ethics approval [4] 3561 0
Approval date [4] 3561 0
17/11/2004
Ethics approval number [4] 3561 0
EC2460

Summary
Brief summary
The aim of this study was to investigate if a longer time interval between rhDNase nebulisation and chest physiotherapy improves clinical outcomes of subjects with CF.

METHODS: A single-blind randomised cross-over trial was conducted on subjects with CF from outpatients of 4 hospitals. Subjects were in stable health and studied over 6-weeks (utilising 14-day blocks of morning or evening rhDNase administration with 14-days washout). Usual regimes for physiotherapy and exercise were unaltered. Thus changing the times altered the dwell time of rhDNase prior to physiotherapy. Long interval was defined as dwell time of >6-hours and short as <6-hours. Outcomes were measured at pre and post each regime.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27553 0
Address 27553 0
Country 27553 0
Phone 27553 0
Fax 27553 0
Email 27553 0
Contact person for public queries
Name 10808 0
Christine Wilson
Address 10808 0
Physiotherapy Department
Royal Children's Hospital
Herston Rd
Brisbane QLD 4029
Country 10808 0
Australia
Phone 10808 0
+61 7 36368506
Fax 10808 0
+61 7 36365181
Email 10808 0
christine_wilson@health.qld.gov.au
Contact person for scientific queries
Name 1736 0
Christine Wilson
Address 1736 0
Physiotherapy Department
Royal Children's Hospital
Herston Rd
Brisbane QLD 4029
Country 1736 0
Australia
Phone 1736 0
+61 7 36368506
Fax 1736 0
+61 7 36365181
Email 1736 0
christine_wilson@health.qld.gov.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