Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000076572
Ethics application status
Approved
Date submitted
14/01/2015
Date registered
29/01/2015
Date last updated
29/01/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
The Effects of One Month of Therapy with the Long-acting Bronchodilator Tiotropium on Small Airway Physiology in Chronic Obstructive Pulmonary Disease
Scientific title
The Effects of One Month of Therapy with the Long-acting Bronchodilator Tiotropium on Ventilation Heterogeneity in Patients with Chronic Obstructive Pulmonary Disease
Secondary ID [1] 285968 0
Nil
Universal Trial Number (UTN)
U1111-1166-0828
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 293900 0
Condition category
Condition code
Respiratory 294208 294208 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will self-administer 18 micrograms tiotropium bromide via oral inhalation route once-daily for 28 +/- 2 days (the precise finish date determined by the availability of the PET scanner). Adherence to therapy will be monitored by drug return and counting
Intervention code [1] 290944 0
Treatment: Drugs
Comparator / control treatment
Participants in the placebo arm will self-administer a placebo capsule via oral inhalation once daily for 28 +/- 2 days (the precise finish date determined by the availability of the PET scanner).
Control group
Placebo

Outcomes
Primary outcome [1] 293993 0
Change in ventilated lung volume, as measured by Galligas PET ventilation scan, following one month of therapy with tiotropium
Timepoint [1] 293993 0
28 +/- 2 days
Secondary outcome [1] 312322 0
Relationship between change in ventilation heterogeneity, measured by Galligas PET ventilation scan, and change in forced oscillation technique (FOT) parameters (resistance and reactance)
Timepoint [1] 312322 0
28 +/- 2 days
Secondary outcome [2] 312323 0
Relationship between change in ventilation heterogeneity, measured by Galligas PET ventilation scan, and change in multiple breath nitrogen washout (MBNW) parameters (lung clearance index, Sacin, Scond)
Timepoint [2] 312323 0
28 +/- 2 days
Secondary outcome [3] 312543 0
Relationship between change in ventilation heterogeneity, measured by Galligas PET ventilation scan, and change in exercise capacity (endurance shuttle walk distance)
Timepoint [3] 312543 0
28 +/-2 days
Secondary outcome [4] 312544 0
Relationship between change in forced oscillation technique (FOT) parameters (resistance and reactance) and change in exercise capacity (endurance shuttle walk distance)
Timepoint [4] 312544 0
28 +/- 2 days
Secondary outcome [5] 312545 0
Relationship between change in MBNW parameters (lung clearance index, Sacin, Scond) and change in exercise capacity (endurance shuttle walk distance)
Timepoint [5] 312545 0
28 +/- 2 days
Secondary outcome [6] 312546 0
Relationship between change in PET ventilation heterogeneity and change in symptom score (St George's Respiratory Questionnaire)
Timepoint [6] 312546 0
28 +/- 2 days
Secondary outcome [7] 312547 0
Relationship between change in FOT parameters and change in symptom score (St George's Respiratory Questionnaire)
Timepoint [7] 312547 0
28 +/- 2 days
Secondary outcome [8] 312548 0
Relationship between change in MBNW parameters and change in symptom score (St George's Respiratory Questionnaire)
Timepoint [8] 312548 0
28 +/- 2 days
Secondary outcome [9] 312549 0
Relationship between change in exercise capacity (endurance shuttle walk distance) and change in symptom score (St George's Respiratory Questionnaire)
Timepoint [9] 312549 0
28 +/- 2 days

Eligibility
Key inclusion criteria
Adults with physician-diagnosed mild-moderate chronic obstructive pulmonary disease, with history of current or past smoking (total exposure > 10 pack years)
Minimum age
50 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Use of tiotropium or any other LAMA or LABA within the previous 4 weeks
* Musculoskeletal (for example, severe arthritis) or other conditions which limit the ability to walk at near-maximal pace
* Significant cardiac disease (ischaemic heart disease or arrhythmia) deemed by the investigators or the subject’s treating cardiologist to make it unsafe for the subject to undertake a supervised near-maximal exercise test
* Documented hypersensitivity to, or intolerance of, anti-cholinergic therapies
* Significant respiratory infection or documented exacerbation of COPD within the previous 6 weeks
* Other active or chronic respiratory pathologies (for example, interstitial lung disease, asthma, chest wall pathology causing ventilatory restriction)
* Past history of lung surgery (including lobectomy or pneumonectomy, but not lung biopsy) or thoracic radiation therapy (excluding isolated mediastinal radiation therapy with no evidence of subsequent pulmonary fibrosis)
* Any major comorbidities deemed to impact on respiratory physiology or symptoms, including severe on uncontrolled heart failure, morbid obesity, muscular or neurological disorders causing respiratory muscle weakness or dysfunctional swallowing
* History of chronic kidney disease (moderate to severe, eGFR less than or equal to 45 mL/min/1.73m2) or severe hepatic impairment
* Unable to perform lung function testing at the enrollment visit
* Dependence on domiciliary supplemental oxygen, unable to go without for at least 1 hour
* Women who are breast feeding, pregnant, or unwilling to avoid pregnancy during the study period
* Unable to provide informed consent
* Current enrolment in other trials

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)
Eligibility determined by the lead investigator and informed consent obtained. Randomisation to the study arm performed by central administration unit who maintains the allocation schedule and dispenses medications according to the allocation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using computer software, in a 2:1 active:placebo ratio
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
* Power calculations are based on previously obtained data from our research group, using SPECT ventilation scanning. This cohort of subjects with COPD had a mean ventilated volume of 61%. We anticipate a 20% increased in mean ventilated volume following therapy with tiotropium. Using a bimean power calculation (at a power of 80% and a significance of 0.05), for a 2:1 (active:placebo) group allocation, the numbers of subjects required to detect this increase are 30 in the active group and 15 in the placebo group.
* The changes in ventilated volume from baseline to end of the study will be measured from the PET/CT images. Differences in mean changes between the active and placebo treated groups will be determined by an unpaired T-test.
* Ventilation in the Galligas PET scans will be measuring using the method of Nagao et al which produces a parameter called the Fractal Dimension. Differences in mean changes in mean fractal dimension between active and placebo treated groups will be determined by an unpaired T-test.
* Relationships between changes in ventilated volume and ventilation heterogeneity in Galligas PET, and changes in FOT parameters, MBNW parameters, exercise capacity (endurance shuttle walk distance) and symptoms scores will be examined by Spearman or Pearson correlations, as appropriate.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/03/2015
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
45
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 3327 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 3328 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 9105 0
2065 - Royal North Shore Hospital
Recruitment postcode(s) [2] 9106 0
2137 - Concord

Funding & Sponsors
Funding source category [1] 290550 0
Charities/Societies/Foundations
Name [1] 290550 0
Woolcock Institute of Medical Research
Country [1] 290550 0
Australia
Funding source category [2] 290551 0
Hospital
Name [2] 290551 0
Royal North Shore Hospital Department of Respiratory and Sleep Medicine
Country [2] 290551 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Woolcock Institute of Medical Research
Address
431 Glebe Point Road,
Glebe NSW 2037
Country
Australia
Secondary sponsor category [1] 289245 0
None
Name [1] 289245 0
Address [1] 289245 0
Country [1] 289245 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292197 0
Northern Sydney Local Health District HREC
Ethics committee address [1] 292197 0
Ethics committee country [1] 292197 0
Australia
Date submitted for ethics approval [1] 292197 0
10/12/2014
Approval date [1] 292197 0
23/12/2014
Ethics approval number [1] 292197 0
HREC/14/HAWKE/388

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

Contacts
Principal investigator
Name 54030 0
A/Prof Greg King
Address 54030 0
Woolcock Institute of Medical Research
431 Glebe Point Road,
Glebe NSW 2037
Country 54030 0
Australia
Phone 54030 0
+61 2 9114 0000
Fax 54030 0
Email 54030 0
[email protected]
Contact person for public queries
Name 54031 0
Stephen Milne
Address 54031 0
Woolcock Institute of Medical Research
431 Glebe Point Road,
Glebe NSW 2037
Country 54031 0
Australia
Phone 54031 0
+61 2 9114 0000
Fax 54031 0
Email 54031 0
[email protected]
Contact person for scientific queries
Name 54032 0
Stephen Milne
Address 54032 0
Woolcock Institute of Medical Research
431 Glebe Point Road,
Glebe NSW 2037
Country 54032 0
Australia
Phone 54032 0
+61 2 9114 0000
Fax 54032 0
Email 54032 0
[email protected]

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

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