Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000752662
Ethics application status
Approved
Date submitted
20/06/2014
Date registered
16/07/2014
Date last updated
24/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Personal best exhaled nitric oxide on oral versus inhaled corticosteroid in chronic obstructive pulmonary disease
Scientific title
In COPD patients, is personal best exhaled nitric oxide lower on oral or inhaled corticosteroid?
Secondary ID [1] 284828 0
None
Universal Trial Number (UTN)
U1111-1150-9391
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic obstructive pulmonary disease 292213 0
Condition category
Condition code
Respiratory 292549 292549 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Exhaled nitric oxide will be measured in COPD patients following a course of oral steroid (prednisolone 30mg once daily for three weeks) and then, without 'wash-out' between courses, a course of high-dose inhaled corticosteroid (budesonide 800mcg twice daily for six weeks). The dose of inhaled budesonide will then be reduced to budesonide 400mcg twice daily for four weeks then budesonide 200mcg twice daily for four weeks then placebo inhaled for four weeks then stopped. Exhaled nitric oxide level will be monitored as the inhaled steroid dose is reduced. Participants will be blinded to whether they are taking oral or high-dose inhaled steroid in the first nine weeks of the study: oral liquid prednisolone vs. oral liquid placebo once daily, and budesonide dry powder inhaler twice daily vs. placebo dry powder inhaler twice daily. Participants will then be blinded to the dose of inhaled steroid during dose reduction for the remainder of the study (budesonide dry powder inhaler twice daily vs. placebo dry powder inhaler twice daily) Adherence to oral steroid will be monitored by drug return. Adherence to inhaled steroid will be monitored by Smartinhaler (Nexus6).
Intervention code [1] 289620 0
Treatment: Drugs
Comparator / control treatment
There is no direct comparator / control treatment. All patients will have exhaled nitric oxide measured after sequential courses of oral and inhaled corticosteroid as above.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 292437 0
Change in FENO level with reducing dose of oral then inhaled corticosteroid over 21 weeks. FENO level will be measured using a chemiluminescence nitric oxide analyser (GE Instruments).
Timepoint [1] 292437 0
21 weeks.
Secondary outcome [1] 308941 0
Relationship of FENO with serum markers of eosinophilic / T-helper 2 cell inflammation: peripheral eosinophils, IL-4, IL-5, IL-13 (measured by blood test / serum assay).
Timepoint [1] 308941 0
21 weeks.
Secondary outcome [2] 309355 0
Relationship of FENO with sputum markers of eosinophilic / T-helper 2 cell inflammation: sputum eosinophils, interleukins as above (measured by sputum induction / processing / assay).
Timepoint [2] 309355 0
21 weeks.
Secondary outcome [3] 309356 0
Relationship of FENO with forced expiratory volume in one second measured by spirometry.
Timepoint [3] 309356 0
21 weeks.
Secondary outcome [4] 309357 0
Relationship of FENO with six-minute walk test.
Timepoint [4] 309357 0
21 weeks.
Secondary outcome [5] 309358 0
Relationship of FENO with St Georges Respiratory Questionnaire.
Timepoint [5] 309358 0
21 weeks.

Eligibility
Key inclusion criteria
Diagnosis of COPD with post-bronchodilator FEV1 <80%.
Smoking history of >10 pack years.
Minimum age
45 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Bronchiectasis, lung cancer, diabetes.
Other co-morbidity likely to affect completion of the study.
Unable to undergo induced sputum test.
Current smokers.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Subjects will be enrolled from existing databases of COPD patients according to inclusion/exclusion criteria above. Subjects will enter a single group (i.e. no allocation concealment procedures necessary).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Single group
Other design features
Subjects will be blinded to the dose of corticosteroid they receive.
Phase
Phase 3 / Phase 4
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis
Participant number is based on previous studies demonstrating proportion of steroid-responders in COPD to be 20-25%. Results will be analysed using parametric and non-parametric tests.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
4/08/2014
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment outside Australia
Country [1] 6167 0
New Zealand
State/province [1] 6167 0
Otago

Funding & Sponsors
Funding source category [1] 289455 0
Charities/Societies/Foundations
Name [1] 289455 0
Healthcare Otago Charitable Trust
Country [1] 289455 0
New Zealand
Primary sponsor type
Individual
Name
Dr Jack Dummer
Address
Dr Jack Dummer
Otago Respiratory Research Unit
Department of Medicine
Dunedin School of Medicine
PO Box 56
Dunedin
9054
Country
New Zealand
Secondary sponsor category [1] 288142 0
None
Name [1] 288142 0
Address [1] 288142 0
Country [1] 288142 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291213 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 291213 0
Health and Disability Ethics Committees
1, The Terrace
C/- MEDSAFE, Level 6, Deloitte House
10 Brandon St
PO Box 5013
Wellington 6011
Ethics committee country [1] 291213 0
New Zealand
Date submitted for ethics approval [1] 291213 0
Approval date [1] 291213 0
20/03/2014
Ethics approval number [1] 291213 0
13/CEN/204

Summary
Brief summary
Firstly, we will examine the optimal way to determine personal-best exhaled nitric oxide levels in COPD patients. Our hypothesis is that lower exhaled nitric oxide levels can be achieved on oral compared with inhaled steroid. To test this, we will measure levels of exhaled nitric oxide in COPD patients on high-dose inhaled and oral steroid.
Secondly, we will examine the effect of inhaled steroid dose on exhaled nitric oxide levels and markers of TH2/eosinophilic airway inflammation in COPD. Our hypothesis is that, as inhaled steroid dose is decreased, any increase in FENO from baseline will be associated with a change in other markers of TH2/eosinophilic airway inflammation. To test this, we will measure exhaled nitric oxide levels and take measures of blood and sputum markers of TH2/eosinophilic airway inflammation in COPD patients on a step-wise reducing course from high-dose to low-dose inhaled steroid and then to placebo.
Thirdly, we will examine measures of health status (lung function, quality of life and functional status) in patients with COPD. Our hypothesis is that any decrease in health status on a reducing course of inhaled steroid is associated with an increase in exhaled nitric oxide level. To test this, we will measure exhaled nitric oxide levels and take measures of health status in COPD patients on a step-wise reducing course from high-dose to low-dose inhaled steroid and then to placebo.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49306 0
Dr Jack Dummer
Address 49306 0
Otago Respiratory Research Unit
Department of Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin
9054
Country 49306 0
New Zealand
Phone 49306 0
+64 3 4740999 ext. 8785
Fax 49306 0
Email 49306 0
[email protected]
Contact person for public queries
Name 49307 0
Ms Jan Cowan
Address 49307 0
Otago Respiratory Research Unit
Department of Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin
9054
Country 49307 0
New Zealand
Phone 49307 0
+64 3 4740999 ext. 8785
Fax 49307 0
Email 49307 0
[email protected]
Contact person for scientific queries
Name 49308 0
Dr Jack Dummer
Address 49308 0
Otago Respiratory Research Unit
Department of Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin
9054
Country 49308 0
New Zealand
Phone 49308 0
+64 3 4740999 ext. 8785
Fax 49308 0
Email 49308 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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