Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001344583
Ethics application status
Approved
Date submitted
27/11/2015
Date registered
9/12/2015
Date last updated
17/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Anti-inflammatory effects of oral and transdermal clonidine in bronchiectasis
Scientific title
The effect of clonidine on sputum cytokines in patients with bronchiectasis
Secondary ID [1] 287975 0
Nil Known
Universal Trial Number (UTN)
U111111750390
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bronchiectasis 296854 0
Condition category
Condition code
Respiratory 297087 297087 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Name:Anti-inflammatory effects of oral and transdermal clonidine in bronchiectasis.
Dose:150micrograms oral clonidine twice a day or 300micrograms transdermal clonidine once a week.
Study Duration: 8 weeks
Mode of administration: Oral tablet or transdermal patch
Adherance measured by recording returned pill and patch counts at each visit.
Intervention code [1] 293318 0
Treatment: Drugs
Comparator / control treatment
150micrograms oral clonidine taken twice a day will be compared with a 300micrograms transdermal clonidine patch replaced once a week.
Neither of these treatments are standard of care or the control.
Control group
Active

Outcomes
Primary outcome [1] 296691 0
Change in concentration of sputum IL-8
Timepoint [1] 296691 0
Baseline and 8 weeks
Secondary outcome [1] 319132 0
Change in markers of airway inflammation
(sputum neutrophils, sputum cytokines - GM-CSF, IFN-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-alpha)
Timepoint [1] 319132 0
Baseline and 8 weeks
Secondary outcome [2] 319218 0
Change in markers of systemic inflammation
(Serum CRP and cytokines, blood neutrophils).
Timepoint [2] 319218 0
Baseline and 8 weeks
Secondary outcome [3] 319219 0
Frequency of adverse events (The most commonly reported side effects of clonidine include drowsiness, dry mouth, fatigue, nausea, constipation, headache, dizziness, insomnia, hypotension, and bradycardia. These side effects commonly subside or decrease variably over time and are thought to be dose dependent. Local skin reactions are common but usually mild with transdermal clonidine)which will be assessed by:
- self reporting
- diary cards
Timepoint [3] 319219 0
4 weeks and 8 weeks
Secondary outcome [4] 319220 0
Change in lung function (FEV1,FVC) assessed by spirometry.
Timepoint [4] 319220 0
Screening, Baseline, 4 weeks and 8 weeks
Secondary outcome [5] 319222 0
Health-related quality of life
(QOL-B, SGRQ)
Timepoint [5] 319222 0
Baseline and 8 weeks

Eligibility
Key inclusion criteria
1.Aged greater than or equal to 18 and less than or equal to 90 years
2.Able to provide written informed consent
3.Able to provide spontaneous sputum sample at visit 2 (week 0).
4.High resolution CT scan (HRCT) diagnosis of bronchiectasis; CT scan performed within the past 5 years
5.Clinically stable during baseline period, which is 4 weeks prior to randomisation; (as defined by the absence of clinical worsening beyond normal daily variation, with no need for increasing habitual medications or taking antibiotics or prednisone and stable spirometry)
6.History of at least one pulmonary exacerbation requiring antibiotic treatment in the past 12 months.
Patients with asthma and COPD will be included if the primary diagnosis is bronchiectasis.
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Patients with significant abnormal liver function (AST/ALT greater than 2x upper limit of normal range) or liver cirrhosis (15-30% clonidine is metabolised in the liver)
2.Known history of allergy or reaction to clonidine
3.Systolic blood pressure less than 100 mmHg
4.Bradyarrhythmia due to 2nd or 3rd degree AV block or sick sinus syndrome.
5.Active dermatitis preventing application of a clonidine patch on upper outer arm or chest.
6.Continuous antibiotic therapy (greater than 3 months)
7.Long term macrolide treatment (greater than or equal to 3 months) in the past 6 months
Patients taking continuous oral corticosteroids (greater than 6 weeks) or immunosuppressive agents (e.g. azathioprine, methotrexate, cyclophosphamide).
8.Bronchiectasis exacerbation or respiratory infection requiring oral or intravenous antibiotic or steroid treatment within 4 weeks prior to commencing study drug.
9.Patients with a history of nonadherence with medications

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)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated random number list
Patients will be randomly assigned in a 1:1 ratio, with a permuted block randomisation, stratified by centre.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Multi-centre, parallel, pre-post, open-label study
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
We base our sample size of 40 participants on the baseline values from two randomised studies of good quality whose participants were broadly similar to ROBUST’s, except in regard to ethnicity. The pooled baseline geometric mean and coefficient of variation of sputum IL-8 in these studies were 15,300 pg/ml and 1.58 respectively. The correlation between baseline and 4-week IL-8 log-concentrations implied by Stockley’s results exceeded 0.9 in both arms. We expect this correlation to be about 0.8 at 8 weeks. Clustering by site yields an ICC estimated at 0.12 (the observed ICC for FEV1% in the ROBUST study). The maximum expected attrition is 5%, observed over 12 months for the EMBRACE study. From these three considerations, the power from the planned 40 participants is effectively that of 40x2.8/2.4x0.95 greater than or equal to 43 participants, and is sufficient to detect a relative reduction of 46% in sputum IL-8 with 80% power. This can be compared to a relative reduction of approximately 55% in IL-8 afforded by erythromycin and of 66% afforded by a 4-week treatment with fluticasone.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/12/2015
Actual
22/02/2016
Date of last participant enrolment
Anticipated
5/12/2016
Actual
16/10/2017
Date of last data collection
Anticipated
Actual
22/02/2018
Sample size
Target
40
Accrual to date
Final
37
Recruitment outside Australia
Country [1] 7358 0
New Zealand
State/province [1] 7358 0
Auckland, Hamilton

Funding & Sponsors
Funding source category [1] 292442 0
Government body
Name [1] 292442 0
Health Research Council
Country [1] 292442 0
New Zealand
Primary sponsor type
Individual
Name
Dr Conroy Wong
Address
Respiratory Department
Middlemore Hospital
100 Hospital Road
Papatoetoe
Auckland 2025
Country
New Zealand
Secondary sponsor category [1] 291135 0
None
Name [1] 291135 0
Address [1] 291135 0
Country [1] 291135 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293904 0
Southern Health and Disabiltiy Ethics Committee
Ethics committee address [1] 293904 0
Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 293904 0
New Zealand
Date submitted for ethics approval [1] 293904 0
01/10/2015
Approval date [1] 293904 0
02/11/2015
Ethics approval number [1] 293904 0
15/STH/178

Summary
Brief summary
Bronchiectasis is a troublesome disease characterised by productive cough, airway inflammation, and repeated bacterial infections requiring antibiotics. The main aim of this study is to assess whether Clonidine can reduce inflammation in the lungs. We will also assess whether similar effects are seen in the bloodstream. We are
interested to see if (transdermal) skin patches of Clonidine are better than oral tablets in controlling inflammation, and which treatment is better tolerated. This study will provide important information for the development of a larger study to assess whether Clonidine treatment can prevent symptom flareups(exacerbations) in patients with bronchiectasis.
Participants will attend 4 study visits over the 8 week study where they will have their health assessed (vital signs,lung function, sputum and blood samples taken), complete questionnaires and study diaries.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61766 0
Dr Conroy Wong
Address 61766 0
Respiratory Department
Middlemore Hospital
100 Hospital Rd
Papatoetoe
Auckland 2025
Country 61766 0
New Zealand
Phone 61766 0
+ 64 21 613307
Fax 61766 0
Email 61766 0
cawong@middlemore.co.nz
Contact person for public queries
Name 61767 0
Dr Conroy Wong
Address 61767 0
Respiratory Department
Middlemore Hospital
100 Hospital Rd
Papatoetoe
Auckland 2025
Country 61767 0
New Zealand
Phone 61767 0
+ 64 21 613307
Fax 61767 0
Email 61767 0
cawong@middlemore.co.nz
Contact person for scientific queries
Name 61768 0
Dr Conroy Wong
Address 61768 0
Respiratory Department
Middlemore Hospital
100 Hospital Rd
Papatoetoe
Auckland 2025
Country 61768 0
New Zealand
Phone 61768 0
+ 64 21 613307
Fax 61768 0
Email 61768 0
cawong@middlemore.co.nz

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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