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Trial registered on ANZCTR


Registration number
ACTRN12612000206820
Ethics application status
Approved
Date submitted
5/02/2012
Date registered
20/02/2012
Date last updated
27/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
ROBUST- Reduction Of exacerbations in Bronchiectasis USing Tiotropium
Scientific title
A multi-centre, double-blind, randomised, placebo-controlled crossover study of tiotropium treatment in adult patients with stable, non-cystic fibrosis bronchiectasis
Secondary ID [1] 279876 0
None
Universal Trial Number (UTN)
Trial acronym
ROBUST- Reduction Of exacerbations in Bronchiectasis USing Tiotropium
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-cystic Bronchiectasis 285782 0
Condition category
Condition code
Respiratory 285958 285958 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Inhaled Tiotropium or placebo 18 microgram daily for 6 months with a washout period of 4 weeks then crossover to the opposite arm of treatment for another 6 months.
Intervention code [1] 284200 0
Treatment: Drugs
Comparator / control treatment
Placebo will be manufactured identical to tiotropium but without the active ingredients.
Control group
Placebo

Outcomes
Primary outcome [1] 286444 0
Event-based exacerbation frequency- ascertained using data from the daily diary card kept by participants and clinical assessment during follow up visits.
Timepoint [1] 286444 0
week 0-26 ; week 30 to 54
Secondary outcome [1] 295902 0
Symptom-based exacerbation frequency - ascertained using data from the daily diary card kept by participants and clinical assessment during follow up visits.
Timepoint [1] 295902 0
week 0-26 ; week 30 to 54
Secondary outcome [2] 295903 0
Time to first exacerbation - ascertained using data from the daily diary card kept by participants and clinical assessment during follow up visits.
Timepoint [2] 295903 0
week 0-26 ; week 30 to 54
Secondary outcome [3] 295904 0
Health-related quality of life measured by changes in health questionnaires
Timepoint [3] 295904 0
At week "0", "26", "30" and "56"
Secondary outcome [4] 295905 0
Change in Forced vital capacity (FVC) - measured by performing forced spirometry at protocol required follow up visits.
Timepoint [4] 295905 0
At screening, week"0", "4", "13", "26", "30", "34", "43" and "56"
Secondary outcome [5] 295906 0
Change in Exercise capacity measured by 6 minutes walk test
Timepoint [5] 295906 0
At screening, week "0", "26", "30" and "56"
Secondary outcome [6] 295907 0
Change in markers of airway inflammation - by comparing sputum analysis results on sputum samples collected at baseline and end of treatment for each treatment period.
Timepoint [6] 295907 0
At screening, week"26", "30" and "56"
Secondary outcome [7] 295908 0
Cost and cost effectiveness of tiotropium treatment - cost analysis from participants daily diary card recording visits to General Practitioners or other Health providers.
Timepoint [7] 295908 0
At week"0", "4", "13", "26", "30", "34", "43" and "56"
Secondary outcome [8] 295909 0
Adverse events such as dry mouth, dry skin, blurred vision and difficulty in passing urine will be assessed at every follow up clinic visits.
Timepoint [8] 295909 0
At week"0", "4", "13", "26", "30", "34", "43" and "56"
Secondary outcome [9] 296022 0
Airway function measured by FEV1 changes
Timepoint [9] 296022 0
At screening, week"0", "4", "13", "26", "30", "34", "43" and "56"

Eligibility
Key inclusion criteria
- adult patients
- able to provide written informed consent
- confirmed diagnosis of bronchiectasis by high resolution CT scan
- FEV1/FVC ratio < 70%
- History of at least one pulmonary exacerbation requiring antibiotic treatment in the past 12 months
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Smoking history of > 20 pack years

Primary diagnosis of asthma defined as 1 or more admissions to hospital in the past year with a primary discharge diagnosis of asthma or a history of more courses of oral steroids than antibiotics in the past year

Continuous antibiotic therapy

Known adverse reaction to tiotropium

Cystic fibrosis

Hypogammaglobulinaemia

Allergic BronchoPulmonary Aspergillosis

History of non-tuberculous mycobacterial infection (treated or untreated)

Bronchiectasis exacerbation or respiratory infection requiring oral or intravenous antibiotic within 6 weeks before randomisation

Use of oral corticosteroid medication at unstable doses (i.e. less than six weeks on a stable dose) or at doses more than or equal to 10 mg/day

Unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year

Any other serious co-existing illness that precludes patients from the study

Narrow-angle glaucoma

Symptomatic prostatic hyperplasia or bladder-neck obstruction (patients whose symptoms are controlled on treatment may be included)

Inability to complete HRQL questionnaires

Female patients who are pregnant or breast feeding

Known non-compliance with medications and follow ups

Patients taking tiotropium (can be included if they are willing to withhold tiotropium for two weeks prior to randomisation and throughout the whole duration of the study)

Patients who are unable or unwilling to stop ipratropium (Atrovent inhaler). A salbutamol inhaler may be substituted for the ipratropium inhaler

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 is concealed, all study personnel and participants are "blinded" and randomisation is sequential using the number on the study drug packs.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be stratified by centres (there are a total of 3 centres) with an equal allocation of patients within centre to each group using random permuted blocks. The computer-generated randomisation numbers will generate a drug kit code that is to be assigned as subject numbers at each site.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
NA
Phase
Not Applicable
Type of endpoint(s)
Efficacy
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 outside Australia
Country [1] 4107 0
New Zealand
State/province [1] 4107 0
Auckland
Country [2] 4108 0
New Zealand
State/province [2] 4108 0
Hamilton

Funding & Sponsors
Funding source category [1] 284649 0
Government body
Name [1] 284649 0
Health Research Council
Address [1] 284649 0
Level 3 - ProCARE Building, 110 Stanley Street (access via Grafton Mews), Auckland 1010
Country [1] 284649 0
New Zealand
Primary sponsor type
Government body
Name
Health Research Council
Address
Level 3 - ProCARE Building, 110 Stanley Street (access via Grafton Mews), Auckland 1010
Country
New Zealand
Secondary sponsor category [1] 283557 0
None
Name [1] 283557 0
NA
Address [1] 283557 0
NA
Country [1] 283557 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286642 0
Northern Y Regional Ethics Committee
Ethics committee address [1] 286642 0
c/- Ministry of Health
PO Box 1031
Hamilton 3240
New Zealand
Ethics committee country [1] 286642 0
New Zealand
Date submitted for ethics approval [1] 286642 0
10/10/2011
Approval date [1] 286642 0
19/12/2011
Ethics approval number [1] 286642 0
NTY/11/10/104

Summary
Brief summary
The study aims to assess the effect of tiotropium compared with placebo in adult patients with non-cystic bronchiectasis with airflow obstruction.

The primary aim is to assess whether tiotropium reduces event-based exacerbation frequency.

And the secondary aims are whether tiotropium increases time to first exacerbation, improves lung function,
reduces symptom-based exacerbation, improves quality of life, reduces airway inflammation, reduces bacterial infection and improves exercise capacity and forced vital capacity.
Trial website
NA
Trial related presentations / publications
NA
Public notes

Contacts
Principal investigator
Name 33736 0
Dr Conroy Wong
Address 33736 0
C/- Respiratory department
Middlemore Hospital
100 Hospital Rd
Papatoetoe
Auckland 2015
Country 33736 0
New Zealand
Phone 33736 0
+ 64 9 2760000
Fax 33736 0
Email 33736 0
cawong@middlemore.co.nz
Contact person for public queries
Name 16983 0
Dr Dr Conroy Wong
Address 16983 0
Respiratory Services, Middlemore Hospital
Hospital Road, Otahuhu
Auckland 1640
Country 16983 0
New Zealand
Phone 16983 0
0064 9 276 0000
Fax 16983 0
0064 9 2709737
Email 16983 0
cawong@middlemore.co.nz
Contact person for scientific queries
Name 7911 0
Dr Dr Conroy Wong
Address 7911 0
Respiratory Services, Middlemore Hospital
Hospital Road, Otahuhu
Auckland 1640
Country 7911 0
New Zealand
Phone 7911 0
0064 9 276 0000
Fax 7911 0
0064 9 2709737
Email 7911 0
cawong@middlemore.co.nz

No data has been provided for results reporting
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