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Trial registered on ANZCTR


Registration number
ACTRN12613000214730
Ethics application status
Not yet submitted
Date submitted
20/02/2013
Date registered
22/02/2013
Date last updated
22/08/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised trial of therapeutic ultrasound for chronic rhinosinusitis in adults with cystic fibrosis
Scientific title
In adults with cystic fibrosis, what is the effect of therapeutic ultrasound versus sham ultrasound on rhinosinusitis-specific and general quality of life, nasal patency, lung function, perceived global change and medication use.
Secondary ID [1] 281993 0
Nil known
Universal Trial Number (UTN)
U1111-1139-6737
Trial acronym
TUSC Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cystic fibrosis 288429 0
chronic rhinosinusitis 288430 0
Condition category
Condition code
Respiratory 288779 288779 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Therapeutic ultrasound. Participants will receive ultrasound insonation over each mixillary sinus for 5 minutes at 1 MHz and 1 W/cm^2, and over each frontal sinus for 4 minutes at 1 MHz and 0.5 W/cm^2. This 18-minute treatment will be applied 6 times during a 2-week period.
Intervention code [1] 286565 0
Treatment: Devices
Comparator / control treatment
Sham ultrasound. Participants will undergo the same regimen as described for the intervention group except the ultrasound machine will be deactivated so that it does not supply any ultrasound.
Control group
Placebo

Outcomes
Primary outcome [1] 288915 0
Rhinosinusitis-specific quality of life, measured by the 22-item Sino-Nasal Outcomes Test (SNOT-22).
Timepoint [1] 288915 0
The primary timepoint will be at the end of the 2-week treatment period. This outcome will also be measured at other times as a secondary outcome (see below).
Secondary outcome [1] 301323 0
Rhinosinusitis-specific quality of life, measured by the 22-item Sino-Nasal Outcomes Test (SNOT-22).
Timepoint [1] 301323 0
Week 0 (baseline), 1, 4, and 8
Secondary outcome [2] 301324 0
Nasal patency, assessed using peak nasal inspiratory flow (via a peak flow meter with a face mask and the mouth closed).
Timepoint [2] 301324 0
Weeks 0 (baseline), 1, 2, 8
Secondary outcome [3] 301325 0
Lung function will be measured via spirometry according to ATS/ERS criteria.
Timepoint [3] 301325 0
Weeks 0 (baseline), 1, 2, 8
Secondary outcome [4] 301326 0
Global rating of change will be participant reported on a 15-point scale from -7 ‘a very great deal worse’ to +7 ‘a very great deal better’.
Timepoint [4] 301326 0
Weeks 1, 2, 4, 8
Secondary outcome [5] 301327 0
General health-related quality of life will be assessed with the Short Form 36 (SF36). Individual domains and physical and mental summaries will be calculated.
Timepoint [5] 301327 0
Weeks 0 (baseline), 1, 2, 4, 8
Secondary outcome [6] 301328 0
Medication use will be reported by the participant at each visit. The investigator conducting the visit will enter all current medications on the case report form at Week 0. At subsequent visits, the investigator will enter the start date of any new medications and the end date of any ceasing medications.
Timepoint [6] 301328 0
Weeks 0 (baseline), 1, 2, 4, 8
Secondary outcome [7] 301329 0
Adverse events that occur between visits will be reported by the participant at each visit. Participants will also be advised to report any adverse events that occur during the treatment. The investigator conducting the visit will record the start day/time, duration and description of any adverse events. All adverse changes in health condition from baseline will be recorded. Adverse events may include those that are common in CF (e.g., increased cough, increased sputum), those that common in adults generally (e.g., sprained ankle, headache), and those that are known can occur with therapeutic ultrasound (e.g., increased local heating).
Timepoint [7] 301329 0
Weeks 1, 2, 4, 8

Eligibility
Key inclusion criteria
To participate in this study, a person must: be 18 years of age or older; have cystic fibrosis confirmed by genetic testing; be clinically stable, defined as a forced expiratory volume in one second (FEV1) within 10% of his/her best outpatient value in the past 6 months; be able to read, write and comprehend English; be able and willing to attend the outpatient department for all scheduled visits; have had at least 2 rhinosinusitis symptoms for at least the past 3 months; and have at least one objective sign of rhinosinusitis at the time of enrolment. The symptoms and signs are those defined by the European consensus statements (Fokkens 2007, 2012). The symptoms must include at least one of either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), with facial pain/pressure or reduction/loss of smell. The sign can be polyps, mucopurulent discharge primarily from middle meatus, or oedema/mucosal obstruction in middle meatus seen with simple anterior rhinoscopy, or changes in the ostiomeatal complex on CT, if available.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
A person will be ineligible to participate in this study if s/he: has significant malignant, neurological or musculoskeletal conditions; is unable to perform spirometry reproducibly; has hot-cold insensitivity over the sinuses; has had a lung transplant; has had polypectomy or sinus surgery in the past year; has had therapeutic ultrasound to the sinuses in the past 3 months, or has had non-routine antibiotics in the past 2 weeks. Non-routine antibiotics are defined as those taken for less than 3 months.

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)
All patients enrolled at the Cystic Fibrosis Clinic at Royal Prince Alfred Hospital, Sydney, are adults and undergo genetic confirmation of cystic fibrosis when they join the clinic. Therefore, all patients will be screened by one of the named investigators for eligibility regarding symptoms in clinic or by telephone. Patients with at least 2 rhinosinusitis symptoms for at least the past 3 months will be invited to read an Information for Participants document and attend a baseline visit.
At the baseline visit, patients will undergo spirometry, simple anterior rhinoscopy, and a hot-cold sensitivity test to complete confirmation of eligibility. Patients who are eligible and consent to participate will undergo the remaining baseline measures (height, weight, 22-item Sino-Nasal Outcome Test, Short Form 36, medication use, past treatment for sinusitis, and peak nasal inspiratory flow) and then will be randomised to ultrasound or sham ultrasound so that their first dose of the intervention can be commenced at the same visit.
A random allocation schedule will be sealed in opaque envelopes by an independent investigator. After confirmation of eligibility, the next available ID number will be given to the new participant and they will be allocated to machine A or machine B according to the contents of the envelope linked to that ID number.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer-generated random allocation schedule (in blocks containing an equal proportion of allocations to A and B, with randomly varying block sizes) will be prepared.
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
intention-to-treat analysis
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
To detect the minimum clinically important difference in SNOT-22 score of 9 points between groups with 80% power, alpha of 0.05, and a SD of 11 (based on pilot data in 23 RPA patients meeting the eligibility criteria), we calculated we would need a total of 25 participants per group. A total of 56 participants will allow for 10% loss to follow-up. Continuous outcomes will be analysed as mean between-group differences with 95% CIs, or using the Mann-Whitney U test if data are not normally distributed. Adverse events will be analysed as relative risks. All analyses will follow intention to treat.

Recruitment
Recruitment status
Not yet recruiting
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)
NSW
Recruitment hospital [1] 634 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 6367 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 5329 0
United Kingdom
State/province [1] 5329 0
Dorset

Funding & Sponsors
Funding source category [1] 286773 0
Charities/Societies/Foundations
Name [1] 286773 0
Physiotherapy Research Foundation
Address [1] 286773 0
1175 Toorak Road, Camberwell, VIC 3124

Country [1] 286773 0
Australia
Primary sponsor type
Hospital
Name
Royal Prince Alfred Hospital, Sydney Local Health District
Address
Missenden Rd, Camperdown, NSW 2050
Country
Australia
Secondary sponsor category [1] 285556 0
Hospital
Name [1] 285556 0
Poole Hospital NHS Foundation Trust
Address [1] 285556 0
Longfleet Road, Poole, Dorset BH15 2JB
Country [1] 285556 0
United Kingdom

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 288838 0
Sydney Local Health District Ethics Review Committee - RPAH Zone
Ethics committee address [1] 288838 0
Research Development Office
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Ethics committee country [1] 288838 0
Australia
Date submitted for ethics approval [1] 288838 0
23/01/2013
Approval date [1] 288838 0
Ethics approval number [1] 288838 0
X13-0026

Summary
Brief summary
Research question: Does therapeutic ultrasound reduce the severity of rhinosinusitis in adults with cystic fibrosis (CF)?

Methods: Adults with CF and chronic rhinosinusitis will be randomly allocated to receive ultrasound or sham ultrasound in a hospital outpatient clinic, 6 times in 2 weeks. The primary outcome will be the severity of rhinosinusitis symptoms, measured using the 22-item Sino-Nasal Outcome Test after the treatment period. Secondary outcome measures will be peak nasal inspiratory flow, lung function, global rating of change, a generic health-related quality of life questionnaire, medication use, and adverse events. Measurements will occur during and 6 weeks beyond treatment.

Significance: This study will determine whether therapeutic ultrasound reduces rhinosinusitis symptoms in adults with CF to a clinically worthwhile extent and whether any effect extends beyond the treatment period. Growing evidence indicates that sinusitis seeds the lower respiratory tract with infection, so an effective rhinosinusitis treatment may also have respiratory benefits, which are crucial for people with CF. Ultrasound use has decreased since it was shown to be ineffective for many conditions. If the study shows ultrasound is effective for CF rhinosinusitis, physiotherapists’ apply their skills and this equipment to treat CF rhinosinusitis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 38014 0
Prof Peter Bye
Address 38014 0
Dept of Resp Med
RPA Hospital
Missenden Rd
Camperdown NSW 2050
Country 38014 0
Australia
Phone 38014 0
+61 2 9515 7427
Fax 38014 0
+61 2 9515 8196
Email 38014 0
peter.bye@sydney.edu.au
Contact person for public queries
Name 38015 0
Dr Mark Elkins
Address 38015 0
Dept of Resp Med
RPA Hospital
Missenden Rd
Camperdown NSW 2050
Country 38015 0
Australia
Phone 38015 0
+61 4 6637 8837
Fax 38015 0
+61 2 9515 8196
Email 38015 0
mark.elkins@sydney.edu.au
Contact person for scientific queries
Name 38016 0
Dr Mark Elkins
Address 38016 0
Dept of Resp Med
RPA Hospital
Missenden Rd
Camperdown NSW 2050
Country 38016 0
Australia
Phone 38016 0
+61 4 6637 8837
Fax 38016 0
+61 2 9515 8196
Email 38016 0
mark.elkins@sydney.edu.au

No information has been provided regarding IPD availability
Summary results
No Results