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Trial registered on ANZCTR


Registration number
ACTRN12619001398190
Ethics application status
Approved
Date submitted
25/09/2019
Date registered
14/10/2019
Date last updated
14/10/2019
Date data sharing statement initially provided
14/10/2019
Date results information initially provided
14/10/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effects of topical and oral corticosteroids on sinonasal microbiome
Scientific title
The clinical and microbiome outcomes of medical treatments in chronic rhinosinusitis: a double-blinded, randomised placebo-controlled trial
Secondary ID [1] 299402 0
TGA: CT-2016-CTN-01960-1 v1
Universal Trial Number (UTN)
U1111-1240-9725
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic rhinosinusitis 314579 0
Condition category
Condition code
Infection 312919 312919 0 0
Other infectious diseases
Inflammatory and Immune System 312920 312920 0 0
Other inflammatory or immune system disorders
Respiratory 313005 313005 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A randomised double-blinded placebo-controlled trial in patients with chronic rhinosinusitis.

Group 1 receives oral unlabelled Panafcortelone (Prednisolone, Aspen Pharmacare, St Leonards, NSW), in a tapering dose (25mg/day for 1 week then 12.5mg/day for 1 week then 12.5 mg every other day for 1 week) + 200ml isotonic saline with water for injection (2ml respules) as placebo delivered intranasally 2 times a day + oral placebo for antibiotic 2 tablets on day one, followed by one tablet once daily for 3 weeks

Group 2 receives topical steroid Pulmicort ® (Budesonide, 0.5mg/2ml respules) washes of the nasal cavities and sinuses delivered intranasally 2 times a day in 200 ml isotonic saline + oral placebo for antibiotic 2 tablets on day one, followed by one tablet once daily + placebo for oral steroid as mentioned above in tapering doses for three weeks

Group 3 receives oral antibiotic, Doxylin® (Doxycycline, antibiotic) tablets 2 tablets on day one (200mg), followed by one tablet (100mg) once daily + placebo for steroid in tapering doses as mentioned above + 200ml isotonic saline with water for injection (2ml respules) as placebo delivered intranasally 2 times a day for 3 weeks.

The placebo oral medication is prepared by Professional Pharmaceutical Packaging Pty, Ltd (VIC, Australia) and the placebo for Pulmicort respules was 2mL water for injections (Pfizer, Brooklyn, USA).

The patients are asked to maintain a diary for the daily documentation of treatment taken and also asked to bring back the medicine bottles and the used vials back to the pharmacy.
The three sets of treatments (one active and two placebo) are taken simultaneously by the patients. For example, in the group 1, the day 1 of the oral placebo for oral antibiotic is day 1 of week 1 for the panafcortelone.
The Placebos consists of gelatin capsules and microcrystalline cellulose USP/NF United States Pharmacopeia (USP) and the National Formulary (NF)
Both placebos are prepared by level filling the preformed gelatin capsules. This is estimated at 300mg per capsule.
Intervention code [1] 315655 0
Treatment: Drugs
Intervention code [2] 315704 0
Treatment: Other
Comparator / control treatment
At the commencement of the study all patients received identical appearing treatment packs, consisting of unlabelled oral medication, FLO sinus care irrigation sachets (ENT technologies, Melbourne, Australia and an irrigation bottle and vials containing a solution that were to be added to the FLO irrigation solution at each sinus lavage. Only one of the treatments in the pack had an active medical ingredient, the remaining treatments were placebo.
Each arm has an active agent and placebo representing the other two treatments and hence act as a comparator in itself to look into intra treatment effects. Also, the third group which received antibiotic will be compared against the steroid arms (group 1 and 2). Doxycycline will be given as 200mg once daily dose on day 1 followed by 100mg once daily for a total 3-week duration of treatment.
Control group
Active

Outcomes
Primary outcome [1] 321518 0
changes in patient clinical scores as seen by the Sinonasal outcome test-22 using a patient directed questionnaire.
Timepoint [1] 321518 0
Baseline at the time of recruitment
3 weeks post intervention (primary timepoint )
6 weeks post intervention
Primary outcome [2] 321519 0
Change in sinonasal microbiome profile.
This will be assessed by taking endoscopic guided nasal microbiome swabs from the middle meatus of the patients. The swabs wills be stored at -80 freezer for extraction of bacterial DNA at the completion of patient recruitment. This would be further analysed to obtain the microbiome profile in the sinuses of the CRS patients.
Timepoint [2] 321519 0
Baseline at the time of recruitment
3 weeks post intervention (primary timepoint )
6 weeks post intervention
Primary outcome [3] 321569 0
changes in patient clinical scores as seen by Lund Kennedy score.
This is a nasal endoscopic score which will be done during the endoscopic examination of the patients. This is used to assess the disease severity by scoring the oedema, polyps and discharge.
Timepoint [3] 321569 0
Baseline at the time of recruitment
3 weeks post intervention (primary timepoint )
6 weeks post intervention
Secondary outcome [1] 375209 0
changes in patient clinical scores as seen by Adelaide sinus symptom score using a patient directed questionnaire.
Timepoint [1] 375209 0
Baseline at the time of recruitment
3 weeks post intervention
6 weeks post intervention

Eligibility
Key inclusion criteria
Selection/inclusion criteria:
Patients who meet ALL of the following criteria will be offered inclusion in the study:
(1) Have symptoms and signs of CRS and require medical management AND
(2) are over 18 years of age AND
(3) are able to give written informed consent AND
(4) are local patients who will be returning to this centre for follow-up care

Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Exclusion criteria:
(1) Requirement for a specific corticosteroid or antibiotic treatment based on symptomatology
(2) allergy to steroids
(3) pregnant or breastfeeding
(4) diabetes
(5) on other CYP450 inhibiting drugs (e.g. ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir and telithromycin)
(6) liver disease

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)
Permuted block randomisation
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
QIIME 2 (version 2018.11) will be used for bioinformatics pipeline. Outcome measures will be analysed using a repeated measures ANOVA model without the treatment variable but with the interaction between treatment and time specified as a covariate.

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 in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 14853 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 28119 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 303908 0
Charities/Societies/Foundations
Name [1] 303908 0
The Garnett Passe and Rodney Williams memorial foundation conjoint grant
Address [1] 303908 0
Suite 2/06, 517 Flinders Ln, Melbourne VIC 3000, Australia
Country [1] 303908 0
Australia
Primary sponsor type
Individual
Name
Associate Professor Psaltis
Address
Department of Otolaryngology, Head and Neck Surgery
The Queen Elizabeth Hospital
Tower Block 3C, 28 Woodville Road
Woodville South SA 5011
Country
Australia
Secondary sponsor category [1] 304056 0
University
Name [1] 304056 0
University of Adelaide
Address [1] 304056 0
Adelaide SA 5005, Australia
Country [1] 304056 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304414 0
The Queen Elizabeth Hospital Human Research Ethics Committee (TQEH/LMH/MH)
Ethics committee address [1] 304414 0
The Queen Elizabeth Hospital Basil Hetzel Institute DX465101 28 Woodville Road Woodville South SA 5011
Ethics committee country [1] 304414 0
Australia
Date submitted for ethics approval [1] 304414 0
03/11/2015
Approval date [1] 304414 0
18/04/2016
Ethics approval number [1] 304414 0
HREC/15/TQEH/177

Summary
Brief summary
The purpose of this study to enhance our understanding of the interactions between medications and the bacterial populations (which together comprise the microbiome) in the nose and sinuses. Our hypothesis is that both oral and topical steroids will differentially alter bacterial profiles in patients with CRS to influencing the clinical outcomes in patients.

We will target patients in the pre-operative clinic presenting with symptoms consistent with a diagnosis of CRS. Patients who require medical management of their symptoms and consent to participate will be randomised to one of three groups, each of which consists of one of the standard treatment regimens for the pre-operative medical management of CRS (oral steroid or topical steroid or oral antibiotic).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96870 0
A/Prof Alkis Psaltis
Address 96870 0
Department of Otolaryngology, Head and Neck Surgery
The Queen Elizabeth Hospital
Tower Block 3C
28 Woodville Road
Woodville South SA 5011
Country 96870 0
Australia
Phone 96870 0
+61 8 8222 6782
Fax 96870 0
Email 96870 0
alkis.psaltis@adelaide.edu.au
Contact person for public queries
Name 96871 0
Dr Lisa Mary Cherian
Address 96871 0
Department of Otolaryngology, Head and Neck Surgery
The Queen Elizabeth Hospital
Tower Block 3C
28 Woodville Road
Woodville South SA 5011
Country 96871 0
Australia
Phone 96871 0
+61882227158
Fax 96871 0
Email 96871 0
lisa.cherian@adelaide.edu.au
Contact person for scientific queries
Name 96872 0
Dr Lisa Mary Cherian
Address 96872 0
Department of Otolaryngology, Head and Neck Surgery
The Queen Elizabeth Hospital
Tower Block 3C
28 Woodville Road
Woodville South SA 5011
Country 96872 0
Australia
Phone 96872 0
+6182227158
Fax 96872 0
Email 96872 0
lisa.cherian@adelaide.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De- identified IPD underlying published results only
When will data be available (start and end dates)?
Beginning 3 months and ending 5 years following main results publication
Available to whom?
Case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
IPD meta- analyses
How or where can data be obtained?
Access subject to approvals by Principle Investigator (alkis.psaltis@adelaide.edu.au)
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary