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Trial registered on ANZCTR


Registration number
ACTRN12621000688886
Ethics application status
Approved
Date submitted
19/04/2021
Date registered
7/06/2021
Date last updated
10/05/2022
Date data sharing statement initially provided
7/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating the additional effect of clarithromycin in the standard of care for non-eosinophilic Chronic Rhinosinusitis patients
Scientific title
A double-blinded randomised control trial evaluating the efficacy of additional long-term low-dose Clarithromycin versus standard of care on post-operative symptomatic outcomes in the treatment of non-eosinophilic Chronic Rhinosinusitis in adults
Secondary ID [1] 304001 0
None
Universal Trial Number (UTN)
None
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic rhinosinusitis 321616 0
Condition category
Condition code
Surgery 319360 319360 0 0
Other surgery
Inflammatory and Immune System 319823 319823 0 0
Other inflammatory or immune system disorders
Infection 319895 319895 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention will be a Long-Term Low-Dose Clarithromycin administration post endoscopic surgery. If participants meet all inclusion criteria, the intervention will commence 6 weeks post surgery.

- the dose: 250mg once daily.
- the duration of administration: 3 months.
- the mode of administration: oral tablet.
Intervention code [1] 320312 0
Treatment: Drugs
Comparator / control treatment
Our standard of care for post endoscopic surgery entails the following:

- Oral antibiotics for 10 days post-op
- Saline irrigation 4 times per day
- Pulmicort irrigation once daily to start 2 weeks post-surgery
- Follow-up at 2-, 6- and 12-weeks post-op for naso-endoscopy
Control group
Active

Outcomes
Primary outcome [1] 327226 0
Primary outcome measure will be the subjective symptom scores via the SNOT-21 questionnaire.
Timepoint [1] 327226 0
The measurements are taken at 3 time points – 6 weeks, 12 weeks, and 18 weeks postoperatively. Timepoint 6 week and 18 weeks postoperatively are the primary timepoints.
Primary outcome [2] 327536 0
primary outcome measure will be the subjective symptom scores via the visual analogue scale of discomfort.
Timepoint [2] 327536 0
These measurements are taken at 3 time points – 6 weeks, 12 weeks, and 18 weeks postoperatively. Timepoint 6 week and 18 weeks postoperatively are the primary timepoints.
Primary outcome [3] 327537 0
primary outcome measures will be the endoscopy visual score via the Modified Lund Kenned Score.
Timepoint [3] 327537 0
These measurements are taken at 3 time points – 6 weeks, 12 weeks, and 18 weeks postoperatively. Timepoint 6 week and 18 weeks postoperatively are the primary timepoints.
Secondary outcome [1] 394285 0
Secondary outcome measure will be inflammatory cytokines collected from the mucus. the following cytokines will be assessed with the use of a human cytokine screening panel:

FGF basic
Eotaxin
G-CSF
GM-CSF
IFN-?
IL-1ß
IL-1ra
IL-2
IL-4
IL-5
IL-6
IL-7
IL-8
IL-9
IL-10
IL-12 (p70)
IL-13
IL-15
IL-17A
IP-10
MCP-1 (MCAF)
MIP-1a
MIP-1ß
PDGF-BB
RANTES
TNF-a
VEGF
Timepoint [1] 394285 0
Mucus samples will be collected from participants at 3 time points. Namely, at time of enrolment, at the post-operative visits 12- weeks and 18 weeks.
Secondary outcome [2] 395589 0
Secondary outcome measure will quantity of inflammatory cells collected from the mucus. This is an exploratory outcome. With the use of flow cytometry leukocytes will be assessed, including all major members of the innate lymphoid cell (ILC) family (ILC1s, ILC2s, and ILC3s), natural killer cells (NK cells),granulocytes (neutrophils and eosinophils), T-cells, and NKT-like cells.
Timepoint [2] 395589 0
Mucus samples will be collected from participants at 3 time points. Namely, at time of enrolment, at the post-operative visits 12- weeks and 18 weeks.

Eligibility
Key inclusion criteria
Participants who meet ALL the following criteria will be offered inclusion in the study:

• Those who have had symptoms of chronic rhinosinusitis that has been previously persistent for greater than 3 months
• Are over 18 years of age
• Are English speaking
• Can give written informed consent
• Have underwent endoscopic sinus surgery prior
• Have a phenotype of non-eCRS on histological assessment
• Disease control has not been established 6 weeks post-op
• Can commit to return to the clinic for 12- and 18-weeks postoperative endoscopic examination.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants who meet one the following criteria will be excluded from the study:
• Allergy to macrolides
• language other than English spoken
• Pregnant or breastfeeding
• History of cardiac disease
• Allergy to steroids
• Covid-19 positive

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 will be concealed and performed by an independent Pharmacy. The method will be a central randomisation by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created
by computer software (i.e. computerised sequence
generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
An a priori power calculation was run to determine the minimum sample size for the statistical analysis. The sample size calculation assumes a 95% level of confidence, a desired power level of 0.80, and an effect size based on previous studies between treatment groups (Cohen's d=0.675). Using these assumptions, the sample size required for this analysis was estimated to be 20. Assuming a dropout rate of 20% (patient dropping out at any point of the study will lead to the removal of all their measurements from the study), this gives a desired recruitment number of 48.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2022
Actual
Date of last participant enrolment
Anticipated
1/09/2023
Actual
Date of last data collection
Anticipated
1/01/2024
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 19162 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 33733 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 308383 0
Hospital
Name [1] 308383 0
The Queen Elizabeth Hospital, Department of Otolaryngology, Head and Neck Surgery.
Country [1] 308383 0
Australia
Primary sponsor type
Individual
Name
Professor Alkis Psaltis
Address
Department of Otorhinolaryngology, Head and Neck Surgery, The Queen Elizabeth Hospital
Tower block C, 28 Woodville Rd,
Woodville South SA 5011
Country
Australia
Secondary sponsor category [1] 309211 0
None
Name [1] 309211 0
Address [1] 309211 0
Country [1] 309211 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308348 0
CENTRAL ADELAIDE LOCAL HEALTH NETWORK HUMAN RESEARCH ETHICS COMMITTEE
Ethics committee address [1] 308348 0
Port Road
Adelaide SA 5000
Ethics committee country [1] 308348 0
Australia
Date submitted for ethics approval [1] 308348 0
30/04/2021
Approval date [1] 308348 0
13/05/2021
Ethics approval number [1] 308348 0
2021/HRE00162

Summary
Brief summary
The purpose of this study is to compare the addition of a low-dose antibiotic with properties that reduce inflammation to the therapy regimen after endoscopic surgery in chronic sinus disease, versus our current standard of care,
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110398 0
Prof Alkis Psaltis
Address 110398 0
Department of Otorhinolaryngology, Head and Neck Surgery, The Queen Elizabeth Hospital
Tower block C, 28 Woodville Rd,
Woodville South SA 5011
Country 110398 0
Australia
Phone 110398 0
+610882227158
Fax 110398 0
Email 110398 0
[email protected]
Contact person for public queries
Name 110399 0
Alkis Psaltis
Address 110399 0
Department of Otorhinolaryngology, Head and Neck Surgery, The Queen Elizabeth Hospital
Tower block C, 28 Woodville Rd,
Woodville South SA 5011
Country 110399 0
Australia
Phone 110399 0
+610882227158
Fax 110399 0
Email 110399 0
[email protected]
Contact person for scientific queries
Name 110400 0
Alkis Psaltis
Address 110400 0
Department of Otorhinolaryngology, Head and Neck Surgery, The Queen Elizabeth Hospital
Tower block C, 28 Woodville Rd,
Woodville South SA 5011
Country 110400 0
Australia
Phone 110400 0
+610882227158
Fax 110400 0
Email 110400 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
SNOT-22 scores
VAS scores
Inflammation markers
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
only researchers who provide a methodologically sound proposal
Available for what types of analyses?
for IPD meta-analyses
How or where can data be obtained?
access subject to approvals by Principal Investigator ([email protected]).


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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