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Trial registered on ANZCTR


Registration number
ACTRN12617000072314
Ethics application status
Approved
Date submitted
9/11/2016
Date registered
13/01/2017
Date last updated
27/11/2019
Date data sharing statement initially provided
27/11/2019
Date results information initially provided
27/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effect of chitosan-dextran (Chitodex) gel with budesonide and mupirocin in chronic rhinosinusitis patients post endoscopic sinonasal surgery
Scientific title
The effect of chitosan-dextran (Chitodex) gel with budesonide and mupirocin in chronic rhinosinusitis patients post endoscopic sinonasal surgery
Secondary ID [1] 290448 0
Nil Known
Universal Trial Number (UTN)
U1111-1189-3972
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Rhinosinusitis 300815 0
Condition category
Condition code
Infection 300637 300637 0 0
Other infectious diseases
Inflammatory and Immune System 300638 300638 0 0
Other inflammatory or immune system disorders
Respiratory 300639 300639 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients who meet ALL of the inclusion/exclusion criteria will be offered participation in this study and will be randomised into treatment and control group after informed consent has been obtained.

After patient has given consent, they will be randomised into one of three groups:
1. Test group 1: To receive Chitodex (10ml of succinyl chitosan + 300mg of dextran aldehyde) + Budesonide (Pulmicort) 2mg/4mL + Mupirocin 20mg OR
* Budesonide and Mupirocin is incorporated into the gel complex
2. Test group 2: Chitodex (10ml of succinyl chitosan + 300mg of dextran aldehyde) + Budesonide (Pulmicort) 2mg/4mL with oral antibiotics OR
* Budesonide is incorporated into the gel complex
3. Control group: Oral antibiotics and will not receive any test gel post op (current standard practice)

Oral antibiotics prescribed are as per standard post operative practice of investigator unless guided by previous swab results and contraindications (ie. adverse reactions).

All patients will have 2 swabs taken by the surgeon under direct visualisation with rigid nasoendoscopy prior to their endoscopic sinus surgery for both bacterial culture as well as nasal microbiome analysis. At the end of the sinus surgery while the patient is still under general anaesthetic, the gel will be applied as a once-off prodedure by the operating surgeon. The gel is injected into the sinonasal cavity as post operative wound dressing using a luer lock pressure control syringe.

All post operative and follow up instructions remain the same for patients in all cohorts.
The patients will then be asked to return to the outpatient department at 2 weeks, 6 weeks and 6 months post operation (none different to usual practice). At each review they will have 2 sinus swabs taken and a recording of their endoscopic sinus examination. The endoscopic video examination will then be scored by a blinded clinician for infection (pus), oedema, granulation tissue, and crusting using validated Lund Kennedy Scale. In addition, patients will be asked to complete a self-directed symptom and comfort questionnaire at each time-point SNOT22 and Visual Analogue Scale.

If on review visits any recruited patients have clinical signs and symptoms of sinus infection patient will be prescribed a rescue course of antibiotic (as per standard practice).
Intervention code [1] 296302 0
Treatment: Drugs
Comparator / control treatment
Control group patients are treated based on current standard practice which is to receive a course of oral antibiotics post endoscopic sinus surgery
Control group
Active

Outcomes
Primary outcome [1] 300048 0
The primary endpoint will be eradication of infection, indicated by a negative microbiology swab of the sinuses, clinical scores on endoscopy and symptom scores on patients’ self-directed questionnaires pre and post treatment.

The outcomes will be assessed by both the patient and an independent blinded clinician.

Pre and post treatment endoscopic scores will be performed by an independent blinded clinician using a scoring sheet specific for this study which consists of the validated Lund-Kennedy Endoscopic Score (LKES).

The patient will be scoring their pre and post symptoms using the VAS and SNOT-22 scoring sheet.
Timepoint [1] 300048 0
Sinus swab, endoscopy score and patient symptom scores will be assessed at baseline D0 of enrolment (pre-treatment) and at 2 weeks, 6 weeks and 6 months.
Secondary outcome [1] 329114 0
To observe the changes in nasal microbiome post endoscopic sinus surgery.
Nasal swabs are performed and uses culture-independent bacterial DNA sequencing techniques to identify the microbiome of sinonasal cavity
Timepoint [1] 329114 0
6 week post operation

Eligibility
Key inclusion criteria
Selection/inclusion criteria:
Patients who meet ALL of the following criteria will be offered inclusion in the study:
(1) Patients undergoing ESS for CRS AND
(2) Have who have had symptoms of chronic rhinosinusitis (nasal discharge, postnasal drip, nasal obstruction, facial pain and pressure, lack of sense of smell) that has been previously persistent for greater than 3 months AND
(3) are over 18 years of age AND
(4) are able to give written informed consent AND
(5) are local patients who will be returning to this centre for postoperative follow-up care
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) allergy to shellfish, steroids or mupirocin
(2) pregnant or breastfeeding
(3) immunodeficient patients (patients on any immunosuppressive or immunomodulatory agent)
(4) on other CYP450 inhibiting drugs (e.g. ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir and telithromycin)
(5) 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)
Allocation not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised by GraphPad Quickcalcs software (http://www.graphpad.com/quickcalcs/index.cfm) to be a part of either the test group 1, test group 2 or control group
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
Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
We will be recruiting a total of 57 patients for this study.

Power analysis estimates a sample size of 19 patients per arm would be required to achieve statistical significance (80%, p = 0.05), based on response rates of 25% in control group and 70% in treatment group, as well as accounting for a 10% drop out rate.

This 70% treatment response rate may represent an underestimation as previous study conducted showed 88.9% of patients were culture negative following mupirocin sinus rinses (Jervis-Bardy et al, 2012). We have done this because it would be the first time we would be using Chitodex gel as a drug vehicle for Mupirocin and by doing so it would increase our probability of detecting smaller clinical responses. For the control group, the 25% response rate estimation is based on clinical observation that chronically infected patients have responded poorly to conventional therapy.


All results will be statistically analysed at the completion of the study. The proposed statistical test will be 2-way analysis of variance (ANOVA) and Student’s t-test, with a significance value set at p<0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
1/11/2016
Date of last participant enrolment
Anticipated
1/11/2018
Actual
1/11/2018
Date of last data collection
Anticipated
1/05/2019
Actual
1/05/2019
Sample size
Target
57
Accrual to date
Final
57
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 6907 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [2] 6908 0
Memorial Hospital - North Adelaide
Recruitment postcode(s) [1] 14577 0
5006 - North Adelaide
Recruitment postcode(s) [2] 14576 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 294915 0
University
Name [1] 294915 0
University of Adelaide
Country [1] 294915 0
Australia
Primary sponsor type
Hospital
Name
The Queen Elizabeth Hospital
Address
The Queen Elizabeth Hospital
28 Woodville Rd,
Woodville South, 5011
South Australia, Australia
Country
Australia
Secondary sponsor category [1] 293748 0
None
Name [1] 293748 0
None
Address [1] 293748 0
None
Country [1] 293748 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296292 0
The Queen Elizabeth Hospital, Lyell McEwin Hospital and Modbury Hospital HREC
Ethics committee address [1] 296292 0
The Queen Elizabeth Hospital
Ethics: DX465101
Ground Floor, Basil Hetzel Institute
28 Woodville Road
WOODVILLE SOUTH SA 5011
Ethics committee country [1] 296292 0
Australia
Date submitted for ethics approval [1] 296292 0
30/09/2015
Approval date [1] 296292 0
31/10/2016
Ethics approval number [1] 296292 0
HREC/15/TQEH/174 Q20161009

Summary
Brief summary
This research is aimed at improving outcomes for patients with chronic rhinosinusitis post endoscopic sinus surgery. A dissolvable dressing Chitodex (CD) gel has already been known to be beneficial to postoperative bleeding and healing after endoscopic sinus surgery. We aim to further improve its effects by combining the current formulation with budesonide (a steroid solution) and mupirocin (an antibacterial agent).

We have specifically targeted patients in the immediate post endoscopic sinus surgery setting because in previous studies, we have found that biofilm-positive patients compared to biofilm-negative patients have worse outcome post surgery in both symptoms and nasoendoscopy scores, requiring repeated courses of antibiotic treatment and extra postoperative visits (Singhal et al 2008).

Therefore in this study we hope to investigate if the eradication of biofilms combined with the improved wound healing properties of using Chitodex gel incorporated with mupirocin and budesonide (CBM gel) could prevent patients from progressing to the subset of recalcitrant disease.

The specific aims of this study is to
1. To investigate the effects of Chitodex + Budesonide + Mupirocin (CBM) gel in post sinonasal surgery patients with chronic rhinosinusitis (CRS)
2. Compare the change in nasal microbiome post endoscopic sinus surgery

The primary end point is measured by:
1) Eradication of bacteria confirmed with microbiological swab
2) Independently scored video endoscopic examination of sinuses pre and post treatment
3) Patient's symptoms score pre and post treatment

The secondary end point is to:
1. Compare the change in nasal microbiome post endoscopic sinus surgery
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 70126 0
Prof Peter John Wormald
Address 70126 0
Department of Otorhinolaryngology
The Queen Elizabeth Hospital
28 Woodville Rd,
Woodville South 5011
South Australia
Australia
Country 70126 0
New Zealand
Phone 70126 0
+61 8 8222 7158
Fax 70126 0
Email 70126 0
peterj.wormald@adelaide.edu.au
Contact person for public queries
Name 70127 0
Dr Mian Ooi
Address 70127 0
The Queen Elizabeth Hospital
28 Woodville Rd,
Woodville South 5011
South Australia
Australia
Country 70127 0
Australia
Phone 70127 0
+618 8222 7158
Fax 70127 0
Email 70127 0
mianli.ooi@gmail.com
Contact person for scientific queries
Name 70128 0
Dr Mian Ooi
Address 70128 0
The Queen Elizabeth Hospital
28 Woodville Rd,
Woodville South 5011
South Australia
Australia
Country 70128 0
Australia
Phone 70128 0
+618 8222 7158
Fax 70128 0
Email 70128 0
mianli.ooi@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.