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Trial registered on ANZCTR


Registration number
ACTRN12616000329460
Ethics application status
Approved
Date submitted
17/02/2016
Date registered
14/03/2016
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
Prospectively registered

Titles & IDs
Public title
The effect of chitosan-dextran (Chitodex) gel with budesonide and mupirocin on recalcitrant rhinosinusitis
Scientific title
The effect of chitosan-dextran (Chitodex) gel with budesonide and mupirocin on recalcitrant rhinosinusitis
Secondary ID [1] 288482 0
Nil
Universal Trial Number (UTN)
U1111-1179-2162
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Rhinosinusitis 297535 0
Condition category
Condition code
Infection 297734 297734 0 0
Other infectious diseases
Inflammatory and Immune System 297735 297735 0 0
Other inflammatory or immune system disorders
Respiratory 298127 298127 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.

Under endoscopic guidance, test group patients will have a sinus swab performed, followed by 10mls of the Chitodex+budesonide+mupirocin (CBM) complex applied to each side of their sinuses (total 20mls of CBM gel in one patient) by the surgeon. This is experimental practice. The treatment gel consists of 10mL 5% chitodex + 2mL buffered saline + 2mg/4mL budesonide + 10mg/4mL mupirocin (total dose for bilateral sinus cavity). This will be applied under direct visual endoscopic guidance by the surgeon to ensure all sinus cavities are filled with gel and will add approximately an additional 15 minutes to the patient's usual appointment.

Patients in the control group will be given culture sensitive oral antibiotics. This is usual practice.

The patient will be asked to return to the outpatient department 7 days later for a repeat sinus swab and a recording of their endoscopic sinus examination. The endoscopic video examination will then be scored by a blinded independent clinician for infection (pus), oedema, granulation tissue, and crusting using a standardised scale which are the study outcomes of this study. In addition, patients will be asked to complete a self-directed symptom and comfort questionnaire at each time-point.

If there are signs of persistent infection at 7 days post-application of the CBM complex, then a second swab will be taken and sent for repeat microbiological evaluation. Patients who were in the CBM group will receive another 10ml dose of CBM applied endoscopically by the surgeon into each side of their sinus cavity and patients who were in the control group will be swapped over to the gel group.

If there are no further clinical signs of infection at the 1 or 2 week post-recruitment visit, the patient will have a final microbiology swab taken to confirm eradication of infection and would be considered as having completed the study. If the patient has still not improved after 14 days, they will resume usual outpatient/surgical care for their symptoms.
Intervention code [1] 293833 0
Treatment: Drugs
Comparator / control treatment
Control group patients are treated based on current standard practice which is to receive a course of culture sensitive oral antibiotics.
Control group
Active

Outcomes
Primary outcome [1] 297388 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) with the addition of an evidence of infection section.

The patient will be scoring their pre and post symptoms using the VAS and SNOT-22 scoring sheet.
Timepoint [1] 297388 0
Sinus swab, endoscopy score and patient symptom scores will be assessed at baseline D0 of enrolment (pre-treatment) and at Day 7 +/- 2 days (post treatment).
Secondary outcome [1] 320929 0
Secondary outcomes will be patient comfort/discomfort following application of the gel compared to control (oral antibiotics) using a 5-point Likert Scale.
Timepoint [1] 320929 0
Post Treatment. Day 7 +/- 2 days.

Eligibility
Key inclusion criteria
Selection/inclusion criteria:
Patients who meet ALL of the following criteria will be offered inclusion in the study:
(1) Those 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
(2) have had at least one operation for their chronic rhinosinusitis > 12 weeks prior to enrolment AND
(3) continue to have ongoing symptoms despite surgical management AND
(4) have not responded to at least one course of oral antibiotics
(5) have a positive sinonasal swab that indicates infection of the sinuses AND
(6) are over 18 years of age AND
(7) are able to give written informed consent AND
(8) are local patients who will be returning to this centre for postoperative 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) 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 or control group
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
After signing the consent form, participants will be randomised into one of two treatment groups:
1. Test group, participants will receive Chitodex + Budesonide + Mupirocin gel applied to their sinuses by surgeon OR
2. Control group, participants will receive oral antibiotics appropriate to their infection for 7 days

At the end of the 7 day treatment participants will be re-assesses. If their infection has resolved, they would have completed the study.

If participants have not improved and were in the:
1. Test group, they will receive another dose of the Chitodex + Budesonide (steroid) + Mupirocin (antibacterial agent) gel
2. Control group, they will be swapped over to the test group to receive a dose of the Chitodex + Budesonide (steroid) + Mupirocin (antibacterial agent) gel
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
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.

Power analysis estimates a sample size of 19 patients per arm would be required (total patients to be recruited is 38) 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.

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 postcode(s) [1] 12748 0
5011 - Woodville South

Funding & Sponsors
Funding source category [1] 292907 0
University
Name [1] 292907 0
The University of Adelaide, Dept of Surgery
Address [1] 292907 0
Department Otorhinolaryngology
3C Level 3 Main Building, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville 5011, South Australia, Australia
Country [1] 292907 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] 291662 0
None
Name [1] 291662 0
N/A
Address [1] 291662 0
N/A
Country [1] 291662 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294419 0
The Queen Elizabeth Hospital, Lyell McEwin Hospital and Modbury Hospital HREC
Ethics committee address [1] 294419 0
The Queen Elizabeth Hospital
Ethics: DX465101
Ground Floor, Basil Hetzel Institute
28 Woodville Road
WOODVILLE SOUTH SA 5011
Ethics committee country [1] 294419 0
Australia
Date submitted for ethics approval [1] 294419 0
07/09/2015
Approval date [1] 294419 0
28/01/2016
Ethics approval number [1] 294419 0
HREC/15/TQEH/173

Summary
Brief summary
This research is aimed at improving outcomes for patients with chronic rhinosinusitis, particularly the cohort of patients who experience persistent CRS symptoms despite optimum medical and surgical therapy, termed as recalcitrant CRS (rCRS).

We hope that we are able to developed an agent that could help manage persistent infections in patients with chronic rhinosinusitis even after they have had surgery and potentially improve patient's symptoms and reduce the need for revision surgery.

The primary end point of this study is to:
1. To assess the efficacy of Chitodex-Budesonide-Mupirocin gel in treating patients with recalcitrant chronic rhinosinusitits
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 of this study is to:
1. Assess the tolerability of the treatment gel vs oral antibiotics


Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63198 0
Prof Peter-John Wormald
Address 63198 0
Department of Otorhinolaryngology
The Queen Elizabeth Hospital
28 Woodville Rd,
Woodville South 5011
South Australia
Australia
Country 63198 0
Australia
Phone 63198 0
+61 8 8222 7158
Fax 63198 0
Email 63198 0
peterj.wormald@adelaide.edu.au
Contact person for public queries
Name 63199 0
Dr Mian Ooi
Address 63199 0
The Queen Elizabeth Hospital
28 Woodville Rd,
Woodville South 5011
South Australia
Australia
Country 63199 0
Australia
Phone 63199 0
+61 8 8222 7158
Fax 63199 0
Email 63199 0
mianli.ooi@gmail.com
Contact person for scientific queries
Name 63200 0
Dr Mian Ooi
Address 63200 0
The Queen Elizabeth Hospital
28 Woodville Rd,
Woodville South 5011
South Australia
Australia
Country 63200 0
Australia
Phone 63200 0
+61 8 8222 7158
Fax 63200 0
Email 63200 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?
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?
Results – basic reporting
Results – plain English summary