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Trial registered on ANZCTR


Registration number
ACTRN12621001058864
Ethics application status
Approved
Date submitted
30/04/2021
Date registered
11/08/2021
Date last updated
30/08/2024
Date data sharing statement initially provided
11/08/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of Chitodex gel in ear drum repair (tympanoplasty) surgery
Scientific title
A single-blinded randomised trial evaluating the efficacy of chitosan-dextran (Chitodex) gel versus Gelfoam sponge instillation within the middle ear and external auditory canal during tympanoplasty surgery
Secondary ID [1] 312856 0
NCT06260618
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
tympanic membrane perforation 321765 0
ear drum repair surgery 322425 0
tympanoplasty surgery 322426 0
Mastoid surgery 334992 0
Condition category
Condition code
Ear 319503 319503 0 0
Other ear disorders
Surgery 320078 320078 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The general purpose of this study is to compare Chitosan-dextran (Chitodex) gel versus current standard of care, Gelfoam, as a middle ear (ME) and external auditory canal (EAC) packing agent as part of tympanoplasty and mastoidectomy procedures to close tympanic membrane perforations (TMP).

We aim to compare the success rates of tympanoplasty/mastoidectomy surgery between the two products and to identify the ME packing agent-of-choice to ensure TMP closure as well as minimal inflammation of the middle ear mucosa.

The most critical measure of success during tympanoplasty and mastoidectomy surgery is the closure of a chronic, pre-existing TMP. As such, our primary outcome will be a measure of tympanic membrane closure. This is performed under direct vision during routine post-operative surveillance via the use of either a hand-held otoscope or an operating otologic microscope. We will aim to perform this check at 4 distinct time-points: 2 and 6 weeks post-op, 3 months post-op and 6 months post-op.

Chitosan-dextran gel is packaged within a syringe and has a cannula attached, much like the Gelfoam syringe system. Approx 3-5mL of product is applied during the surgery. Approx 2mL into the middle ear, as a support material for the graft. After graft suturing is complete, another 3mL (approx) is applied into the external ear canal as a packing agent. This is the same procedure as Gelfoam is currently used for this purpose.

The surgeon will administer the gel during the surgery as they would with the standard of care Gelfoam. The product comes in a sterile kit to be opened by Scrub Nurse.

Fidelity of the interventions is measured in several ways by the surgeon at the end of the operation. A good seal for the graft is always assessed for by the surgeon prior to completing any tympanoplasty. This is determined via any evidence of air escape from the middle ear when palpating the tympanic membrane and graft at the end of the procedure. A good seal indicates a well-positioned graft. The surgeon’s operative notes will indicate this. We will also obtain endoscopic images and videos at the end of procedure to assess positioning of the graft.
Intervention code [1] 320424 0
Treatment: Devices
Comparator / control treatment
The current standard of care in middle ear packing material has been Gelfoam, Gelfoam is an absorbable gelatin sponge manufactured from denatured porcine skin. Generally, Gelfoam resides within the middle ear for 2 to 9 weeks prior to being degraded via phagocytosis.

A single Gelfoam sponge is divided into small pieces and used within the ear. One piece of Gelfoam can typically be cut into over 200 smaller pieces. We use approximately 10 to 20 of these smaller pieces per surgery. Approx a third of the product is applied into the middle ear, as a support material for the graft. After graft suturing is complete, the remaining two thirds are applied into the external ear canal as a packing agent.

The surgeon administers the foam during the surgery as they would with the standard TMP repair surgery. The product comes in a sterile package to be opened and cut up by Scrub Nurse.

Control group
Active

Outcomes
Primary outcome [1] 327365 0
tympanic membrane closure assessed via otoscopy (images will be captured via the otoscopic equipment)
Timepoint [1] 327365 0
2 weeks post-operatively
6 weeks post-operatively
3 months post-operatively (primary timepoint)
6 months post-operatively
Secondary outcome [1] 394812 0
Audiogram hearing assessment

An audiogram is a standardised assessment of hearing that has been utilised in routine clinical practice for many decades. It measures hearing thresholds in decibels over a range of noise frequencies from 200Hz up to 8000Hz. It is always performed in a sound-proof room with over ear headphones.
Timepoint [1] 394812 0
2 weeks post-operatively
6 weeks post-operatively
3 months post-operatively
6 months post-operatively
Secondary outcome [2] 394813 0
tympanometry evaluation to assess eardrum function.

Tympanometry tests how well the eardrum moves. The audiologist will put a small probe into the ear. A small device attached to the probe will push air into your ear. The output from the probe is translated to a graph called a tympanogram.
Timepoint [2] 394813 0
3 months post-operatively
6 months post-operatively
Secondary outcome [3] 394814 0
surgeon's feedback - ease of use of product

We will be questioning the ease of which to place the packing material within the anterior mesotympanum as well as the ease with which adequate graft positioning was obtained at the end of surgery. This will be done on a 7-point Likert scale with 1 been very difficult and 7 being very easy to use.
Timepoint [3] 394814 0
Once, post-operatively. After the surgeon has finished the surgery, the trial staff will collect this score from the surgeon within 24 hours of the surgery.
Secondary outcome [4] 394815 0
ease of use of product - timing the surgeries

Start and finish times for all surgeries is clocked into the hospital peri-operative software by the nursing staff in real time. This is a routine part of modern peri-operative care. These records can be retrieved to establish the total operating time of each surgery.
Timepoint [4] 394815 0
Once, peri-operatively
Secondary outcome [5] 394816 0
participant subjective symptom score/questionnaire.

As there is no current validated questionnaire to assess post-tympanoplasty subjective symptoms, a modified/shorter version of a validated test has been designed for this study..
The Chronic Otitis Media Outcomes Test (COMOT-15 test) including a score for (left and right); hearing, ear discharge, ear pain, ear fullness, tinnitus (ringing in the ears), vertigo, overall ear health, overall impact on quality of life.
These same questions have been used widely in the literature.
Timepoint [5] 394816 0
2 weeks post-operatively
6 weeks post-operatively
3 months post-operatively
6 months post-operatively
Secondary outcome [6] 439246 0
Clearance of middle ear. This is to be measured by MRI - Axial T2 weighted with fat suppression at 3mm intervals
Timepoint [6] 439246 0
Secondary outcome [7] 439247 0
Clearance of middle ear. This is to be measured by MRI - Axial T2 weighted with fat suppression at 3mm intervals
Timepoint [7] 439247 0
28 days post-operatively

Eligibility
Key inclusion criteria
Participants who meet ALL of the following criteria will be considered for inclusion:
1. Individuals who have otoscopic evidence of tympanic membrane perforation that is also confirmed by tympanometry (Defined as a Type B tympanogram, with elevated EAC volume) AND
2. The TM perforation is associated with at least 15dB of conductive hearing loss on the affected side AND
3. Are indicated to undergo closure of the perforation via tympanoplasty surgery
4. OR Individuals who are indicated for ossiculoplasty due to ossicular chain disruption and it’s sequelae
5. OR Individuals who are indicated for mastoidectomy for COM or its sequelae eg cholesteatoma
6. Demonstrate healthy, dry middle ear mucosal cavities at time of surgery AND
7. Are 18 years of age or over AND
8. Are able to give written informed consent AND
9. Are committed to returning for post-operative assessments at 2 and 6 weeks post-op, 3-, and 6- months post-op, and an MRI 4 weeks post-op
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Operative ear is the better or only hearing ear
2. dysfunction during otoscopic and tympanometric examination
3. Known allergy to shellfish or ciprofloxacin antibiotics
4. Pregnant or breastfeeding
5. Hepatitis, HIV or any blood disorders
6. COVID-19 positive patients
7. Contra indications for MRI

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 involved contacting the holder of the allocation schedule who was "off-site" or at central administration site.
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
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Minimal sample size for our study was calculated using the following parameters. We assume a 95% confidence level, with desired power of 0.85 in a non-inferiority model that accepts a limit of 20%.
Using these assumptions, the calculated sample size required was estimated at 33. Factoring in a total predicted drop-out rate of 20%, we have determined a recruitment size as follows; 33/(1-0.2)= 41.25, or n=42 rounded up), times 2 arms = 84 participants.

Comparing primary outcome of perforation closure success rates between Chitodex and Gelfoam will be a binary measure at the 2, 6 week and 3, 6-month OPD visits. Determination of differences in closure rates between the two groups will be determined using the Fisher’s exact test.
Audiometric outcomes via average pure-tone audiometry results spanning between 500Hz and 4kHz will be measured for patients in both groups preoperatively as well as at 3 and 6 months post-operatively. Analysis of hearing thresholds (dB) between groups and time-points will be via a One-Way ANOVA, utilising “treatment” and “time” as independent variables to measure the dependent variable of “hearing threshold.”
One-way ANOVA will also be utilised for analysis of operative time between treatment groups, factoring multiple dependent variables of “treatment,” “surgeon” and “surgical approach.”
Remaining Likert scale outcomes are to be compared using Student’s t-tests.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/09/2021
Actual
20/11/2021
Date of last participant enrolment
Anticipated
6/06/2025
Actual
Date of last data collection
Anticipated
6/09/2025
Actual
Sample size
Target
84
Accrual to date
24
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 19244 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [2] 19245 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [3] 19246 0
Calvary Wakefield Hospital - Adelaide
Recruitment hospital [4] 19247 0
Calvary North Adelaide Hospital - North Adelaide
Recruitment hospital [5] 19248 0
Flinders Private Hospital - Bedford Park
Recruitment hospital [6] 19249 0
Memorial Hospital - North Adelaide
Recruitment postcode(s) [1] 33820 0
5011 - Woodville
Recruitment postcode(s) [2] 33821 0
5112 - Elizabeth Vale
Recruitment postcode(s) [3] 33822 0
5000 - Adelaide
Recruitment postcode(s) [4] 33823 0
5006 - North Adelaide
Recruitment postcode(s) [5] 33824 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 308479 0
Self funded/Unfunded
Name [1] 308479 0
Professor Peter-John Wormald
Country [1] 308479 0
Australia
Primary sponsor type
Government body
Name
Central Adelaide Local Health Network (CALHN)
Address
The Queen Elizabeth Hospital
Department of Otolaryngology, Head and Neck Surgery
Tower Block 3C
37 Woodville Road
Woodville South SA 5011
Country
Australia
Secondary sponsor category [1] 309331 0
Other
Name [1] 309331 0
The ENT Research Institute Pty Ltd
Address [1] 309331 0
The Queen Elizabeth Hospital
Department of Otolaryngology, Head and Neck Surgery
Tower Block 3C
37 Woodville Road
Woodville South SA 5011
Country [1] 309331 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308432 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 308432 0
Ethics committee country [1] 308432 0
Australia
Date submitted for ethics approval [1] 308432 0
16/02/2021
Approval date [1] 308432 0
13/05/2021
Ethics approval number [1] 308432 0
2021/HRE00065

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110690 0
Prof Peter-John Wormald
Address 110690 0
The Queen Elizabeth Hospital
Department of Otolaryngology, Head and Neck Surgery
Tower Block 3C
37 Woodville Road
Woodville South SA 5011
Country 110690 0
Australia
Phone 110690 0
+61 0882227158
Fax 110690 0
Email 110690 0
[email protected]
Contact person for public queries
Name 110691 0
Emma Barry
Address 110691 0
The Queen Elizabeth Hospital
Department of Otolaryngology, Head and Neck Surgery
Tower Block 3C
37 Woodville Road
Woodville South SA 5011
Country 110691 0
Australia
Phone 110691 0
+61 0881334004
Fax 110691 0
Email 110691 0
[email protected]
Contact person for scientific queries
Name 110692 0
Emma Barry
Address 110692 0
The Queen Elizabeth Hospital
Department of Otolaryngology, Head and Neck Surgery
Tower Block 3C
37 Woodville Road
Woodville South SA 5011
Country 110692 0
Australia
Phone 110692 0
+61 0881334004
Fax 110692 0
Email 110692 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
undecided.
Data will likely be pooled and published in a scientific journal article
Relatively small study with 2 arms, individual data would unlikely be valuable to other researchers


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.