Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000577213
Ethics application status
Approved
Date submitted
16/03/2018
Date registered
16/04/2018
Date last updated
16/04/2019
Date data sharing statement initially provided
16/04/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effect of novel drug with Chitodex gel on wound healing post endoscopic sinus surgery in the treatment of Chronic Rhinosinusitis (CRS)
Scientific title
Chitosan-dextran (Chitodex) gel with and without Deferiprone and Gallium-Protoporphyrin-wound healing and post operative outcomes in the treatment of Chronic Rhinosinusitis (CRS)
Secondary ID [1] 294350 0
TGA: CT-2017-CTN-04279-1 v1
Universal Trial Number (UTN)
U1111-1211-0391
Trial acronym
CDG CT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Rhino-Sinusitis 307072 0
Chronic recalcitrant sinusitis 307073 0
Condition category
Condition code
Surgery 306182 306182 0 0
Other surgery
Infection 306255 306255 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
FESS(Functional Endoscopic Sinus Surgery) alone (consisting 4 arms)

Arm 1- Dissolvable nasal dressing (Chitodex gel: CD-gel) alone- 10 ml of CD gel applied in the operated sinus, only once immediately at the end of surgery.

Arm 2-CD gel with the iron chelator Deferiprone(20mM/ml-)10 ml of CD gel with Deferiporone applied in the operated sinus, only once immediately at the end of surgery.

Arm 3- CD gel with the iron chelator Deferiprone(20mM/ml and the antibacterial agent Gallium-Protoporphyrin(250 µg/ml) -.10 ml of CD gel applied in the operated sinus, only once immediately at the end of surgery

Arm 4 - CD gel + GaPP the antibacterial agent Gallium-Protoporphyrin(250 µg/ml) - 10 ml of CD gel with drug applied in the operated sinus, only once immediately at the end of surgery

in FESS + drill out ( consisting 5 arms) 20 ml of CD gel applied in the frontal sinus, only once immediately at the end of surgery just as 4 arms of FESS group and

Arm 5- Saline control

All patients will undergo complete blood counts , Serum Iron levels and Liver funtion test before application. Post-operatively the serum drug levels of Deferiporone & Gallium Protoporphyrin willbe evaluated at 2 hrs, 6 hrs and 2 weeks . They will also be watched for development of any symptoms of photosensitivity.
Intervention code [1] 300652 0
Treatment: Surgery
Intervention code [2] 300653 0
Treatment: Devices
Intervention code [3] 300694 0
Treatment: Drugs
Comparator / control treatment
The trial has 2 sets of patients;
1. FESS only group-and One side of the sinuses is control ( routine saline nasal douching)

2.FESS + drill out- 10 participants controls (saline nasal douching would used as treatment).
Control group
Active

Outcomes
Primary outcome [1] 305190 0
Stenosis of the sinus ostea as measured by a probe on endoscopic examination post operatively and followed up by endoscopic examinaion at 12 weeks.

12 week is the primary end point to measure outcomes.
Timepoint [1] 305190 0
Base line at time of surgery

12 weeks post surgery review
Secondary outcome [1] 344459 0
Secondary outcomes will be eradication of infection indicated by a negative microbiology swab of the sinuses.
Timepoint [1] 344459 0
12 weeks post surgery review nasal swab culture
Secondary outcome [2] 345057 0
ORDINAL SCALE MEASUREMENT: Adhesion of Middle turbinate to medial wall on right and left side in percentages  as assesed by endoscopic examination:
0%,
1-25%,
26-50% or
more than 50%
Timepoint [2] 345057 0
12 weeks
Secondary outcome [3] 345502 0
Mucosal odema( 0-3) on endoscopic examination
0 being no visible mucosal odema
1 mild mucosal odema without oblitartion of the ethmoid cavity
2-severe mucosal odema oblitrating most of the ethmoid
3-Frank polyposis
Timepoint [3] 345502 0
0 weeks, 2 weeks post post operative, 6 weeks post operative and 12 weeks post operative
Secondary outcome [4] 345503 0
Crusting(0-2) on endoscopic examination
0-Absent
1-,Mild,
2-Severe
Timepoint [4] 345503 0
0 weeks, 2 weeks post post operative, 6 weeks post operative and 12 weeks post operative
Secondary outcome [5] 345504 0
Granulations(0-3) on endoscopic examination
0-absent
1-mild
2-moderate
3-severe
Timepoint [5] 345504 0
0 weeks, 2 weeks post post operative, 6 weeks post operative and 12 weeks post operative
Secondary outcome [6] 345505 0
Visual analouge scale(subjective score done by the patients on right and left side seperately)
Facial Pain/Discomfort: 0 is no pain or discomfort, 10 is the worst pain theyhave ever experienced
Timepoint [6] 345505 0
0 weeks, 2 weeks post post operative, 6 weeks post operative and 12 weeks post operative
Secondary outcome [7] 345506 0
Bleeding: 0 is no bleeding, 10 is bleeding requiring re-operation to control it
Timepoint [7] 345506 0
0 weeks, 2 weeks post post operative, 6 weeks post operative and 12 weeks post operative
Secondary outcome [8] 345507 0
Nasal Obstruction: 0 is a perfect airway which is very easy to breathe through, 10 is completely blocked with no air movement through that side.
Timepoint [8] 345507 0
0 weeks, 2 weeks post post operative, 6 weeks post operative and 12 weeks post operative
Secondary outcome [9] 345508 0
Nasal Secretion/throat drip: 0 is no nasal secretions, 10 is copious secretions with con-stant nasal dripping.
Throat drip: 0 is no nasal secretions, 10 is copious secretions with constant nasal drip-ping.
Timepoint [9] 345508 0
0 weeks, 2 weeks post post operative, 6 weeks post operative and 12 weeks post operative
Secondary outcome [10] 345509 0
Sense of smell: 0 is no smell ability at all, 10 is best smell ability.
Timepoint [10] 345509 0
0 weeks, 2 weeks post post operative, 6 weeks post operative and 12 weeks post operative
Secondary outcome [11] 345510 0
Patient Chronic Sinusitis symptom severeity is measured subjectively using the SNOTT 22 score (a standardised questionare consisteing of 22 questions which describe the symptoms of a patients in scale of 0 to 5 , o being no symptoms and 5 being severe symptoms).
Timepoint [11] 345510 0
0 weeks and 12 weeks post operative

Eligibility
Key inclusion criteria
Participants who meet ALL of the following criteria will be offered inclusion in the study:
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
are over 18 years of age AND
are able to give written informed consent AND
are local and who will be returning to this centre for postoperative follow-up care AND
are indicated to undergo endoscopic sinus surgery and willing to return at 2, 6 & 12 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. allergy to shellfish
2. pregnant or breastfeeding
3. Hepatitis or blood disorders.
4.any drug allergy

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 was not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A stratified, block randomization procedure will be employed to ensure equal numbers of patients who underwent ESS and ESS+frontal drill out in each of the treatment groups. This will employ a 2 (procedure) by 3 (treatment groups) stratification design with 10 patients randomized to each of the six cells. Further stratification will randomise each group of 10 patients so that 5 receive the procedure on the left nostril and 5 receive it on the right nostril. This is to ensure that site of procedure (left or right nostril ) does not confound the results. A similar group of 10 patients undergoing FESS + drill out would be recruited as controls where only saline would used as treatment
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 1
Type of endpoint/s
Efficacy
Statistical methods / analysis
Power calculations were based on the requirement that effects be assessed at the 5% alpha level with 80% statistical power. The outcomes are measured based on the wound healing in the sinus openings made during surgery. We have determined that a clinically meaningful difference between the two closest treatment groups would be a minimal difference of 3 mm2 area in the frontal ostial size at 12 weeks post-surgery. Based on available data, we would expect the standard deviation to be approximately ½ the magnitude of the mean difference (i.e.: 1.5). In this study, observations over time may be correlated due to clustering within nostril and patient. This would result in an under estimate of the variance with a consequent increase in the risk of a type 1 error. We have inflated the estimated standard deviation by a factor of 1.5 (i.e.: 1.5 * 1.5 = 2.25) to account for this. Following this adjustment, a sample of 1 patients per treatment arm would be required.
Analysis: Continuous measures will be summarized as means with standard deviations or medians with inter-quartile range as appropriate. Categorical measures will be summarized with counts and percentages. The descriptive statistics will be reported with stratification by treatment arm. Differences over time will be assessed using linear mixed effects models with participants treated as a random factor. All tests will be two-tailed and assessed at the 5% alpha level.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
14/02/2018
Date of last participant enrolment
Anticipated
1/09/2022
Actual
Date of last data collection
Anticipated
30/11/2022
Actual
Sample size
Target
90
Accrual to date
10
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 10398 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 22078 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 298992 0
University
Name [1] 298992 0
The University of Adelaide
Country [1] 298992 0
Australia
Primary sponsor type
University
Name
The University of Adelaide
Address
Adelaide, South Australia
5005 Australia
Country
Australia
Secondary sponsor category [1] 298216 0
None
Name [1] 298216 0
Address [1] 298216 0
Country [1] 298216 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299921 0
CALHN Human Research Ethics Committee
Ethics committee address [1] 299921 0
Level 3, Roma Mitchell House
136 North Terrace
Adelaide, South Australia, 5000
Ethics committee country [1] 299921 0
Australia
Date submitted for ethics approval [1] 299921 0
24/10/2017
Approval date [1] 299921 0
21/12/2017
Ethics approval number [1] 299921 0
HREC/17/TQEH/245

Summary
Brief summary
This research project is testing a new treatment for chronic rhinosinusitis by the use of a Chitosan-Dextran (Chitodex) gel mixed with medications to see if there is improved healing after sinus surgery and less infection.

Chronic rhinosinusitis affects approximately 15% of the general population and is characterised by sinusitis symptoms persisting for more than 3 months. Patients who do not respond adequately to oral and topical steroids, antibiotics and nasal lavage require surgical management. The surgical procedure is termed endoscopic sinus surgery, and involves removing oedematous mucosa, pus and debris, as well as clearance of bony walls within the sinonasal cavity to open up blocked sinuses. Participants will receive the standard hospital information sheet about the sinus surgery, and will sign the standard hospital consent form for the sinus surgery.

Purpose: The purpose of this research project is testing in sinus surgery whether adding two new antimicrobial agents (Deferiprone and Gallium-Protoporphyrin ) to a locally developed dissolvable nasal dressing (Chitodex gel) will improve the anti-microbial and wound-healing effects of Chitodex gel after sinus surgery compared to Chitodex alone.

Procedure and Treatment: Under endoscopic guidance, each participant will have a sinus swab performed prior to surgery and then undergo the planned sinus surgery- Endoscopic sinus surgery (ESS) or ESS with frontal drill out

At the end of the procedure, each participant will receive 10 ml of gel (Chitodex or Chitodex+ Deferiprone or Chitodex+ Deferiprone+ Gallium-Protoporphyrin) into one side of each of the three sinuses and the untreated side would be referred to as the control and receive routine standard of care.
If the surgery is meant to produce a larger frontal sinus cavity (ESS with frontal drillout) 20 ml of gel would be applied or 20 ml of saline if you are in the control group.
Post-operative care will proceed as per standard care after sinus surgery.

Participants will return to the outpatient department 2 weeks, 6 weeks and 12 weeks after the surgery for post-operative review. During each visit we would perform a sinus swab and an endoscopic video recording of the sinuses.

The recorded video examination will then be scored by an independent clinician, unaware of your treatment, for infection (pus), oedema, granulation tissue, and crusting using a standardised scoring scales.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81994 0
Prof Peter John Wormald
Address 81994 0
Department Of ENT, Head Neck & Skull Base Surgery
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South SA 5011
Country 81994 0
Australia
Phone 81994 0
+61882227158
Fax 81994 0
+61882227419
Email 81994 0
peterj.wormald@adelaide.edu.au
Contact person for public queries
Name 81995 0
A/Prof Rajan Sundaresan Vediappan
Address 81995 0
Department Of ENT, Head Neck & Skull Base Surgery
The Queen Elizabeth Hospital/Basil Hetzel Institute
28 Woodville Road
Woodville South
SA 5011
Country 81995 0
Australia
Phone 81995 0
+61882227158
Fax 81995 0
61882227419
Email 81995 0
rajan.vediappan@adelaide.edu.au
Contact person for scientific queries
Name 81996 0
A/Prof Rajan Sundaresan Vediappan
Address 81996 0
Department Of ENT, Head Neck & Skull Base Surgery
The Queen Elizabeth Hospital/Basil Hetzel Institute
28 Woodville Road
Woodville South
SA 5011
Country 81996 0
Australia
Phone 81996 0
+61882227158
Fax 81996 0
61882227419
Email 81996 0
rajan.vediappan@adelaide.edu.au

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


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23615Ethical approval    374734-(Uploaded-21-04-2021-11-54-17)-Study-related document.pdf

Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseChitogel following endoscopic sinus surgery promotes a healthy microbiome and reduces postoperative infections.2022https://dx.doi.org/10.1002/alr.23001
Dimensions AITackling superbugs in their slime castles: innovative approaches against antimicrobial-resistant biofilm infections2019https://doi.org/10.1071/ma19049
N.B. These documents automatically identified may not have been verified by the study sponsor.