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Trial registered on ANZCTR


Registration number
ACTRN12623001119684
Ethics application status
Approved
Date submitted
22/09/2023
Date registered
27/10/2023
Date last updated
27/10/2023
Date data sharing statement initially provided
27/10/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The response of the eye to different ocular allergy eyedrops
Scientific title
Effect and time course of topical ketotifen 0.025% and prednisolone sodium phosphate 0.5% on ocular dendritic cell density, morphology, and topographical distribution in participants with allergic conjunctivitis
Secondary ID [1] 310584 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Seasonal allergic conjunctivitis 331448 0
Perennial allergic conjunctivitis 331449 0
Condition category
Condition code
Eye 328187 328187 0 0
Diseases / disorders of the eye
Inflammatory and Immune System 328399 328399 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1:
In this arm, participants will be given unpreserved unit dose ketotifen 0.025% (250 µg in 1mL) eyedrops. Participants will be instructed to put one drop in each eye for the duration of 14 days.

Arm 2:
In this arm, participants will be given unpreserved prednisolone sodium phosphate 0.5% eyedrops. Participants will be instructed to put one drop in each eye for the duration of 14 days.

Monitor adherence to the intervention:
The Investigator will maintain a participants Medicine Dispensing Log detailing the medication numbers and dates of medication dispensed for each participant during the course of the trial. Unused medications and control eyedrops at the end of the study will be destroyed at the trial site in accordance with local requirements and when site operating procedures permits after the drug accountability has been finalised and signed-off by the Investigator.

Participants will be asked to complete a washout period of 1 week duration before the treatment period for which they will be given topical 0.25% polyethylene glycol 400 eyedrops (lubricant eyedrops) and will be asked to put one drop, twice daily in each eye for 1 week.
Intervention code [1] 326993 0
Treatment: Drugs
Comparator / control treatment
Arm 3:
In this arm, participants will be given unpreserved unit dose 0.4% polyethylene glycol 400 , 0.3% propylene glycol eyedrops (lubricant eyedrops). Participants will be instructed to put one drop in each eye for the duration of 14 days.

Participants will be asked to complete a washout period of 1 week duration before the treatment period for which they will be given topical 0.25% polyethylene glycol 400 eyedrops (lubricant eyedrops) and will be asked to put one drop, twice daily in each eye for 1 week.
Control group
Placebo

Outcomes
Primary outcome [1] 336059 0
The change in dendritic cell density (measured by counting their average number in a given area manually) using in-vivo confocal microscopy.
Timepoint [1] 336059 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Primary outcome [2] 336064 0
The change in dendritic cell density (measured by counting their average number in a given area manually) using in-vivo confocal microscopy.
Timepoint [2] 336064 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [1] 426716 0
The change in dendritic cell morphology (determined by measuring cell body size and presence of dendrites manually), using in-vivo confocal microscopy.
Timepoint [1] 426716 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [2] 426717 0
The change in dendritic cell morphology (determined by measuring cell body size and presence of dendrites manually), using in-vivo confocal microscopy.
Timepoint [2] 426717 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [3] 426718 0
The change in the itchy eye symptom will be assessed usning numerical rating scale (NRS).
Timepoint [3] 426718 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [4] 426719 0
The change in the itchy eye symptom will be assessed usning numerical rating scale (NRS).
Timepoint [4] 426719 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [5] 426721 0
The change in the watery eye symptom will be assessed usning numerical rating scale (NRS).
Timepoint [5] 426721 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [6] 426722 0
The change in the watery eye symptom will be assessed usning numerical rating scale (NRS).
Timepoint [6] 426722 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [7] 427573 0
The change in the burning feeling symptom will be assessed usning numerical rating scale (NRS).
Timepoint [7] 427573 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [8] 427574 0
The change in the burning feeling symptom will be assessed usning numerical rating scale (NRS).
Timepoint [8] 427574 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [9] 427575 0
The change in the foreign body feeling symptom will be assessed usning numerical rating scale (NRS).
Timepoint [9] 427575 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [10] 427576 0
The change in the foreign body feeling symptom will be assessed usning numerical rating scale (NRS).
Timepoint [10] 427576 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [11] 427577 0
The change in the eye redness sign.

This outcome will be assessed by slit lamp examination of the ocular surface. The cornea and contact lens research unit scale (CCLRU) will be used.
Timepoint [11] 427577 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [12] 427578 0
The change in the eye redness sign.

This outcome will be assessed by slit lamp examination of the ocular surface. The cornea and contact lens research unit scale (CCLRU) will be used.
Timepoint [12] 427578 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [13] 427579 0
The change in the conjunctival chemosis sign.

This outcome will be assessed by slit lamp examination of the ocular surface. The Japanese Grading Scale will be used.
Timepoint [13] 427579 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [14] 427580 0
The change in the conjunctival chemosis sign.

This outcome will be assessed by slit lamp examination of the ocular surface. The Japanese Grading Scale will be used.
Timepoint [14] 427580 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [15] 427581 0
The change in the conjunctival papillae sign.

This outcome will be assessed by slit lamp examination of the ocular surface. The Japanese Grading Scale will be used.
Timepoint [15] 427581 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [16] 427582 0
The change in the conjunctival papillae sign.

This outcome will be assessed by slit lamp examination of the ocular surface. The Japanese Grading Scale will be used.
Timepoint [16] 427582 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [17] 427583 0
The change in the conjunctival follicles sign.

This outcome will be assessed by slit lamp examination of the ocular surface. The Japanese Grading Scale will be used.
Timepoint [17] 427583 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [18] 427584 0
The change in the conjunctival follicles sign.

This outcome will be assessed by slit lamp examination of the ocular surface. The Japanese Grading Scale will be used.
Timepoint [18] 427584 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [19] 428198 0
The change in the emotional, physical, and social impact score of the allergic conjunctivitis. The Mini-Rhinoconjunctivitis Quality of Life Questionnaire (Mini-RQLQ) will be used.
Timepoint [19] 428198 0
Pre-treatment (at the baseline visit prior to first dose), 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [20] 428199 0
The change in the emotional, physical, and social impact score of the allergic conjunctivitis. The Mini-Rhinoconjunctivitis Quality of Life Questionnaire (Mini-RQLQ) will be used.
Timepoint [20] 428199 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [21] 428200 0
The change in the severity score of various ocular allergy symptoms. The Aston University Allergy Questionnaire (AUAQ) will be used.
Timepoint [21] 428200 0
Pre-treatment (at the baseline visit prior to first dose), 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [22] 428201 0
The change in the severity score of various ocular allergy symptoms. The Aston University Allergy Questionnaire (AUAQ) will be used.
Timepoint [22] 428201 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [23] 428202 0
The change in the score of the frequency of the ocular allergy symptoms, effects of the symptoms on daily life, actions the patient has undertaken to seek treatment, and satisfaction with these treatments. The Eye Allergy Patient Impact Questionnaire (EAPIQ)
Timepoint [23] 428202 0
Pre-treatment (at the baseline visit prior to first dose), 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [24] 428203 0
The change in the score of the frequency of the ocular allergy symptoms, effects of the symptoms on daily life, actions the patient has undertaken to seek treatment, and satisfaction with these treatments. The Eye Allergy Patient Impact Questionnaire (EAPIQ)
Timepoint [24] 428203 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [25] 428204 0
The dry eye symptoms and the effects it has on vision-related function. The Ocular Surface Disease Index (OSDI) will be used. This questionnaire will only be used at the screening visit to assess the study's inclusion and exclusion criteria.
Timepoint [25] 428204 0
At the screening visit (prior to the participant enrolment).
Secondary outcome [26] 428205 0
The frequency, discomfort and dryness intensity. The Dry Eye Questionnaire (DEQ-5) will be used. This questionnaire will be used at the screening visit only for the assessment of the study inclusion and exclusion criteria.
Timepoint [26] 428205 0
At the screening visit (prior to the participant enrolment).
Secondary outcome [27] 428206 0
The change in the blurriness symptom will be assessed usning numerical rating scale (NRS).
Timepoint [27] 428206 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [28] 428207 0
The change in the blurriness symptom will be assessed usning numerical rating scale (NRS).
Timepoint [28] 428207 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [29] 428208 0
The change in the tiredness symptom will be assessed usning numerical rating scale (NRS).
Timepoint [29] 428208 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [30] 428209 0
The change in the tiredness symptom will be assessed usning numerical rating scale (NRS).
Timepoint [30] 428209 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [31] 428210 0
The change in the sneezing symptom will be assessed usning numerical rating scale (NRS).
Timepoint [31] 428210 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [32] 428211 0
The change in the sneezing symptom will be assessed usning numerical rating scale (NRS).
Timepoint [32] 428211 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).
Secondary outcome [33] 428212 0
The change in the running nose symptom will be assessed usning numerical rating scale (NRS).
Timepoint [33] 428212 0
Pre-treatment (at the baseline visit prior to first dose), 24 hours, 7 days and 14 days post-first dose (during the treatment period).
Secondary outcome [34] 428213 0
The change in the running nose symptom will be assessed usning numerical rating scale (NRS).
Timepoint [34] 428213 0
7 days and 14 days post-treatment completion (after the of end of the treatment period).

Eligibility
Key inclusion criteria
1.Be at least 18 years of age or older.

2. Positive result in the skin prick test.

3. All participants must have current active allergic conjunctivitis symptoms (including itchy eyes or watery eyes or burning feeling or feeling like there is dirt or grit in your eyes) or signs (including redness or conjunctival chemosis or conjunctival papillae or conjunctival follicles), with or without a prior diagnosis of ocular allergy or hay fever.

4. Able to read and comprehend English and give informed consent as demonstrated by signing a record of informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Severe allergic conjunctivitis (reflective from the total symptoms scores of the Mini-RQLQ and OSDI questionnaires) including vernal keratoconjunctivitis and atopic keratoconjunctivitis.

2. Negative result in the skin prick test.

3. Severe asthma.

4. Severe eczema.

5. Past anaphylactic episode.

6. Previous allergic reaction to any component of topical eyedrops used in this study including benzalkonium chloride preservative.

7. Pregnant or breastfeeding/childbirth within three months from the date of recruitment.

8. Regular contact lens wear (wearing contact lenses for at least two or more full days in a week).

9. All other ocular surface diseases except allergic conjunctivitis.

10. Ocular diseases that involve the cornea.

11. Active intraocular inflammation.

12. History of corneal refractive surgery.

13. Systematic conditions affecting the ocular surface include diabetes, thyroid disorder, rheumatoid arthritis and Sjogren's syndrome.

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)
Patients will be given the opportunity to participate in the study following diagnosis of allergic conjunctivitis (Seasonal and Perennial allergic conjunctivitis) in our study.

Eligible participants will be randomly allocated to one of the three study groups in a 1:1:1 ratio based on a pre-determined computer-generated list to ensure every participant has an equal chance of being allocated to any treatment arm. All interventions that will be used in this trial will come in transparent ampules. Originally labelled intervention ampules will be masked by covering the drug information with opaque labels. Intervention ampules will be removed from the original packaging and pre-packed in sealed envelopes, and randomly labelled (intervention A, intervention B, and intervention C). Each envelope will have instructions of use and a sufficient amount of dosage for the treatment period. Each group will be randomly assigned to receive either topical unpreserved ketotifen 0.025% or topical unpreserved prednisolone sodium phosphate 0.5% eyedrops in the treatment group and topical unpreserved 0.4% polyethylene glycol 400, 0.3% propylene glycol eyedrops in the control group. The pre-packing of the eyedrops will be allocated to external personnel (not a member of the investigators' group). The external personnel will be responsible for maintaining the randomisation list.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Eligible participants will be randomised by computer generated list in blocks to either study groups by an independent personnel (not a member of the investigators' 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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
SPSS software (version 28.0; SPSS inc.) will be used. Differences in symptoms and signs between treatment groups and the control group will be assessed using the Independent Sample t-test or Mann-Whitney U test, as appropriate. For dendritic cell density, A linear mixed model with effect for individuals will be used to examine differences in (log) dendritic cell density between groups and between corneal and conjunctival locations. Pairwise comparisons between groups and locations will be obtained within the model. P-values for multiple comparisons between locations will be adjusted by Holm's step-down Bonferroni method.

Mann-Whitney U test (for cell body size) and Fisher’s Exact test (for the presence of dendrites) will be used to assess differences in dendritic cell morphology between groups. Friedman, and Wilcoxon Singed Ranked Test (for cell body size) and Cochran's Q Test (for the presence of dendrites) will be used to assess differences in dendritic cell morphology across locations and the p-values for pairwise comparison between locations were adjusted by Holm's step-down Bonferroni method.

Associations between dendritic cell and ocular surface symptoms and signs will be assessed using a univariate Spearman’s correlation coefficient (for dendritic cell density and cell body size) and Mann-Whitney U test (for the presence of dendrites).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
20/11/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 25523 0
School of Optometry and Vision Science - Kensington
Recruitment postcode(s) [1] 41344 0
2033 - Kensington

Funding & Sponsors
Funding source category [1] 314793 0
University
Name [1] 314793 0
The University of New South Wales - UNSW
Country [1] 314793 0
Australia
Primary sponsor type
University
Name
The University of New South Wales
Address
UNSW Sydney NSW 2052 Australia
Country
Australia
Secondary sponsor category [1] 316795 0
None
Name [1] 316795 0
Address [1] 316795 0
Country [1] 316795 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313805 0
The University of New South Wales Humen Research Ethics Committee C
Ethics committee address [1] 313805 0
Humen Research Ethics Committees (HRECs), UNSW, Sydney, NSW 2052 Australia
Ethics committee country [1] 313805 0
Australia
Date submitted for ethics approval [1] 313805 0
04/10/2023
Approval date [1] 313805 0
16/10/2023
Ethics approval number [1] 313805 0
HC230343

Summary
Brief summary
The prevalence of ocular allergies is increasing worldwide, affecting individuals’ quality of life and causing a significant socioeconomic burden. Allergic conjunctivitis can be managed using a range of treatment options. Ocular inflammatory cell (e.g., dendritic cell) play a substantial role in initiating the immune response in the setting of ocular allergies. The proposed study will be single centre, double-blinded, randomised, placebo-controlled, parallel group clinical trial. All participants will go through a washout period for 1 week using topical 0.25% polyethylene glycol 400 eyedrops (lubricant eyedrops) before starting the trial interventions. This study consists of three arms; arm 1 will be given topical ketotifen 0.025% eyedrops; arm 2 will be given prednisolone sodium phosphate 0.5% eyedrops; the placebo group will be given topical 0.4% polyethylene glycol 400, 0.3% propylene glycol eyedrops. All participants will remain on the trial interventions for 14 days. Assessment of the trial outcomes will take place pre-treatment, 24 hours, 7 days and 14 days after starting the treatment, 7 days and 14 days post-treatment. Both investigators and participants will be double-blinded to the group and treatment allocation until the results have been analysed.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129402 0
Prof Fiona Stapleton
Address 129402 0
School of Optometry and Vision Science, Level 3, North Wing, Rupert Myers Building, Gate 14 Barker Street, UNSW Sydney NSW 2052
Country 129402 0
Australia
Phone 129402 0
+61 293854375
Fax 129402 0
Email 129402 0
[email protected]
Contact person for public queries
Name 129403 0
Fiona Stapleton
Address 129403 0
School of Optometry and Vision Science, Level 3, North Wing, Rupert Myers Building, Gate 14 Barker Street, UNSW Sydney NSW 2052
Country 129403 0
Australia
Phone 129403 0
+61 293854375
Fax 129403 0
Email 129403 0
[email protected]
Contact person for scientific queries
Name 129404 0
Fiona Stapleton
Address 129404 0
School of Optometry and Vision Science, Level 3, North Wing, Rupert Myers Building, Gate 14 Barker Street, UNSW Sydney NSW 2052
Country 129404 0
Australia
Phone 129404 0
+61 293854375
Fax 129404 0
Email 129404 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


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
20348Ethical approval    386586-(Uploaded-26-10-2023-15-22-34)-Study-related document.pdf
20349Study protocol    386586-(Uploaded-22-10-2023-14-38-09)-Study-related document.pdf
20350Informed consent form    386586-(Uploaded-22-10-2023-14-49-46)-Study-related document.pdf



Results publications and other study-related documents

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