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Trial registered on ANZCTR


Registration number
ACTRN12620001230943p
Ethics application status
Not yet submitted
Date submitted
12/10/2020
Date registered
17/11/2020
Date last updated
17/11/2020
Date data sharing statement initially provided
17/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of the effect of Carbonic Anhydrase inhibitor eye drops on vision outcomes in patients receiving macular hole repair surgery
Scientific title
A study of the effect of Carbonic Anhdrase inhibitor eye drops on vision outcomes in patients receiving macular hole repair surgery
Secondary ID [1] 302510 0
RD020106 Waikato district health board approval of research
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Macular Hole 319373 0
Condition category
Condition code
Eye 317345 317345 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised controlled trial looking at eyes that have residual subretinal fluid with hole closure after macular hole repair surgery
1 arm of the study will have standard of care treatment to macular hole eyes after repair surgery and the other arm will receive additional Brinzolamide drops postoperatively. Brinzolamide tartrate 0.2% eye drops will be used to the operated eye twice a day, from 2 weeks out from macular hole repair surgery until the subretinal fluid at the macula has cleared fully or until 1 year out from the surgery, whichever is the earliest.
One drop of the drug is the standard dose. Each participant will be asked at each visit if they've missed any doses.
Intervention code [1] 318803 0
Treatment: Drugs
Comparator / control treatment
Control group has active treatment with standard care eye drops which include steroid drops for 6 weeks and antibiotic drops for 1 week.
The steroid drop used will be prednisolone actetate 1% 1 drop dose 4 x a day
The antibiotic drop used will be chloramphenicol 1 drop dose 4 x a day
Control group
Active

Outcomes
Primary outcome [1] 325386 0
Change in LogMAR vision in operated eye.
Timepoint [1] 325386 0
1 year after surgery
Primary outcome [2] 325387 0
Proportion of eyes with total resolution of subretinal fluid assessed by Optical Coherence Tomography scanning
Timepoint [2] 325387 0
1 year after surgery
Secondary outcome [1] 387728 0
LogMAR visual acuity postoperatively
Timepoint [1] 387728 0
6 weeks, 3 months, 6 months 9 months out from surgery
Secondary outcome [2] 387729 0
Proportion of eyes with total resolution of subretinal fluid assessed by Optical Coherence Tomography scanning
Timepoint [2] 387729 0
Measured at 6 weeks, 3 months, 6 months, 9 months after surgery
Secondary outcome [3] 387730 0
Volume of fluid under macula.
This will be estimated by measuring (a)the average radius (r) of subfoveal fluid on OCT scanning and (b) the height (h) of the subfoveal fluid on OCT scanning. Using the formula 3.14 x r squared x h/3, the volume can be estimated.
Timepoint [3] 387730 0
6 weeks, 3 months,6 months, 9 months after surgery
Secondary outcome [4] 387731 0
Adverse effects of eye drops such as red eye, watering and irritation. There could be skin irritation if severe. A bitter or sour taste in the mouth is occasionally reported.
Patients would be encouraged to report to the principal investigator if symptoms occurred. Patients will be asked at each visit if the drops are being tolerated
Timepoint [4] 387731 0
At any time point in the first year after the surgery

Eligibility
Key inclusion criteria
Patients with macular hole repair and residual submacular fluid at the 2 week postoperative timepoint
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Allergy to carbonic anhydrase inhibitors
Underlying macular pathology other than macular hole ie age related macular degeneration or diabetic maculopathy or vein occlusion
Traumatic macular holes

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 is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Figures used from Pioneer study data
"Factors associated with persistent subfoveal fluid and complete macular hole closure in the PIONEER study" by Ehlers et al in Invest Ophthalmol Vis Sci 2015;56:1141-1146

Assuming at 1 month after surgery that the Brinzolamide intervention will reduce the subfoveal fluid by 50% compared with the control group, the number of eyes needed to be treated is 44 in each arm if randomised 1 to 1 , brinzolamide to standard of care.

This uses a type 1 error of 0.05 and type 2 error of 0.2 using a difference of means of 2791 micron squared area of subfoveal fluid involvement on OCT scanning and a SD of 5827 (figures from PIONEER)

The primary outcome is proportion with resolution of fluid, but these figures for area of subfoveal fluid are a good proxy in the absence of any useful other data

Recruitment
Recruitment status
Not yet recruiting
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 outside Australia
Country [1] 23054 0
New Zealand
State/province [1] 23054 0
Waikato

Funding & Sponsors
Funding source category [1] 306945 0
Hospital
Name [1] 306945 0
Waikato Hospital
Address [1] 306945 0
183 Pembroke Street, Hamilton 3204
Country [1] 306945 0
New Zealand
Funding source category [2] 307193 0
Hospital
Name [2] 307193 0
Bridgewater Day Surgery
Address [2] 307193 0
130 Grantham Street
Hamilton 3204
Country [2] 307193 0
New Zealand
Primary sponsor type
Individual
Name
Stephen Guest
Address
Waikato Hospital Eye Clinic,
183 Pembroke St
Hamilton 3204
NZ
Country
New Zealand
Secondary sponsor category [1] 307504 0
Individual
Name [1] 307504 0
Thiyagaraj Krishnan
Address [1] 307504 0
Waikato Hospital Eye Clinic,
183 Pembroke St
Hamilton 3204
NZ
Country [1] 307504 0
New Zealand

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 307086 0
Health and Disability Ethics Committee
Ethics committee address [1] 307086 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 307086 0
New Zealand
Date submitted for ethics approval [1] 307086 0
07/12/2020
Approval date [1] 307086 0
Ethics approval number [1] 307086 0

Summary
Brief summary
The study is looking to see if adding an extra eye drop (Brinzolamide) to the normal eye drops (Prednisolone acetate and Chloramphenicol) patients receive after macular hole repair operation, will improve their vision in the long term. Most people after macular hole surgery have some fluid underneath the macula that hangs around for many months even though the hole has closed. Fluid in this position prevents the sight from improving as quickly as we’d like and we believe the extra eye drop we’re trying may make the fluid go away faster. This may make sight better long term than it would be if we just used the normal eye drops. This drop has been used in other forms of macular disease to improve fluid resolution with success.

The extra drop we’re trying in this study is already used by many thousands of New Zealanders with glaucoma and is known to be very safe. However, as with all eye drops there is a very small chance that patients may experience side effects. We will be randomising patients with fluid underneath the macula post-surgery to either receive the extra drop or just the standard drop regime via computer assisted randomisation. Patients may be required to attend one additional clinic appointment to determine the efficacy of the treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105982 0
Mr Thiyagaraj Krishnan
Address 105982 0
Waikato Hospital Eye Clinic,
183 Pembroke St
Hamilton 3204
NZ
Country 105982 0
New Zealand
Phone 105982 0
+64211465897
Fax 105982 0
Email 105982 0
thiyagaraj@hotmail.com
Contact person for public queries
Name 105983 0
Mr Stephen Guest
Address 105983 0
Waikato Hospital Eye Clinic,
183 Pembroke St
Hamilton 3204
NZ
Country 105983 0
New Zealand
Phone 105983 0
+64272010307
Fax 105983 0
Email 105983 0
stephen.guest@waikatodhb.health.nz
Contact person for scientific queries
Name 105984 0
Mr Stephen Guest
Address 105984 0
Waikato Hospital Eye Clinic,
183 Pembroke St
Hamilton 3204
NZ
Country 105984 0
New Zealand
Phone 105984 0
+64272010307
Fax 105984 0
Email 105984 0
stephen.guest@waikatodhb.health.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual participant data collected during the trial, after de-identification
When will data be available (start and end dates)?
Immediately after publication and no end date
Available to whom?
Anyone who wishes to access it
Available for what types of analyses?
Any purpose
How or where can data be obtained?
Via principal investigator Thiyagaraj Krishnan with email:
thiyagaraj@hotmail.com
What supporting documents are/will be available?
No other documents available
Summary results
No Results