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Trial registered on ANZCTR


Registration number
ACTRN12619001121156
Ethics application status
Approved
Date submitted
28/06/2019
Date registered
12/08/2019
Date last updated
27/02/2020
Date data sharing statement initially provided
12/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
2-step versus 1-step sub-retinal injection to assess sub-retinal drug delivery
Scientific title
2-Step versus 1-Step Sub-Retinal Injection to assess the reflux and retention of Actilyse in patients with sub-macular haemorrhage
Secondary ID [1] 298602 0
Nil Known.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sub-macular haemorrhage 313455 0
Condition category
Condition code
Eye 311888 311888 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The overall objective of this study is to assess the reflux and retention of a therapeutic substance (Actilyse) delivered via two different techniques into the sub-retinal space to determine the optimum approach for sub-retinal injections.

Patients diagnosed with sub-macular haemorrhage and identified as suitable for this study will be approached. Only the affected eye will undergo surgery; therefore subjects will be randomised to one or other arm of the study. We will be recruiting from Sydney Eye Hospital.

The surgical procedure will be identical to that undertaken in the routine management of significant sub-macular haemorrhage. The only difference between standard of care in the current study is that sodium fluorescein will be used to track the flow of Actilyse. The surgery takes approximately 30 minutes to complete and the duration is similar in both arms of the study. All study medications will be delivered via a 38g teflon tipped sub-retinal cannula using the viscous fluid control syringe of the Alcon Constellation Vision System.

The surgeon will be either the Principal Investigator (Vitreo-retinal Surgeon and Visiting Medical Officer at Sydney Eye Hospital), or one of the Sub-Investigators (Vitreo-retinal Fellow employed by Sydney Eye Hospital).

Arm 1: A two-step approach, in which a physiologically inert fluid (0.2mL of balanced salt solution) is used to open the potential sub-retinal space, immediately after which Actilyse (50 micrograms) is delivered.

Arm 2: A one-step approach, in which Actilyse (50 micrograms in 0.1mL) itself is used to create a limited iatrogenic retinal detachment, thereby opening up the subretinal space.

In order to compare these two methods, sodium fluorescein (0.01mg in 0.1mL) will be mixed with Actilyse to track its distribution.

Fluid samples will be taken from the eye at the completion of surgery to compare how much fluid has leaked during the surgical procedure. The samples will be taken from the fluid-air exchange, a standard step in vitrectomy surgery. Instead of discarding the fluid extracted, it will be collected instead. The total volume of fluid will be measured, as well as the concentration of fluorescein in this solution, using a fluorophotometer. Once measurements are taken, the fluid will be destroyed.

The procedure will be video-recorded in order to provide a means of subjectively assessing reflux at the time of injection of the Actilyse.

Participants will be assessed with respect to safety outcomes for which standardised procedure have been developed. Standard of care post-surgery visits will be conducted as per normal through the Outpatient Department, Sydney Eye Hospital. There will be no additional study-specific visits post-surgery.
Intervention code [1] 314865 0
Treatment: Surgery
Comparator / control treatment
The control group are those participants who will receive the 1-step injection.
The experimental group are those participants who will receive the 2-step injection.
Control group
Active

Outcomes
Primary outcome [1] 320559 0
The primary outcome is the amount of refluxed sodium fluorescein between the two-step and one-step approach. This will be measured using fluorophotometry.
Timepoint [1] 320559 0
Review of results after the enrollment and surgeries of the first 10 subjects. The primary endpoint is the amount of refluxed drug immediately following treatment: if one technique is clearly superior to the other at the halfway mark, the trial will be terminated early.
Secondary outcome [1] 372002 0
Time taken to perform the sub-retinal injection. This is measured using video footage and cross-correlated with information stored on the constellation device.
Timepoint [1] 372002 0
Assessed during surgical procedure.

Eligibility
Key inclusion criteria
• Participants will be patients with either a new or an established diagnosis of age-related macular degeneration and with a 7 day or less history of vision loss secondary to sub-macular haemorrhage.
• Age greater than or equal to 18 years (Participants with sub-macular haemorrhage or retinal arteriolar macroaneurysm are typically over 60 years of age.)
• Area of haemorrhage of greater than 1 disc area but not meeting the criteria for massive sub-retinal haemorrhage (haemorrhage extending beyond the temporal vascular arcades).
• Density of haemorrhage sufficient to obscure the RPE and choroidal detail.
• Haemorrhage involving the fovea.
• BCVA equal to, or worse than 6/60
• Written informed consent has been obtained
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Symptoms suggestive of sub-macular haemorrhage for > 7 days.
• Amblyopia in the study eye.
• Presence of another ocular disease affecting vision in the study eye.
• Known allergy to fluorescein
• Women who are pregnant, nursing or planning pregnancy or who are of childbearing potential and not using reliable means of contraception. (A woman is considered of childbearing potential unless she is post-menopausal and without menses for 12 months or is surgically sterilised)
• Participants unable to adhere to post-operative posturing.
• BCVA < HM
• Known allergy to agents used in the study e.g. fluorescein sodium
• Known history of significant cardio-pulmonary disease
• Multiple concomitant drug therapies – in particular, beta-blockers (including eye drops)
• Patients who, in the opinion of the treating surgeon and anaesthetist, are unfit for a surgical procedure, with a condition that may put the patient at considerable risk, may confound the study results or may interfere significantly with the patient’s participation in the study.

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)
Methods used to generate the sequence in which subjects will be randomised (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
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/09/2019
Actual
11/11/2019
Date of last participant enrolment
Anticipated
31/12/2020
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 14104 0
Sydney Hospital and Sydney Eye Hospital - Sydney
Recruitment postcode(s) [1] 26897 0
2000 - Sydney

Funding & Sponsors
Funding source category [1] 303144 0
Charities/Societies/Foundations
Name [1] 303144 0
Foundation Fighting Blindness
Country [1] 303144 0
United States of America
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney, Camperdown NSW 2006
Country
Australia
Secondary sponsor category [1] 303141 0
None
Name [1] 303141 0
Address [1] 303141 0
Country [1] 303141 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303693 0
South Eastern Sydney Local Health District HREC - Prince of Wales Hospital
Ethics committee address [1] 303693 0
Ethics committee country [1] 303693 0
Australia
Date submitted for ethics approval [1] 303693 0
Approval date [1] 303693 0
30/01/2019
Ethics approval number [1] 303693 0

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

Contacts
Principal investigator
Name 94514 0
A/Prof Matthew Simunovic
Address 94514 0
Retinal Unit
Sydney Eye Hospital
8 Macquarie Street
Sydney NSW 2000
Country 94514 0
Australia
Phone 94514 0
+61 2 93827111
Fax 94514 0
Email 94514 0
[email protected]
Contact person for public queries
Name 94515 0
Stella Xu
Address 94515 0
Save Sight Institute
University of Sydney
8 Macquarie St.
Sydney NSW 2000
Country 94515 0
Australia
Phone 94515 0
+61293827111
Fax 94515 0
Email 94515 0
[email protected]
Contact person for scientific queries
Name 94516 0
Matthew Simunovic
Address 94516 0
Retinal Unit
Sydney Eye Hospital
8 Macquarie Street
Sydney NSW 2000
Country 94516 0
Australia
Phone 94516 0
+61293827111
Fax 94516 0
Email 94516 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
Sharing of IPD is not covered in the Ethics/Governance agreement for this clinical trial.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2536Ethical approval    377864-(Uploaded-26-06-2019-17-56-36)-Study-related document.pdf
2541Study protocol    377864-(Uploaded-26-06-2019-17-57-17)-Study-related document.pdf
2542Informed consent form    377864-(Uploaded-26-06-2019-17-57-40)-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
EmbaseTwo-step versus 1-step subretinal injection to compare subretinal drug delivery: A randomised study protocol.2021https://dx.doi.org/10.1136/bmjopen-2021-049976
EmbaseSodium Fluorescein as an Optical Label to Evaluate Subretinal Injection.2023https://dx.doi.org/10.1097/IAE.0000000000002800
N.B. These documents automatically identified may not have been verified by the study sponsor.