Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000185561
Ethics application status
Approved
Date submitted
19/01/2015
Date registered
25/02/2015
Date last updated
22/04/2020
Date data sharing statement initially provided
23/01/2019
Date results information initially provided
22/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Tenecteplase in the acute management of branch retinal vein occlusion.
Scientific title
The effect of Tenecteplase on intravenous thrombus and retinal blood flow in patients with branch retinal vein occlusion (BRVO).
Secondary ID [1] 285961 0
Nil
Universal Trial Number (UTN)
U1111-1166-0325
Trial acronym
T-BRVO study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Branch retinal vein occlusion. 293894 0
Condition category
Condition code
Eye 294197 294197 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients with a branch retinal vein occlusion (BRVO) less than 3 weeks will receive one intraocular injection of 100 micrograms Tenecteplase or sham injection. The procedure will be performed by the study investigator and will follow the Royal Australian and New Zealand College guidelines for intraocular injection. For the sham injection procedure, an empty syringe hub will be placed against the eye. The randomisation will be 1:1. Forty patients will be recruited to the study. Optical Coherence Tomography (OCT) will be used to measure centre point foveal thickness in the macula and to estimate the volume of the intraluminal clot. Fluorescein angiography (FA) will measure retinal flow over the blockage. Retinal blood flowmetry will measure retinal blood flow in the area of the BRVO. Best corrected vision will be measured using an ETDRS Lighthouse 4 meter chart. Optical Coherence Tomography Angiography (OCTA) will be used to examine changes to the radial peripapillary capillaries and the deep capillary networks. At the Day 7 visit, anti-VEGF treatment will start.
Intervention code [1] 290937 0
Treatment: Drugs
Comparator / control treatment
The sham injection procedure consists of an empty syringe hub been placed against the eye. It simulates the actual injection procedure and is routinely used in clinical trials using a sham intraocular injection procedure. All participants will start anti-VEGF treatment at Day 7.
Control group
Placebo

Outcomes
Primary outcome [1] 293986 0
Presence of intravenous thrombus assessed by OCT.
Timepoint [1] 293986 0
7 Days post injection.
Primary outcome [2] 294141 0
Venous outflow in the affected vein assessed using fluorescein angiography and flowmetry.
Timepoint [2] 294141 0
7 Days post injection.
Secondary outcome [1] 312289 0
Visual acuity assessed using an ETDRS Lighthouse 4m chart.
Timepoint [1] 312289 0
One month post injection.
Secondary outcome [2] 312290 0
To evaluate the incidence of the clot reforming using OCT.
Timepoint [2] 312290 0
One month post injection.
Secondary outcome [3] 312291 0
To measure macular centre point thickness using OCT.
Timepoint [3] 312291 0
One month post injection.
Secondary outcome [4] 312292 0
To evaluate venous outflow in the affected vein using fluorescein angiography and flowmetry.
Timepoint [4] 312292 0
One month post injection.
Secondary outcome [5] 332911 0
To determine both the nature and sequence of changes to the radial peripapillary capillaries and the deep capillary networks as a composite secondary outcome using optical coherence tomography angiography (OCTA).
Timepoint [5] 332911 0
One and Three months post injection.

Eligibility
Key inclusion criteria
1. Foveal centre involved macular oedema secondary to BRVO less than 3 weeks in duration.
2. Major supero-temperal or infero-temperal BRVO.
3. Mean central foveal thickness greater or equal to 250 microns on spectral domain OCT.
4. Adults greater or equal to 18 years.
5. Best corrected visual acuity 20/40 to 20/320 (73-24 letters on ETDRS chart).
6. Clear ocular media and adequate pupillary dilation.
7. Intraocular pressure equal or less than 25mmHg.
8. Written informed consent.
9. No other significant ocular pathology.
10. Willing, committed and able to return for all clinic visits and complete all study related procedures.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Any previous treatment for BRVO.
2. Brisk afferent pupillary defect.
3. Evidence on examination of any diabetic retinopathy.
4. Women of child bearing potential not using contraception, as well as women who are breastfeeding.
5. Known sensitivity to study drug or class of study drug.
6. Use of any other investigational agent in the last 30 days.
7. Any other ocular condition in the study eye that would prevent improvement in visual acuity, e.g.macular ischaemia, underlying macular degeneration, epi-retinal membrane.
8. Neovascularisation of the iris, dics or retina.
9. Previous treatment with intravitreal corticosteroids, intravitreal anti-VEGF agents or macular grid laser in the previous 3 months.
10. Aphakia or presence of anterior chamber lens in the study eye.
11. Significant media opacities such as cataract.
12. Previous pars plana vitrectomy.
13. History of retinal detachment or surgery for retinal detachment.
14. Any condition which would preclude a patient's ability to comply with the study requirements or to be available for the duration of the study.
15. Any active infection involving ocular adnexa including infectious conjunctivitis, keratitis, sclertitis, endophthalmitis as well as idiopathic or autoimmune-associated uveitis in either eye.
16. Extra capsular extraction of cataract with phacoemulsification within 3 months preceding baseline, or a history of post-operative complications within 12 months preceding baseline in the study eye (uveitis, cyclitis etc.).
17. Contra indication to pupil dilation in either eye.
18. Allergy to fluorescein.

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 presenting to ophthalmic clinics at Lions Eye Institute and the Ophthalmology Department at Royal Perth Hospital with a branch retinal vein occlusion less the 3 weeks in duration will be asked if they would like to participate in the study. The Investigator will discuss all treatment options with the patient. If the patient is interested in participating in the study, the investigator will give the patient a copy of the Participant Information and Consent Form to read and discuss with their family, friends and GP. The baseline visit will take place at Lions Eye Instutite. The participant will sign the consent form prior to performing any study procedures. The participant's vision will be checked (best corrected visual acuity (BCVA)), the eye will be examined and there will be a number of photographic procedures performed (OCT, colour photography, fluorescein angiography, OCTA and flowmetry) to determine eligibilty for the study. If the participant is eligible, they will be randomly assigned to the study treatment (100 micrograms Tenecteplase) or the sham treatment. The randomisation will be 1:1 using central computer randomisation as the allocation of concealment The injection procedure (treatment and sham) will take place at Royal Perth Hospital.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The treatment assignments are compiled using a list of computer generated pseudo-random numbers in permuted blocks of variable size. Patients are randomised for treatment in one eye only
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
1. Patient demographic and baseline characteristics will be summarised for all participants to describe the study population and evaluate treatment group comparability. Continuous variables will be summarised by descriptive statitistics and categorical variables will be summarised by frequency distribution.
2. The primary outcome will be the improvement in retinal blood flow at the site of the occlusion between the two groups at the primary endpoint 7 days. ANOVA will be used to determine whether there is a statistical difference between the treatment groups at the various time points.
3. The secondary outcome regarding efficacy will be the percentage change in visual acuity and macular thickness measured by OCT at 7 days (primary end point) and 30 days (follow up time point). The measurement at these points will be compared with baseline to evaluate the final improvement in addition to the investigation trend.
4. Logistic regression can be used for further explorative analysis of binary endpoints which will be considered during the data analysis stage depending on the nature of the data.
5. This study will use 20 participants for each group, this is based on the consideration of power of 0.80 and the alpha of 0.05.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/07/2015
Actual
15/01/2016
Date of last participant enrolment
Anticipated
31/12/2020
Actual
5/10/2017
Date of last data collection
Anticipated
1/03/2021
Actual
22/11/2017
Sample size
Target
40
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 3323 0
Lions Eye Institute Day Surgery Centre - Nedlands
Recruitment hospital [2] 3324 0
Royal Perth Hospital - Perth

Funding & Sponsors
Funding source category [1] 290544 0
Other Collaborative groups
Name [1] 290544 0
The Ophthalmic Research Institute of Australia (ORIA).
Country [1] 290544 0
Australia
Primary sponsor type
Other
Name
Lions Eye Institute
Address
2 Verdun St
Nedlands
WA
6009
Country
Australia
Secondary sponsor category [1] 289236 0
None
Name [1] 289236 0
Address [1] 289236 0
Country [1] 289236 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292192 0
Royal Perth Hospital Human Research Ethics Committee
Ethics committee address [1] 292192 0
Ethics Office
Level 5, Colonial House
Royal Perth Hospital
Murray St
Perth
6000
WA
Ethics committee country [1] 292192 0
Australia
Date submitted for ethics approval [1] 292192 0
03/02/2015
Approval date [1] 292192 0
02/04/2015
Ethics approval number [1] 292192 0
REG14-149

Summary
Brief summary
The primary aim of this study is to show that an injection of 100 micrograms of Tenecteplase (TNK) into the back of the eye will dissolve the clot and restore venous outflow within a week in patients who have recently suffered a branch retinal vein occlusion (BRVO) (clot in a branch of the retinal vein). Laser treatment has been the standard treatment for BRVO, and is now superseded by injecting anti-VEGF antibodies into the back of the eye. The visual outcome in patients treated this way has improved, but vision does not always return and ongoing injections are often required. Attempts at breaking the clot have been tried using tissue plasminogen activator (tPA), but they have not been effective. TNK is a third generation thrombolytic developed to address some of the short comings of tPA. Our research has shown that TNK is less toxic than tPA, it has a shorter clot contact time to be effective and it is able to penetrate the retina. We have used TNK to treat sub-retinal macula haemorrhage in humans without any problems. In this study, forty patients with a BRVO of less than 3 weeks will be enrolled with a 1:1 randomisation to the TNK treatment (100 micrograms) or sham treatment. Patients will be recruited from the retinal clinics at Royal Perth Hospital and the Lions Eye Institute. At the Baseline visit, consent will be obtained before any study procedure occurs. The study procedures are: best corrected visual acuity examination, ophthalmic examination (eye examination), photography (includes fluorescein angiography, colour photos and optical coherence tomography (OCT)), optical coherence tomography angiography (OCTA) and flowmetry. If eligible, the study participant will be randomised and treated at Day 0. The study procedures outlined above will be repeated at Day 2, Day 7,Day 30 and Day 90. All participants will start anti-VEGF treatment at Day 7; the current standard treatment. The Day 30 examination will determine if there is evidence of the clot reforming. We aim to show the resolution of the clot and improved retinal blood flow over the area of the blocked vein within a week of the TNK injection using the data from the fluorescein angiography, OCT and flowmetry. If the results are promising, then an application for NH&MRC funding for a multicentre study will be sought.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 53998 0
Prof Ian McAllister
Address 53998 0
Lions Eye Institute
2 Verdun St
Nedlands
6009
WA
Country 53998 0
Australia
Phone 53998 0
+61 8 9381 0870
Fax 53998 0
+61 8 9381 0766
Email 53998 0
[email protected]
Contact person for public queries
Name 53999 0
Prof Ian McAllister
Address 53999 0
Lions Eye Institute
2 Verdun St
Nedlands
6009
WA
Country 53999 0
Australia
Phone 53999 0
+61 8 9381 0870
Fax 53999 0
+61 8 9381 0766
Email 53999 0
[email protected]
Contact person for scientific queries
Name 54000 0
Prof Ian McAllister
Address 54000 0
Lions Eye Institute
2 Verdun St
Nedlands
6009
WA
Country 54000 0
Australia
Phone 54000 0
+61 8 9381 9870
Fax 54000 0
+61 8 9381 0766
Email 54000 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
All participant data is de-identified and not linked to the participant.
Ethics approval did not include the release of individual participant data.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
6725Study protocol  [email protected]
6726Informed consent form  [email protected]
6727Ethical approval  [email protected]



Results publications and other study-related documents

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Documents added automatically
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