Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000302954
Ethics application status
Approved
Date submitted
15/03/2011
Date registered
22/03/2011
Date last updated
22/03/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
Branch Retinal Vein Occlusion Treatment Trial
Scientific title
A 12 month, phase 3, single-centre, randomised trial to compare the the safety and efficacy of a 125mg/0.05ml Bevacizumab intravitreal injection to macular grid laser therapy in the treatment of macular edema following Branch Vein Retinal Occlusion (BRVO) .
Secondary ID [1] 259705 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Branch Vein Retinal Occlusion 261279 0
Condition category
Condition code
Eye 259428 259428 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Bevacizumab is a recombinant humanised monoclonal antibody to vascular epithelial growth factor (VEGF) designed for IV administration and approved for treatment of colorectal cancer.
It has recently emerged as a novel therapeutic strategy for retinal diseases, especially age-related macular degeneration, and, in retrospective short-term studies, has also proven to be effective in central retinal and branch retinal vein occlusion. None of the clinical and experimental studies published so far have found any drug-related toxic effects on any retinal structures.
Patients will receive a minimum of 3 doses of Bevacizumab 1.25 mg via intravitreal injection to the eye at monthly intervals, then as required for up to 12 months.The procedure on each occasion will take 5 minutes.
Intervention code [1] 264217 0
Treatment: Drugs
Comparator / control treatment
The other group will receive macular grid laser.
Type of Laser is Alcon Ophthalas 532 with 100 micrometre spot size, 80-150MW power,0.1 second duration. The duration of the treatment is less than 5 minutes.
Control group
Active

Outcomes
Primary outcome [1] 262327 0
Primary outcome measure - Best Corrected Visual Accuity log MAR
BCVA will be measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) method. BCVA will be measured in both eyes at the baseline visit and at each follow up visit
Timepoint [1] 262327 0
Baseline then monthly for 12 months
Secondary outcome [1] 273546 0
1 Central retinal thickness
This will be measured by Optical Coherence Tomography (OCT): OCT is a laser-based, non-invasive, diagnostic system providing high-resolution images of the retina. OCT will be performed in both eyes at baseline and at every follow up visit.
Timepoint [1] 273546 0
Baseline then monthly for 12 months
Secondary outcome [2] 273547 0
2 Neovascular complication
Fundus photography: will be performed in both eyes when a Fluorescein Angiography is required.
Fundus Fluorescein Angiography (FFA): FFA will be conducted in both eyes to provide angiographic evidence of leakage involving the perifoveal capillary network at baseline and evidence of change over time. Analysis of Fluorescein leakage, capillary non-perfusion and cystoid changes.
Timepoint [2] 273547 0
Baseline then monthly for 12 months
Secondary outcome [3] 273548 0
3 Drug related adverse effects
Measured by history taking and observation of medical staff
There is a theoretical increased risk of strokes with anti-VEGF, however the actual risk of stroke with anti-VEGF is unknown
Timepoint [3] 273548 0
Baseline then monthly for 12 months
Secondary outcome [4] 273549 0
4 Complications related to intravitreal injection
Measured by history taking and observation of medical staff
Endophthalmitis (infection of the eye): symptoms include burning sensation, eye pain, increased blurring of vision, light sensitivity and redness. Studies have shown that the chance of getting an infection is 0.1 per cent and this is why antibiotics are given prior and following treatment.
Elevated Eye Pressure: this is usually temporary and due to an increase of fluid entering the eye.
Retinal Detachment, Bleeding and Cataract Formation: these are unusual complications occurring in less than 1 per cent of patients in trial studies.
Other side effects not related the eye include high blood pressure, nose and throat infection and headache.
Timepoint [4] 273549 0
Baseline then monthly for 12 months

Eligibility
Key inclusion criteria
> 18 years of age
Males and females
Duration of BRVO > 3 months
Best Correct Visual Acuity (BCVA) < 20/40
CRT > 250 micro m in the central subfield or >300microns in the inner subfield.
Adequate renal function (glomerular filtration calculated by Cockcroft/Gault formula or measure urine creatinine clearance > or = to 50 mL/minute)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
History of submacular surgery or other surgical intervention for Aged Macular Degeneration (AMD) in the study eye, glaucoma filtration surgery, corneal transplant surgery or diabetic maculopathy.
Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within one month preceding baseline,
Extracapsular extraction of cataract with phacoemulsification within three months preceding Baseline, or a history of post-operative complications within the last 12 months preceding Baseline in the study eye (uveitis, cyclitis, etc.),
History of uncontrolled glaucoma in the study eye (defined as intraocular pressure is greater than or equal to 25 mmHg despite treatment with anti-glaucoma medication),
Aphakia with absence of the posterior capsule in the study eye,
Active intraocular inflammation (grade trace or above) in the study eye,
Any active infection involving ocular adnexa including infectious conjunctivitis, keratitis, scleritis, endophthalmitis, as well as idiopathic or autoimmune-associated uveitis in either eye,
Vitreous hemorrhage or history of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye,
Presence of a retinal pigment epithelial tear involving the macula in the study eye, Subfoveal fibrosis or significant atrophy in the study eye
Women of childbearing potential not using the contraception method(s) specified in this study (specify), as well as women who are breastfeeding
Known sensitivity to study drug(s) or class of study drug(s)
Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study (specify as required)
Use of any other investigational agent in the last 30 days

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)
Branch retinal vein occlusion with associated macular oedema of any aetiology will be recruited for the study.
At the baseline visit a medical history, anterior and posterior segment examination, best corrected visual acuity by log MAR charts, central retinal thickness by OCT and fundus fluorescein angiography will be performed.
Patients will be followed up for 3 months at 4 weekly intervals recording BCVA and CRT by OCT.

Patients who have BCVA < 20/40 and CRT > 250 micro m in the central subfield or >300microns in the inner subfields at three months, will be recruited for the trial. Patients will be randomised at three months to either the macular laser group or the Bevacizumab injection group.

The group assigned for the macular grid laser treatment as per Branch Vein Occlusion Study (BVOS) criteria. BRVO involving foveal centre with perfused macula, recent onset 3- 18 months, no diabetic retinopathy, BCVA <20/40).

The second group will be assigned for three injections of intravitreal Bevacizumab 1.25 mg 4 weekly intervals.
At 6 months further need of laser or Bevacizumab will be decided by the investigators on set criteria.(CRT worsening >50micro m, CRT >250 micro m or inner subfield >300 micro m, visual acuity drop > 5 letters log MAR) Patients will be followed up at 4 weekly intervals for a total of 12 months.
Patients will be assigned randomly in sequential order using opaque numbered envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomisation table created by computer software (i.e., computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
17/12/2008
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
22
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 264663 0
Hospital
Name [1] 264663 0
Royal Adelaide Hospital
Country [1] 264663 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Ophthalmology Network
Level 8, East Wing
North Terrrace
Adelaide
SA 5000
Country
Australia
Secondary sponsor category [1] 263801 0
None
Name [1] 263801 0
Address [1] 263801 0
Country [1] 263801 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 266660 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 266660 0
Ethics committee country [1] 266660 0
Australia
Date submitted for ethics approval [1] 266660 0
01/10/2008
Approval date [1] 266660 0
11/11/2008
Ethics approval number [1] 266660 0
081022

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

Contacts
Principal investigator
Name 32290 0
Address 32290 0
Country 32290 0
Phone 32290 0
Fax 32290 0
Email 32290 0
Contact person for public queries
Name 15537 0
Associate Professor Robert Casson MBBS Dphil FRANZCO
Address 15537 0
Director of Ophthalmic Research
Royal Adelaide Hospital
East Wing, Level 8
Adelaide
SA 5000
Country 15537 0
Australia
Phone 15537 0
+61 8 8222 2732
Fax 15537 0
+61 8 8222 2741
Email 15537 0
[email protected]
Contact person for scientific queries
Name 6465 0
Associate Professor Robert Casson MBBS Dphil FRANZCO
Address 6465 0
Director of Ophthalmic Research
Royal Adelaide Hospital
East Wing, Level 8
Adelaide
SA 5000
Country 6465 0
Australia
Phone 6465 0
+61 8 8222 2732
Fax 6465 0
+61 8 8222 2741
Email 6465 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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