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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01599650




Registration number
NCT01599650
Ethics application status
Date submitted
2/05/2012
Date registered
16/05/2012
Date last updated
10/11/2016

Titles & IDs
Public title
Efficacy and Safety of Ranibizumab With or Without Laser in Comparison to Laser in Branch Retinal Vein Occlusion
Scientific title
A 24-month, Phase IIIb, Open-label, Randomized, Active Controlled, 3-arm, Multicenter Study Assessing the Efficacy and Safety of an Individualized, Stabilization-criteria-driven PRN Dosing Regimen With 0.5-mg Ranibizumab Intravitreal Injections Applied as Monotherapy or With Adjunctive Laser Photocoagulation in Comparison to Laser Photocoagulation in Patients With Visual Impairment Due to Macular Edema Secondary to Branch Retinal Vein Occlusion
Secondary ID [1] 0 0
2011-002859-34
Secondary ID [2] 0 0
CRFB002E2402
Universal Trial Number (UTN)
Trial acronym
BRIGHTER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Branch Retinal Vein Occlusion 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ranibizumab
Treatment: Surgery - Laser

Experimental: 1-ranibizumab monotherapy - Ranibizumab 0.5 mg

Experimental: 2-ranibizumab with laser - Ranibizumab 0.5 mg + laser

Active Comparator: 3-laser monotherapy - Laser monotherapy with Ranibizumab 0.5 mg from Month 6


Treatment: Drugs: Ranibizumab


Treatment: Surgery: Laser
laser photocoagulation

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change in Visual Acuity: BCVA Change at Month 6 Compared to Baseline in Patients With Visual Impairment Due to Branch Retinal Vein Occlusion (BRVO) - Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)
-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 6 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and assessed by an ANOVA model.
Timepoint [1] 0 0
Baseline, 6 Months
Secondary outcome [1] 0 0
The Mean Average Change in Visual Acuity From Month 1 Through Month 24 Compared to Baseline - Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. (A positive average change from baseline of BCVA indicates improvement): Mean Average Change: for each patient, first average change is calculated as the average of the changes from baseline to Month 1 over Month 24. Then, mean average change is calculated as the average of average changes across all patients.
Timepoint [1] 0 0
Baseline, 24 Months
Secondary outcome [2] 0 0
Number of Ranibizumab Treatments From Day 1 to Month 23 by Treatment Group - Number of injections provided to the patients during the 23 month period and conducted within FAS with LOCF and observed data.
Timepoint [2] 0 0
Day 1 through Month 23
Secondary outcome [3] 0 0
Mean Average Change in Visual Acuity (BCVA Letters) From Month 1 Through Month 6 - Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters.(A positive average change from baseline of BCVA indicates improvement): Mean Average Change: for each patient, first average change is calculated as the average of the changes from baseline to Month 1 over Month 6. Then, mean average change is calculated as the average of average changes across all patients.
Timepoint [3] 0 0
From Baseline through Month 6
Secondary outcome [4] 0 0
The Mean Change in Visual Acuity BCVA (Letters) From Baseline at Month 12 and Month 24 - Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 12 and Month 24 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and were assessed by an ANOVA model.
Timepoint [4] 0 0
Baseline, Month 12 and Month 24
Secondary outcome [5] 0 0
The Percent of Patients With a Visual Acuity Gain of =1, =5, =10, =15, and =30 Letters From Baseline up to Month 6 and Month 24, by Visit - BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An increased score indicates improvement in acuity. This outcome assessed the number of participants who had improvement of =1, =5, =10, =15, and =30 letters of visual acuity at Month 6 & Month 24 as compared with baseline, was assessed by an ANOVA model. Endpoints related to the proportion of patients with BCVA letter gain or loss from Baseline was analyzed via stratified Cochran-Mantel-Haenszel test with stratification based on baseline BCVA (baseline BCVA less than or equal to 39, 40 to 59, greater than or equal to 60 letters, treatment groups).
Timepoint [5] 0 0
Baseline, Month 6 and Month 24
Secondary outcome [6] 0 0
Number of Patients With a BCVA Improvement vs Baseline or Achieving Greater Than or Equal to 73 Letters at Month 6 in the Study Eye - Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and Month 6 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at Month 6 indicates a positive outcome.
Timepoint [6] 0 0
Month 6
Secondary outcome [7] 0 0
Number of Patients With a BCVA Improvement vs Baseline or Achieved Greater Than or Equal to 73 Letters at Month 24 in the Study Eye - Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and Month 12 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at Month 24 indicates a positive outcome.
Timepoint [7] 0 0
Month 24
Secondary outcome [8] 0 0
The Mean Change in Central Reading Center-assessed Central Subfield Thickness From Month 12 and Month 24 vs. Baseline by Treatment Arm - Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation. Stratification was done based on categories of baseline best corrected visual acuity & analysis was based on analysis of variance (ANOVA)
Timepoint [8] 0 0
Month 12 and Month 24
Secondary outcome [9] 0 0
The Mean Change in Patient Reported Outcomes in NEI-VFQ-25 Score (Composite Score and Subscales) at Month 6 and Month 24 Compared to Baseline - The survey consists of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. In this format scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score.
Timepoint [9] 0 0
Months 6 and 24
Secondary outcome [10] 0 0
BCVA (Letters) Mean Average Change From First Ranibizumab Treatment to Month 24 in the Study Eye for Patients Randomized to the Laser Monotherapy Arm - Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)
-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 24 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and assessed by an ANOVA model.
Timepoint [10] 0 0
Month 24

Eligibility
Key inclusion criteria
- Written informed consent must be obtained before any study assessment is performed

- Diagnosis of visual impairment exclusively due to ME secondary to BRVO

- BCVA score at Screening and Baseline between 73 and 19 letters (ETDRS)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnant or nursing (lactating) women

- Stroke or myocardial infarction less than 3 months before Screening

- Uncontrolled blood pressure defined as systolic value of >160 mm Hg or diastolic value
of >100 mm Hg at Screening or Baseline.

- Any active periocular or ocular infection or inflammation at Screening or Baseline in
either eye

- Uncontrolled glaucoma at Screening or Baseline or diagnosed within 6 months before
Baseline in either eye

- Neovascularization of the iris or neovascular glaucoma in the study eye

- Use of any systemic antivascular endothelial growth factor (anti-VEGF) drugs within 6
months before Baseline

- Panretinal laser photocoagulation within 3 months before Baseline or anticipated or
scheduled within the next 3 months following Baseline in the study eye

- Focal or grid laser photocoagulation within 4 months before Baseline in the study eye

- Use of intra- or periocular corticosteroids (including sub-Tenon) within 3 months
before Screening in the study eye

- Any use of intraocular corticosteroid implants (eg, dexamethasone [Ozurdex®],
fluocinolone acetonide [Iluvien®]) in the study eye

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
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
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 in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Parramatta
Recruitment hospital [2] 0 0
Novartis Investigative Site - Sydney
Recruitment hospital [3] 0 0
Novartis Investigative Site - Melbourne
Recruitment hospital [4] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2150 - Parramatta
Recruitment postcode(s) [2] 0 0
2000 - Sydney
Recruitment postcode(s) [3] 0 0
3002 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Canada
State/province [2] 0 0
British Columbia
Country [3] 0 0
Canada
State/province [3] 0 0
Nova Scotia
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Canada
State/province [5] 0 0
Quebec
Country [6] 0 0
Czech Republic
State/province [6] 0 0
Olomouc
Country [7] 0 0
Czech Republic
State/province [7] 0 0
Praha 10
Country [8] 0 0
Denmark
State/province [8] 0 0
Glostrup
Country [9] 0 0
France
State/province [9] 0 0
Dijon
Country [10] 0 0
France
State/province [10] 0 0
Lyon
Country [11] 0 0
France
State/province [11] 0 0
Nice
Country [12] 0 0
France
State/province [12] 0 0
Paris cedex 10
Country [13] 0 0
France
State/province [13] 0 0
Paris Cedex 19
Country [14] 0 0
France
State/province [14] 0 0
Paris
Country [15] 0 0
Greece
State/province [15] 0 0
GR
Country [16] 0 0
Greece
State/province [16] 0 0
Patras
Country [17] 0 0
Greece
State/province [17] 0 0
Thessaloniki
Country [18] 0 0
Hungary
State/province [18] 0 0
Budapest
Country [19] 0 0
Hungary
State/province [19] 0 0
Debrecen
Country [20] 0 0
Ireland
State/province [20] 0 0
Dublin 7
Country [21] 0 0
Ireland
State/province [21] 0 0
Dublin
Country [22] 0 0
Italy
State/province [22] 0 0
BO
Country [23] 0 0
Italy
State/province [23] 0 0
FI
Country [24] 0 0
Italy
State/province [24] 0 0
MI
Country [25] 0 0
Italy
State/province [25] 0 0
RM
Country [26] 0 0
Italy
State/province [26] 0 0
TO
Country [27] 0 0
Italy
State/province [27] 0 0
Bari
Country [28] 0 0
Italy
State/province [28] 0 0
Udine
Country [29] 0 0
Netherlands
State/province [29] 0 0
Leiden 2333 ZA
Country [30] 0 0
Netherlands
State/province [30] 0 0
Rotterdam
Country [31] 0 0
Netherlands
State/province [31] 0 0
Tilburg
Country [32] 0 0
Poland
State/province [32] 0 0
Bielsko-Biala
Country [33] 0 0
Poland
State/province [33] 0 0
Gdansk
Country [34] 0 0
Poland
State/province [34] 0 0
Kraków
Country [35] 0 0
Poland
State/province [35] 0 0
Lublin
Country [36] 0 0
Poland
State/province [36] 0 0
Warszawa
Country [37] 0 0
Poland
State/province [37] 0 0
Wroclaw
Country [38] 0 0
Portugal
State/province [38] 0 0
Coimbra
Country [39] 0 0
Portugal
State/province [39] 0 0
Lisboa
Country [40] 0 0
Portugal
State/province [40] 0 0
Porto
Country [41] 0 0
Slovakia
State/province [41] 0 0
Slovak Republic
Country [42] 0 0
Slovakia
State/province [42] 0 0
Banska Bystrica
Country [43] 0 0
Slovakia
State/province [43] 0 0
Bratislava
Country [44] 0 0
Spain
State/province [44] 0 0
Castilla y Leon
Country [45] 0 0
Spain
State/province [45] 0 0
Cataluña
Country [46] 0 0
Spain
State/province [46] 0 0
Comunidad Valenciana
Country [47] 0 0
Spain
State/province [47] 0 0
Galicia
Country [48] 0 0
Spain
State/province [48] 0 0
Pais Vasco
Country [49] 0 0
Spain
State/province [49] 0 0
Madrid
Country [50] 0 0
Sweden
State/province [50] 0 0
Örebro
Country [51] 0 0
Switzerland
State/province [51] 0 0
Bern
Country [52] 0 0
Switzerland
State/province [52] 0 0
Lausanne
Country [53] 0 0
Switzerland
State/province [53] 0 0
Olten
Country [54] 0 0
Switzerland
State/province [54] 0 0
Zuerich
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Surrey
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Belfast
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Birmingham
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Bristol
Country [59] 0 0
United Kingdom
State/province [59] 0 0
London
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Newcastle upon Tyne
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Plymouth
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will generate comparative data for 0.5-mg ranibizumab using PRN dosing
administered with or without adjunctive laser treatment versus laser photocoagulation (the
current standard of care) up to Month 6 in patients with visual impairment due to ME
secondary to BRVO. Additionally the results of this study will provide long-term (24-month)
safety and efficacy data for ranibizumab, administered with or without adjunctive laser
treatment in this indication.
Trial website
https://clinicaltrials.gov/show/NCT01599650
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications