Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With Central Retinal Vein Occlusion (CRVO)

Study Overview
=================
Brief Summary
-----------------
This clinical trial is designed to compare ranibizumab in comparison with Dexamethasone implant® after 6 months of treatment. In the study arm Lucentis will be given monthly in a pro re nata scheme whereas the comparator Dexamethasone implant is given once at Month 0 with sham injections PRN afterwards.

Official Title
-----------------
A 6-month Multicenter, Randomized, Double-masked Phase IIIb-study Comparing the Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With Visual Impairment Due to Macular Edema Following Central Retinal Vein Occlusion (CRVO)

Conditions
-----------------
Visual Impairment, Macular Edema, Central Retinal Vein Occlusion

Intervention / Treatment
-----------------
* Drug: Ranibizumab
* Drug: Dexamethasone implant and sham injections


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients diagnosed with visual impairment due to macular edema following CRVO Diagnosis of CRVO at maximum 6 months prior to Screening BCVA using ETDRS charts of 20/40 to 20/400 in the study eye Exclusion Criteria: Media clarity, pupillary dilation and patient cooperation not sufficient for adequate fundus photographs Central retinal thickness (CRT) < 250 µm in the study eye Prior episode of RVO in the study eye Active formation of new vessels in the study eye Anti-VEGF-treatment in the study or the fellow eye 3 months prior to Baseline IOP ≥ 30mmHg or uncontrolled glaucoma; patients may be re-screened after 1 month if they have undergone glaucoma treatment Improvement of > 10 letters on BCVA between Screening and Baseline Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranibizumab<br> | Drug: Ranibizumab<br> <br> |
| Active Comparator: Standard of Care<br> | Drug: Dexamethasone implant and sham injections<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Average BCVA Change From Month 1 Through Month 6 to Baseline | the average of the changes in BCVA (letters) from baseline to any post-baseline visit, i.e. the mean of six differences to baseline for the six post-baseline visits at month 1 to 6. 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 ETDRS visual acuity score of 85 is pproximately 20/20. An increased score indicates improvement in acuity | Baseline, month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean BCVA Change at Month 6 | The analysis was performed by an analysis of covariance (ANCOVA) model with average change in BCVA (letters) from Visit 1 through Visit 6 as dependent variable, and with the factors center, treatment and covariate baseline BCVA as predictors | Baseline, month 6 | 
| Number of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters | 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 ETDRS visual acuity score of 85 is approximately 20/20. An increased score indicates improvement in acuity. This outcome assessed the number of participants who gained 15, 10 or 5 more letters of visual acuity at month 6 as compared with baseline | Baseline, 6 month | 
| Time to Achieve a Significant Improvement ≥ 15 Letters | The time was analyzed by the Kaplan-Maier-Method, adjusting the calculation for dropouts | Baseline, month 6 | 
| Change Over Time in BCVA | The analysis was performed by an analysis of covariance (ANCOVA) model with average change in BCVA (letters) from Visit 1 through Visit 6 as dependent variable, and with the factors center, treatment and covariate baseline BCVA as predictors | Baseline, month 6 | 
| Change Over Time of the Central Retinal Thickness (CRT) | Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation | Baseline, month 6 | 
| Changes in the Quality of Life According to the National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) Questionnaires | The VFQ-25 composite and subscale scores range from 0 to 100, a higher score indicating better functioning. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated improvement in quality of life due to vision function | Baseline, month 6 | 
| Changes in the Quality of Life According to the Short Form (36) Health Survey (SF-36)Questionnaires | SF-36 summary measures are norm-based scores with mean = 50 and SD = 10. Higher scores indicate better health | Baseline, month 6 | 
| Changes in the Quality of Life According to Euro Quality of Life (EQ-5D) Questionnaires | The EQ-5D visual analog scale ranges from 0 to 100, 0 representing the worst and 100 the best imaginable health state. | Baseline, month 6 | 
| Increase Rate of the Internal Ocular Pressure (IOP ) : Patients With ≥10% Increase in IOP Compared to Baseline | The proportion of patients with ≥ 10% increase in Internal Ocular Pressure (IOP) compared to baseline at any post-baseline visit. | Baseline, month 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Central retinal vein occlusion, Visual impairment, macular edema, Dexamethasone implant, Ranibizumab