Ranibizumab for Macular Edema Secondary to Branch Retinal Vein Occlusion in Patients With Fair Vision

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the effect of ranibizumab for the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO) in patients with initial fair visual acuity.

Detailed Description
-----------------
Lucentis was approved for ME due to BRVO based on the results from BRAVO study. The inclusion criteria in BRAVO was best corrected visual acuity (BCVA) 20/40 to 20/320. Therefore, the patients with VA better than 20/40 who are out of inclusion criteria of BRAVO study had no treatment and just wait to reach spontaneous improvement. But, there is unmet needs of these patients and, in actual clinical practice, many retina specialists treat these patients with Ranibizumab. These patients have been experiencing VA improvement after the injection. Based on these clinical backgrounds, the investigator wants to suggest the treatment guidelines in these patients group, which is, early treatment of ranibizumab would be effective and increase patients' QOL. In other words, there are many experiences in these cases among ophthalmologists, but there have been no clinical trials that can endorse the treatments. To confirm the efficacy of ranibizumab in patients with initial fair vision, the investigators started the prospective randomized clinical trial on the efficacy and safety of ranibizumab for the patients.

Official Title
-----------------
Phase 4 Study of Ranibizumab for the Treatment of Visual Impairment Due to Macular Edema Secondary to Branch Retinal Vein Occlusion in Patients With Initial Fair Visual Acuity

Conditions
-----------------
Branch Retinal Vein Occlusion, Macular Edema

Intervention / Treatment
-----------------
* Drug: Ranibizumab
* Device: Sham injection
* Procedure: Rescue laser


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Foveal center-involving macular edema secondary to BRVO diagnosed within 12 months before study enrollment ETDRS chart BCVA: 63 to 77 letters (20/32 to 20/50 Snellen equivalent) CFT >= 300 um (mean of measurements obtained at screening and Day 0) Signed consent informed male or female, age ≥18 years old Exclusion Criteria: Prior episode of RVO: Past history of RVO in the study eye diagnosed before 1 year of study enrollment. BCVA improvement >10 letters between screening and Day 0 History of other ocular diseases (e.g. diabetic retinopathy, age-related macular degeneration) Laser treatment within 3 months before baseline Intraocular corticosteroid use within 3 months before baseline Anti-vascular endothelial growth factor (VEGF) treatment in the study or fellow eye within 3 months before baseline Intraocular surgery other than cataract surgery, Cataract surgery within 6 months before baseline Stroke or myocardial infarction ≤3 months before baseline Pregnancy or plan to have baby in female

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranibizumab group<br>Patients will receive three monthly injections of 0.5 mg of Lucentis (0.05 ml), followed by retreatment/rescue laser as needed. | Drug: Ranibizumab<br>* Loading dose: three monthly intravitreal injections of ranibizumab 0.5 mg Lucentis stop criteria: V/A ≥20/20 and complete disappearance of macular edema Retreatment: visual loss of 5 or more letter compared to previous visit<br>* Other names: Lucentis(ranibizumab), 3mg/0.3ml;Procedure: Rescue laser<br>* In the Lucentis group: performed if BCVA < 20/40 or CFT ≥ 350um despite of 3 sessions of previous Lucenis injection from Month 6 In the standard of care group: performed if BCVA < 20/40 or CFT ≥ 350um from Month 3<br>|
| Sham Comparator: Standard of care group<br>Patients will receive three monthly sham injections, followed by retreatment/rescue laser as needed. | Device: Sham injection<br>* Three monthly sham injections followed by retreatment (sham injections) as needed Stop criteria: V/A ≥20/20 and complete disappearance of macular edema Retreatment: visual loss of 5 or more letter compared to previous visit<br>Procedure: Rescue laser<br>* In the Lucentis group: performed if BCVA < 20/40 or CFT ≥ 350um despite of 3 sessions of previous Lucenis injection from Month 6 In the standard of care group: performed if BCVA < 20/40 or CFT ≥ 350um from Month 3<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to achieve an improvement of 10 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters in best-corrected visual acuity |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline ETDRS letter score over time |  | 6 months and 1 year | 
| Percentage of patients gaining 10 or more letters in ETDRS letter score from baseline BCVA |  | 6 months and 1 year | 
| Percentage of patients gaining < 10 letters in ETDRS letter score from baseline BCVA |  | 6 months and 1 year | 
| Percentage of patients losing < 10 letters in ETDRS letter score from baseline BCVA |  | 6 months and 1 year | 
| Proportion of patients with who at least maintain baseline BCVA |  | 6 months and 1 year | 
| Percentage of patients with central foveal thickness (CFT) of < 300 um |  | 6 months and 1 year | 
| Safety outcomes | Frequency, type, and severity of adverse reactions | 6 months and 1 year | 
| Mean change from baseline CFT over time |  | 6 months and 1 year | 
| Mean change from baseline in National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) distance activities subscale score |  | 6 months and 1 year | 
| Mean change from baseline in contrast sensitivity |  | 6 months and 1 year | 
| Mean change from baseline in multifocal electroretinogram (mfERG) P1 amplitude |  | 6 months and 1 year | 
| Percentage of patients losing 10 or more letters in ETDRS letter score from baseline BCVA |  | 6 months and 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Branch retinal vein occlusion, Macular edema, Ranibizumab