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

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

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.

Study Overview

• Status: Terminated
• Conditions: Macular Edema; Branch Retinal Vein Occlusion
• Intervention / Treatment: Drug: Ranibizumab; Procedure: Rescue laser; Device: Sham injection

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Gyunggi-do
    • Seongnam, Gyunggi-do, Korea, Republic of, 463-707
      • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Foveal center-involving macular edema secondary to BRVO diagnosed within 12 months before study enrollment
2. ETDRS chart BCVA: 63 to 77 letters (20/32 to 20/50 Snellen equivalent)
3. CFT >= 300 um (mean of measurements obtained at screening and Day 0)
4. Signed consent informed
5. male or female, age ≥18 years old

Exclusion Criteria:

1. Prior episode of RVO: Past history of RVO in the study eye diagnosed before 1 year of study enrollment.
2. BCVA improvement >10 letters between screening and Day 0
3. History of other ocular diseases (e.g. diabetic retinopathy, age-related macular degeneration)
4. Laser treatment within 3 months before baseline
5. Intraocular corticosteroid use within 3 months before baseline
6. Anti-vascular endothelial growth factor (VEGF) treatment in the study or fellow eye within 3 months before baseline
7. Intraocular surgery other than cataract surgery, Cataract surgery within 6 months before baseline
8. Stroke or myocardial infarction ≤3 months before baseline
9. Pregnancy or plan to have baby in female

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ranibizumab group; Patients will receive three monthly injections of 0.5 mg of Lucentis (0.05 ml), followed by retreatment/rescue laser as needed.	Drug: Ranibizumab; 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; Other Names: Lucentis(ranibizumab), 3mg/0.3ml; Procedure: Rescue laser; 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
Sham Comparator: Standard of care group; Patients will receive three monthly sham injections, followed by retreatment/rescue laser as needed.	Procedure: Rescue laser; 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; Device: Sham injection; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Collaborators: Samsung Medical Center; Novartis
• Investigators: Principal Investigator: Kyu Hyung Park, M.D., Seoul National Univeristy Bundang Hospital; Principal Investigator: Se Woong Kang, M.D., Samsung Medical Center

Publications and helpful links

General Publications

• Campochiaro PA, Heier JS, Feiner L, Gray S, Saroj N, Rundle AC, Murahashi WY, Rubio RG; BRAVO Investigators. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010 Jun;117(6):1102-1112.e1. doi: 10.1016/j.ophtha.2010.02.021. Epub 2010 Apr 15.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: February 18, 2013
• First Submitted That Met QC Criteria: February 19, 2013
• First Posted (Estimate): February 20, 2013

Study Record Updates

• Last Update Posted (Actual): September 19, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Ranibizumab; Macular edema; Branch retinal vein occlusion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Macular Degeneration; Macular Edema; Retinal Vein Occlusion; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: B-1207-162-005 (Other Identifier: Seoul National University Bundang Hospital)