Ranibizumab DosE Comparison and the Role of LAser in REtinal Vein Occlusions

Study Overview
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Brief Summary
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The primary Objective of this study is to evaluate the safety and tolerability of intraocular injections of 0.5mg or 2.0mg of ranibizumab in patients with macular edema due to retinal vein occlusion.

Detailed Description
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The secondary objectives are to assess the efficacy of 0.5mg versus 2.0mg of monthly ranibizumab injections in patients with macular edema due to retinal vein occlusion between baseline and month 6. At week 24, patients will be re-randomized to receive pro re nata (prn) ranibizumab+laser photocoagulation versus ranibizumab alone and the efficacy of both treatment options will be compared. Treatment efficacy will be assessed by comparing changes in best corrected visual acuity (BCVA) and central subfiled thickness (CST) between the treatment groups.

Official Title
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RanibizumabDosE Comparison (0.5mg and 2.0mg) and the Role of LAser in the ManagemenT of REtinal Vein Occlusion - A Pharmacodynamic Approach(RELATE)

Conditions
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Retinal Vein Occlusion

Intervention / Treatment
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* Drug: Ranibizumab 0.5mg (monthly)
* Drug: Ranibizumab 2.0mg (monthly)
* Drug: Pro re nata (prn) ranibizumab
* Procedure: Pro re nata (prn) Laser photocoagulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent and authorization of use and disclosure of protected health information Age equal to or greater than 18 years Diagnosis of macular edema due to central or branch retinal vein occlusion Foveal thickness of equal to or greater than 250 mm, as assessed by OCT Best corrected visual acuity score in the study eye of 20/40 to 20/400 inclusive (Snellen equivalents using the ETDRS protocol at a distance of 4 meters). Only one eye will be treated in the study. If both eyes are eligible, the investigator will select the eye to be enrolled. In the opinion of the investigator, decreased vision in the study eye is due to foveal thickening from vein occlusion and not from other obvious causes of decreased vision Exclusion Criteria: Scatter laser photocoagulation or macular photocoagulation within 3 months of study entry in the study eye Intraocular surgery in the study eye within 3 months of study entry Use of intraocular or periocular injection of steroids in the study eye (e.g., triamcinolone) within 4 months of study entry Previous use of an anti-VEGF drug within 3 months of study entry Cataract surgery in the study eye within 3 months of study entry; Yttrium-Aluminum-Garnet (YAG) laser capsulotomy within 1 month of study entry; or any other intraocular surgery within 3 months preceding Day 0. History of vitreoretinal surgery in the study eye within 3 months of study entry Uncontrolled glaucoma (defined as intraocular pressure ³30 mm Hg despite treatment with anti-glaucoma medications) History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 3 months of study enrollment. Pregnancy (positive pregnancy test) or lactation Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch. Have the presence of active malignancy, including lymphoproliferative disorders. Subjects with a history of fully resolved basal or squamous cell skin cancer may be enrolled. Any condition that the investigator believes would pose a significant hazard to the subject if investigational therapy were initiated. History of allergy to humanized antibodies or any component of the ranibizumab formulation Inability to comply with study or followup procedures Participation in another simultaneous medical investigation or trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BRVO- Ranibizumab 0.5mg alone<br>Branch retinal vein occlusion patients randomized to this group will receive 0.5mg of ranibizumab alone as per protocol without laser photocoagulation. | Drug: Ranibizumab 0.5mg (monthly)<br>* Branch retinal vein occlusion- Intravitreal injection of 0.5mg ranibizumab alone<br>|
| Experimental: BRVO- Pro re nata (prn) ranibizumab with laser<br>Branch retinal vein occlusion patients randomized to this group will receive 0.5mg/2.0mg of ranibizumab as per protocol, and additional laser photocoagulation if required. | Drug: Pro re nata (prn) ranibizumab<br> <br> Procedure: Pro re nata (prn) Laser photocoagulation<br> <br> |
| Experimental: BRVO- Ranibizumab 2.0mg alone<br>Branch retinal vein occlusion patients randomized to this group will receive 2.0mg of ranibizumab alone as per protocol without laser photocoagulation. | Drug: Ranibizumab 2.0mg (monthly)<br> <br> |
| Experimental: BRVO- Pro re nata (prn) ranibizumab<br>Branch retinal vein occlusion patients randomized to this group will receive 0.5mg/2.0mg of ranibizumab as per protocol, without additional laser photocoagulation. | Drug: Pro re nata (prn) ranibizumab<br> <br> |
| Experimental: CRVO- Ranibizumab 0.5mg alone<br>Central retinal vein occlusion patients randomized to this group will receive 0.5mg of ranibizumab alone as per protocol without laser photocoagulation | Drug: Ranibizumab 0.5mg (monthly)<br>* Branch retinal vein occlusion- Intravitreal injection of 0.5mg ranibizumab alone<br>|
| Experimental: CRVO- Pro re nata (prn) ranibizumab with laser<br>Central retinal vein occlusion patients randomized to this group will receive 0.5mg/2.0mg of ranibizumab as per protocol, and additional laser photocoagulation if required. | Drug: Pro re nata (prn) ranibizumab<br> <br> Procedure: Pro re nata (prn) Laser photocoagulation<br> <br> |
| Experimental: CRVO- Ranibizumab 2.0mg alone<br>Central retinal vein occlusion patients randomized to this group will receive 2.0mg of ranibizumab alone as per protocol without laser photocoagulation. | Drug: Ranibizumab 2.0mg (monthly)<br> <br> |
| Experimental: CRVO- Pro re nata (prn) ranibizumab<br>Central retinal vein occlusion patients randomized to this group will receive 0.5mg/2.0mg of ranibizumab as per protocol, without additional laser photocoagulation. | Drug: Pro re nata (prn) ranibizumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Ocular and Non-ocular Adverse Events. |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to Month 6 in Best Corrected Visual Acuity in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab |  | Baseline to month 6 | 
| Mean Change From Month 6 to Month 36 in Best Corrected Visual Acuity in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone. |  | Month 6- Month 36 | 
| Mean Change From Baseline to Month 6 in Central Subfield Thickness in Patients Treated With 0.5mg Versus 2.0mg of Ranibizumab |  | Baseline to month 6 | 
| Mean Change From Month 6 to Month 36 in Central Subfield Thickness in Patients Treated With Prn Ranibizumab+Laser Photocoagulation Versus Prn Ranibizumab Alone. |  | Month 6- Month 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RVO, BRVO, CRVO, Vein occlusion