Bevacizumab Versus Ranibizumab in Treatment of Macular Edema From Vein Occlusion (CRAVE)

Comparison of Anti-vascular Endothelial Growth Factors Agents in the Treatment of Macular Edema Following Retinal Vein Occlusion

Antagonists of the vascular endothelial growth factor (VEGF) pathway are effective in treating macular edema resulting from retinal vein occlusion (RVO). In the eye, the two most widely used anti-VEGF agents are ranibizumab and bevacizumab. Only ranibizumab has been FDA-approved for the treatment of macular edema from RVO, however bevacizumab has been used off-label by many ophthalmologists with good success. Furthermore, the cost of bevacizumab is less than one-tenth the cost of ranibizumab. Here the investigators conduct a six month randomized, prospective interventional trial comparing the effectiveness of ranibizumab with bevacizumab in the treatment of macular edema from RVO. Primary outcome measures are change in central retinal thickness. Secondary measures are change in visual acuity from baseline and change in angiographic properties of macular lesions from baseline after treatment.

Study Overview

• Status: Completed
• Conditions: Macular Edema; Retinal Vein Occlusion
• Intervention / Treatment: Drug: Intravitreal injection of bevacizumab; Drug: Intravitreal injection of ranibizumab (0.5 mg per dose)

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • The Retina Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to provide informed consent
• Visual acuity of 20/40 - 20/320 in the study eye (regardless of relative APD)
• Central foveal thickness (CFT) of > 250 microns as assessed by OCT (see below)
• Diagnosis of retinal vein occlusion in the past 9 months
• Age over 50 years

Exclusion Criteria:

• History of previous intraocular surgery in the study eye, including pars plana vitrectomy (but not including uncomplicated cataract surgery), within 60 days of the screening visit
• Inability to make study visits
• Uncontrolled glaucoma in the study eye (defined as intraocular pressure (IOP) ≥ 25 mmHg) despite treatment with two or more topical pharmacological anti-glaucomatous medication)
• Pregnancy or lactation
• Evidence of any diabetic retinopathy on exam or history of diabetic macular edema within 12 weeks of study onset
• Any intravitreal injections within 12 weeks of study onset
• Prior retinal vein occlusion
• History of pan-retinal photocoagulation within 3 months of study onset or anticipated within 4 months after study onset
• History of cerebrovascular event or myocardial infarction within 3 months of study onset

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
Active Comparator: Ranibizumab	Drug: Intravitreal injection of ranibizumab (0.5 mg per dose); 0.5 mg per dose, delivered monthly by intravitreal injection for six months
Active Comparator: Bevacizumab	Drug: Intravitreal injection of bevacizumab; 1.25 mg per dose, delivered monthly by intravitreal injection for six months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in central retinal thickness	central thickness is measured using optical coherence tomography (OCT)	six months compared to baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in best-corrected Snellen visual acuity	best-corrected Snellen visual acuity (BCVA) is the best visual acuity measured using a standard Snellen eye chart at 20 feet between (1) uncorrected vision, (2) vision with current eyeglasses or (3) pinholed visual acuity.	six months compared to baseline
change in fluorescein angiogram	fluorescein angiograms will measure area of peripheral nonperfusion. This will be interpreted by a designated physician at each testing center.	six months compared to baseline

Collaborators and Investigators

• Sponsor: Barnes Retina Institute
• Collaborators: Massachusetts Eye and Ear Infirmary; Long Island Vitreoretinal Consultants; Illinois Retina Associates; Mid Atlantic Retina; Retina Associates of Florida, P.A.; Kresge Eye Institute; Retina Associates, Kansas City

Publications and helpful links

General Publications

• Rajagopal R, Shah GK, Blinder KJ, Altaweel M, Eliott D, Wee R, Cooper B, Walia H, Smith BT, Joseph DP. Bevacizumab Versus Ranibizumab in the Treatment of Macular Edema Due to Retinal Vein Occlusion: 6-Month Results of the CRAVE Study. Ophthalmic Surg Lasers Imaging Retina. 2015 Sep;46(8):844-50. doi: 10.3928/23258160-20150909-09.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: September 1, 2011
• First Submitted That Met QC Criteria: September 2, 2011
• First Posted (Estimate): September 5, 2011

Study Record Updates

• Last Update Posted (Actual): October 27, 2017
• Last Update Submitted That Met QC Criteria: October 26, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: bevacizumab; macular edema; vein occlusion; ranibizumab; vascular endothelial growth factor
• 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; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab; Bevacizumab
• Other Study ID Numbers: CRAVE1