Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) (SCORE2)

June 11, 2021 updated by: The Emmes Company, LLC

Study of COmparative Treatments for REtinal Vein Occlusion 2 [SCORE2]: a Multicenter, Prospective, Randomized Non-inferiority Trial of Eyes With Macular Edema Secondary to Central Retinal Vein Occlusion, Comparing Intravitreal Bevacizumab Every 4 Weeks With Intravitreal Aflibercept Every 4 Weeks.

SCORE2 is a multicenter, prospective, randomized, phase III clinical trial in which all participants enrolled will be followed for up to 2.5 years. SCORE2 is designed as a non-inferiority trial, with study eyes randomized to intravitreal bevacizumab (1.25 mg) every 4 weeks vs. intravitreal aflibercept (2.0 mg) every 4 weeks. SCORE2 aims to determine if bevacizumab is non-inferior to aflibercept for the treatment of macular edema associated with central retinal vein occlusion (CRVO), with the primary outcome of visual acuity measured at Month 6.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The primary objective of SCORE2 is to test for non-inferiority based on mean change from baseline in visual acuity letter score at Month 6 for eyes randomized to intravitreal bevacizumab every 4 weeks compared with eyes randomized to intravitreal aflibercept every 4 weeks using a non-inferiority margin of 5 letters.

Secondary objectives of SCORE2 are to:

  • compare the bevacizumab and the aflibercept groups with regards to central retinal thickness, as measured with spectral domain optical coherence tomography (SD-OCT), at Month 6 and change between baseline and Month 6;
  • assess Month 12 visual acuity and SD-OCT outcomes associated with different dosing strategies after Month 6 in participants who respond well to treatment;
  • assess Month 12 visual acuity and SD-OCT outcomes associated with alternative treatment strategies after Month 6 in participants who respond poorly to treatment;
  • compare area of retinal ischemia and rates of neovascular complications of CRVO in the bevacizumab vs. aflibercept groups;
  • add to our knowledge of the safety profile of these anti-vascular endothelial growth factor (VEGF) medications in the setting of eyes with macular edema secondary to CRVO;
  • conduct a cost effectiveness analysis comparing intravitreal bevacizumab to intravitreal aflibercept to assess the economic implications from a payor perspective using decision analytic methods.

Other exploratory aims of SCORE2 are to:

  • investigate the correlation of features identified through SD-OCT segmentation analysis, such as the inner segment-outer segment (IS-OS) junction (also known as the ellipsoid zone), with such characteristics as visual acuity and central retinal thickness;
  • investigate the correlation of area of peripheral retinal nonperfusion from widefield fluorescein angiography with visual acuity and central retinal thickness, and the prognostic value of baseline peripheral and central retina perfusion status in predicting disease course and treatment responsiveness;
  • investigate the correlation of features on adaptive optics imaging with such characteristics as visual acuity and central retinal thickness.

Study Type

Interventional

Enrollment (Actual)

362

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85014
        • Retinal Consultants of AZ
      • Tucson, Arizona, United States, 85704
        • Retina Centers, P.C.
    • California
      • Mountain View, California, United States, 94040
        • Northern California Retina Vitreous Associates
      • Oakland, California, United States, 94609
        • East Bay Retina Consultants, Inc.
      • Palm Desert, California, United States, 92211
        • Southern California Desert Retina Consultants
      • Sacramento, California, United States, 95817
        • University of California Davis, Medical Center
      • Sacramento, California, United States, 95819
        • Retinal Consultants Medical Group, Inc.
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • Connecticut
      • New London, Connecticut, United States, 06320
        • New England Retina Associates
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
        • Retina Group of Florida
      • Fort Myers, Florida, United States, 33912
        • National Ophthalmic Research Institute
      • Jacksonville, Florida, United States, 32209
        • University of Florida, Dept of Ophthalmology
      • Lakeland, Florida, United States, 33805
        • Florida Retina Consultants
      • Sarasota, Florida, United States, 34239
        • Sarasota Retina Institute
      • Winter Haven, Florida, United States, 33880
        • Center for Retina and Macular Disease
      • Winter Haven, Florida, United States, 33880
        • Florida Retina Consultants
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Eye Center
      • Augusta, Georgia, United States, 30909
        • Southeast Retina Center
      • Marietta, Georgia, United States, 30060
        • Georgia Retina, P.C.
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Illinois Eye and Ear Infirmary UIC Dept. of Ophthalmology
    • Indiana
      • Indianapolis, Indiana, United States, 46290
        • Thomas A. Ciulla, MD, PC
    • Kansas
      • Leawood, Kansas, United States, 66211
        • Sabates Eye Centers
      • Shawnee Mission, Kansas, United States, 66204
        • Retina Associates, PA
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University Of Kentucky
      • Lexington, Kentucky, United States, 40509
        • Retina Associates of Kentucky
      • Paducah, Kentucky, United States, 42001
        • Paducah Retinal Center
    • Maryland
      • Baltimore, Maryland, United States, 21237
        • Elman Retina Group, PA
      • Chevy Chase, Maryland, United States, 20815
        • The Retina Group of Washington
      • Glen Burnie, Maryland, United States, 21061
        • Elman Retina Group, P.A.
      • Hagerstown, Maryland, United States, 21740
        • Cumberland Valley Retina Consultants
      • Pikesville, Maryland, United States, 21208
        • Elman Retina Group, P.A.
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
      • Jackson, Michigan, United States, 49202
        • TLC Eyecare & Laser Centers
    • Minnesota
      • Minneapolis, Minnesota, United States, 55435
        • Vitreoretinal Surgery
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • Saint Louis, Missouri, United States, 63128
        • The Retina Institute
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • UNMC Truhlsen Eye Institute
    • Nevada
      • Las Vegas, Nevada, United States, 89144
        • Retina Consultants of Nevada
    • New Jersey
      • Lawrenceville, New Jersey, United States, 08648
        • Delaware Valley Retina Associates
      • New Brunswick, New Jersey, United States, 08901
        • NJ Retina
    • New York
      • New York, New York, United States, 10003
        • New York Eye and Ear Infirmary
      • Rochester, New York, United States, 14620
        • Retina Associates of Western New York
      • Rochester, New York, United States, 14642
        • University of Rochester Flaum Eye Institute
      • Syracuse, New York, United States, 13224
        • Retina Vitreous Surgeon of CNY, PC
    • North Carolina
      • Charlotte, North Carolina, United States, 28210
        • Charlotte Eye Ear Nose & Throat Associates, P.A.
      • Statesville, North Carolina, United States, 28677
        • Charlotte Eye Ear Nose & Throat Associates, P.A.
    • Ohio
      • Cleveland, Ohio, United States, 44122
        • Retina Associates of Cleveland, Inc.
      • Columbus, Ohio, United States, 43212
        • The Ohio State University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Dean McGee Eye Institute
    • Oregon
      • Portland, Oregon, United States, 97210
        • Retina Northwest, PC
      • Portland, Oregon, United States, 97239
        • Casey Eye Institute / OHSU
    • Pennsylvania
      • Monroeville, Pennsylvania, United States, 15146
        • Retina Vitreous Consultants
      • Philadelphia, Pennsylvania, United States, 19104
        • Scheie Eye Institute
    • South Carolina
      • Florence, South Carolina, United States, 29501
        • Carolinas Centers for Sight, PC
      • West Columbia, South Carolina, United States, 29169
        • Palmetto Retina Center
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Black Hills Regional Eye Institute
    • Tennessee
      • Knoxville, Tennessee, United States, 37909
        • Southeastern Retina Associates, PC
      • Nashville, Tennessee, United States, 37203
        • Tennessee Retina, PC
      • Nashville, Tennessee, United States, 37232-8808
        • Vanderbilt Eye Institute
    • Texas
      • Abilene, Texas, United States, 79606
        • Retina Research Institute of Texas
      • Arlington, Texas, United States, 76012
        • Texas Retina Associates
      • Austin, Texas, United States, 78705
        • The Retina Research Center
      • Dallas, Texas, United States, 75231
        • Texas Retina Associates
      • Houston, Texas, United States, 77030
        • Retina Consultants of Houston, PA
      • Houston, Texas, United States, 77025
        • Charlotte Eye Ear Nose & Throat Associates, P.A.
      • Houston, Texas, United States, 77025
        • Retina & Vitreous of Texas
      • McAllen, Texas, United States, 78503
        • Valley Retina Institute, PA
      • San Antonio, Texas, United States, 78240
        • Medical Center Ophthalmology Associates
      • San Antonio, Texas, United States, 78240
        • Retinal Consultants of San Antonio
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • The Retina Group of Washington
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • University of Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Participants must have center-involved macular edema secondary to CRVO. Eyes may be enrolled as early as the time of diagnosis of the macular edema. The definition of CRVO used in SCORE will also be used for the purposes of SCORE2: a CRVO is defined as an eye that has retinal hemorrhage or other biomicroscopic evidence of retinal vein occlusion (e.g., telangiectatic capillary bed) and a dilated venous system (or previously dilated venous system) in all 4 quadrants.
  • Due to the similarities of a hemiretinal vein occlusion (HRVO) to CRVO,HRVO will be classified as CRVO for the purposes of this clinical trial. Eyes classified as having a HRVO will be limited to no more than 25% of the planned sample size. A HRVO is defined as an eye that has retinal hemorrhage or other biomicroscopic evidence of retinal vein occlusion (e.g. telangiectatic capillary bed) and a dilated venous system (or previously dilated venous system) in 5 or more clock hours but less than all 4 quadrants. Typically, a HRVO is a retinal vein occlusion that involves 2 altitudinal quadrants.
  • E-Early Treatment Diabetic Retinopathy Study (ETDRS)visual acuity score of greater than or equal to 19 letters (approximately 20/400) and less than or equal to 73 letters (approximately 20/40) by the ETDRS visual acuity protocol. The investigator must believe that a study eye with visual acuity between 19 and 33 letters is perfused.
  • Retinal thickness on SD-OCT measurement, defined as central subfield thickness of 300 µm or greater. If the SD-OCT measurement is taken from a Heidelberg Spectralis Machine, the central subfield thickness should be 320 µm or greater.
  • Media clarity, pupillary dilation and participant cooperation sufficient for adequate fundus photographs.

Exclusion Criteria:

  • A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., chronic alcoholism or drug abuse, personality disorder or use of major tranquilizers indicating difficulty in long term follow-up, likelihood of survival of less than 12 months).
  • Participation in an investigational trial within 30 days of study entry that involved treatment with any drug that has not received regulatory approval at time of study entry.
  • History of allergy to any anti-VEGF agent, corticosteroid, or component of the delivery vehicle.
  • The participant will be moving out of the area of the clinical site to an area not covered by another clinical site during the 12 months of the study.
  • Positive urine pregnancy test: all women of childbearing potential (those who are pre-menopausal and not surgically sterilized) may participate only if they have a negative urine pregnancy test, and if they do not intend to become pregnant during the timeframe of the study. Women who are sexually active with a male partner must agree to use at least one of the following birth control methods: hormonal therapy such as oral, implantable or injectable chemical contraceptives; mechanical therapy such as spermicide in conjunction with a barrier such as a condom or diaphragm; intrauterine device (IUD); or surgical sterilization of partner.
  • Women who are breast-feeding.
  • Examination evidence of vitreoretinal interface disease (e.g., vitreomacular traction, epiretinal membrane), either on clinical examination or OCT thought to be contributing to macular edema.
  • An eye that, in the investigator's opinion, would not benefit from resolution of macular edema such as eyes with foveal atrophy, dense pigmentary changes or dense subfoveal hard exudates.
  • Presence of an ocular condition that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., age-related macular degeneration, uveitis or other ocular inflammatory disease, neovascular glaucoma, iris neovascularization, Irvine-Gass Syndrome, prior macula-off rhegmatogenous retinal detachment).
  • Presence of a substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., a 20/40 cataract).
  • History of laser photocoagulation for macular edema within 3 months prior to randomization.
  • History of intravitreal corticosteroid within 4 months of randomization.
  • Intravitreal anti-VEGF injection within 2 months of randomization. Note: Enrollment will be limited to no more than 25% of the planned sample size with any history of anti-VEGF treatment. Once this number of eyes has been enrolled, any history of anti-VEGF treatment will be an exclusion criterion. For enrollment of study eyes with prior intravitreal anti-VEGF agents, in the opinion of the investigator, the treatment response to prior anti-VEGF treatment must be either incomplete or the study eye had developed recurrent CRVO-associated macular edema, such that the study eye would benefit from additional anti-VEGF treatment.
  • History of peribulbar or retrobulbar corticosteroid use for any reason within 2 months prior to randomization.
  • History of panretinal scatter photocoagulation (PRP) or sector laser photocoagulation within 3 months prior to randomization or anticipated within the next 3 months following randomization.
  • History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within 4 months prior to randomization or anticipated within the next 6 months following randomization.
  • History of yttrium aluminum garnet (YAG) capsulotomy performed within 2 months prior to randomization.
  • Aphakia.
  • Presence of an anterior chamber intraocular lens
  • Examination evidence of external ocular infection, including conjunctivitis, chalazion or significant blepharitis.
  • History of macular detachment.
  • Examination evidence of any diabetic retinopathy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: aflibercept
2.0 mg aflibercept every 4 weeks
Drug: aflibercept
Other Names:
  • EYLEA
Active Comparator: bevacizumab
1.25 mg bevacizumab every 4 weeks
Drug: bevacizumab
Other Names:
  • Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change From Baseline in Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Letter Score at Month 6
Time Frame: Month 0 to 6
The primary analysis is based on observed data at 6 months. The measure is calculated by subtracting the baseline visual acuity letter score from the month 6 visual acuity letter score. The participant is refracted for best corrected vision, and then reads single letters on an electronic visual acuity tester at a 3 meter distance according to a specific algorithm. A letter score is provided that ranges from 0 (unable to ready any letters) to 100. A visual acuity letter score of 85 corresponds to a visual acuity of 20/20 as a Snellen equivalent.
Month 0 to 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Study Eyes With Gain of ≥15 Letters in Visual Acuity Letter Score at Month 6
Time Frame: Month 0 to 6
The measure is the number of study eyes that gained at least 15 letters in their visual acuity letter score at month 6
Month 0 to 6
Number of Study Eyes With Visual Acuity Letter Score of 70 or Better at Month 6
Time Frame: Month 0 to 6
The measure is the number of study eyes with a visual acuity letter score of 70 (Snellen equivalent of 20/40) or better at month 6
Month 0 to 6
Mean Spectral-domain Optical Coherence Tomography Central Subfield Thickness
Time Frame: Month 0 to 6
The measure is the mean central subfield thickness at month 6 measured by spectral-domain optical coherence tomography
Month 0 to 6
Mean Change From Baseline in Spectral Domain Optical Coherence Tomography Central Subfield Thickness at Month 6
Time Frame: Month 0 to 6
The measure is calculated by subtracting the baseline central subfield thickness from the month 6 central subfield thickness
Month 0 to 6
Number of Study Eyes With Central Subfield Thickness <300 μm, no Subretinal Fluid, no Intraretinal Fluid, and no Cystoid Spaces
Time Frame: Month 0 to 6
The measure is the number of study eyes with central subfield thickness <300 μm, no subretinal fluid, no intraretinal fluid, and no cystoid spaces at month 6
Month 0 to 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Emmes Company, LLC

Collaborators

National Eye Institute (NEI)
University of Wisconsin, Madison
Milton S. Hershey Medical Center

Investigators

  • Study Chair: Ingrid U Scott, M.D., M.P.H., Penn State College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2014

Primary Completion (Actual)

November 1, 2016

Study Completion (Actual)

March 1, 2021

Study Registration Dates

First Submitted

October 22, 2013

First Submitted That Met QC Criteria

October 22, 2013

First Posted (Estimate)

October 25, 2013

Study Record Updates

Last Update Posted (Actual)

June 22, 2021

Last Update Submitted That Met QC Criteria

June 11, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCORE2
  • U10EY023529 (U.S. NIH Grant/Contract)
  • U10EY023533 (U.S. NIH Grant/Contract)
  • U10EY023521 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

SCORE2 will follow specific plans for sharing of research data. After analysis, the final data set can be provided after appropriate procedures are implemented to preserve the anonymity of the records, specifically where protected health information (PHI) is required. Upon request, anonymized data will be shared under confidentiality agreements with researchers interested in the project.

IPD Sharing Time Frame

The time frame will be determined

IPD Sharing Access Criteria

Confidentiality agreements will be required before anonymized data will be shared.

Study Data/Documents

  1. Study Protocol
    Information identifier: PB2016-103333
    Information comments: SCORE2 Protocol Version 3.0 (the Identifier for the appendices is PB2016-103334)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Central Retinal Vein Occlusion

Clinical Trials on bevacizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in United Kingdom

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe