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Intravitreal Ranibizumab for Vitreous Hemorrhage Due to Proliferative Diabetic Retinopathy (N)

Phase 2
Completed
Conditions
Vitreous Hemorrhage
Proliferative Diabetic Retinopathy
Interventions
Drug: Saline
Registration Number
NCT00996437
Lead Sponsor
Jaeb Center for Health Research
Brief Summary

This study is being conducted to determine if intravitreal injections of ranibizumab decrease the proportion of eyes in which vitrectomy is performed compared with saline injections in eyes presenting with vitreous hemorrhage from proliferative diabetic retinopathy.

Detailed Description

In mild to moderate cases of vitreous hemorrhage, panretinal photocoagulation (PRP) is performed when possible to achieve regression of new vessels or at least stabilization of the neovascularization with no further growth in order to decrease the probability of subsequent vitreous hemorrhage while spontaneous absorption of the hemorrhage occurs. In cases in which the hemorrhage is too dense to apply PRP, vitrectomy is considered to remove the hemorrhage and provide a clear media for application of PRP (often as endolaser photocoagulation) as well as eliminate extensive neovascularization and relieve traction retinal detachments. Pars plana vitrectomy was introduced in the 1970s as a surgical intervention in diabetes for non-clearing vitreous hemorrhage, traction retinal detachment or very severe proliferative diabetic retinopathy (PDR). The goal of vitrectomy in such eyes is to remove the hemorrhage and provide a clear media for application of PRP (often as endolaser photocoagulation) as well as eliminate extensive neovascularization and relieve traction retinal detachments. Many advances in instrumentation and technique have resulted in a dramatic reduction in complications over the last few decades, but surgical complications remain including the following: neovascular glaucoma, retinal detachment, fibrinoid syndrome, endophthalmitis and hypotony with subsequent phthisis bulbi. Recovery for the subject can take up to 6 weeks.

Increased vascular endothelial growth factor (VEGF) levels have been demonstrated in the retina and vitreous of human eyes with diabetic retinopathy, especially PDR. VEGF has been demonstrated to increase vessel permeability by increasing the phosphorylation of tight junction proteins, and has been shown to increase retinal vascular permeability in in vivo models. Anti-VEGF therapy, therefore, may represent a useful therapeutic modality which targets the underlying pathogenesis of PDR while vitreous hemorrhage clears to facilitate the placement of PRP, potentially avoiding vitrectomy.

This study is designed to determine if intravitreal injections of ranibizumab will facilitate clearing of vitreous hemorrhage and avoidance of vitrectomy and its potential complications. Compared with a surgical intervention, use of an intravitreal agent associated with fewer vitrectomies would be preferable because of the reduced costs, reduced time to treatment, reduced intervention time, relatively low risk of side effects, and reduced recovery time. An intravitreal agent also would be a useful alternative for patients who are unwilling to undergo surgery. Furthermore, the study will determine the safety of this medication in the setting of PDR.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
261
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Saline InjectionSalineSaline injection at baseline, 4 and 8 weeks
RanibizumabRanibizumabIntravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
Primary Outcome Measures
NameTimeMethod
Treatment or "Failure" Defined as Vitrectomywithin 112 days of randomization

The cumulative probabilities of vitrectomy by 16 weks (112 days) in each group were computed using the life-table method. The treatment group comparison was made using the log-rank test. Data were censored at the time point of the participant's last completed visit.

Safety (Injected-related, Ocular Drug-related and Systemic Drug-related)Baseline to 16 weeks
Secondary Outcome Measures
NameTimeMethod
Severe Visual Acuity Loss (Defined as <20/200)4,8 and 12 weeks
Very Severe Visual Acuity Loss (Defined as <20/800)4,8 and 12 weeks
Extent of Vitreous Hemorrhage Measured by Optical Coherence Tomography Signal Strength4, 8 and 12 weeks

Optical coherence tomography signal strength was evaluated as a potential indicator of vitreous hemorrhage density in an exploratory analysis. This analysis included only eyes with Optical Coherence Tomography (OCT) signal strength equals to 0 at baseline.

Visual Acuity Adjusted for the Baseline Acuity Regardless of Vitrectomy Status4, 8 and 12 weeks

Visual acuity was analyzed using a longitudinal mixed regression model adjusting for baseline visual acuity.Unit of measure is based on the E-ETDRS visual acuity letter score scale, 0-97, where 0 = worst and 97 = best.

Visual Acuity Better Than 20/40 and no Vitrectomy Prior to the Visit4, 8 and 12 weeks
Ability to Complete Panretinal Photocoagulation (PRP) in the Absence of Vitrectomywithin 112 days of randomization

The proportion of eyes with "complete" panretinal photocoagulation by 16 weeks in abscence of vitrectomy was computed using the life-table method and treatment groups were compared using the log-rank test.

Trial Locations

Locations (66)

Sarasota Retina Institute

🇺🇸

Sarasota, Florida, United States

Retina Consultants of Southwest Florida

🇺🇸

Fort Myers, Florida, United States

Carolina Retina Center

🇺🇸

Columbia, South Carolina, United States

Southeastern Retina Associates, PC

🇺🇸

Kingsport, Tennessee, United States

Georgia Retina, P.C.

🇺🇸

Atlanta, Georgia, United States

Elman Retina Group, P.A.

🇺🇸

Baltimore, Maryland, United States

Case Western Reserve University

🇺🇸

Cleveland, Ohio, United States

University of Washington Medical Center

🇺🇸

Seattle, Washington, United States

Sabates Eye Centers Research Division

🇺🇸

Leawood, Kansas, United States

Southern California Desert Retina Consultants, MC

🇺🇸

Palm Springs, California, United States

Southeast Retina Center, P.C.

🇺🇸

Augusta, Georgia, United States

University of Illinois at Chicago Medical Center

🇺🇸

Chicago, Illinois, United States

Denver Health Medical Center

🇺🇸

Denver, Colorado, United States

Raj K. Maturi, M.D., P.C.

🇺🇸

Indianapolis, Indiana, United States

Henry Ford Health System, Dept of Ophthalmology and Eye Care Services

🇺🇸

Detroit, Michigan, United States

Retina Center, PA

🇺🇸

Minneapolis, Minnesota, United States

Retina Northwest, PC

🇺🇸

Portland, Oregon, United States

Retina and Vitreous of Texas

🇺🇸

Houston, Texas, United States

Baylor Eye Physicians and Surgeons

🇺🇸

Houston, Texas, United States

Medical Center Ophthalmology Associates

🇺🇸

San Antonio, Texas, United States

Retinal Consultants of San Antonio

🇺🇸

San Antonio, Texas, United States

Retinal Consultants of AZ

🇺🇸

Phoenix, Arizona, United States

Medical College of Wiconsin

🇺🇸

Milwaukee, Wisconsin, United States

Retina-Vitreous Surgeons of Central New York, PC

🇺🇸

Syracuse, New York, United States

Retinal Consultants of Southern California Medical Group, Inc.

🇺🇸

Westlake Village, California, United States

Bay Area Retina Associates

🇺🇸

Walnut Creek, California, United States

The George Washington University, Department of Ophthalmology

🇺🇸

Washington, District of Columbia, United States

University of Florida College of Med., Department of Ophthalmology

🇺🇸

Jacksonville, Florida, United States

Florida Retina Consultants

🇺🇸

Lakeland, Florida, United States

New England Retina Associates, PC

🇺🇸

Trumbull, Connecticut, United States

Emory Eye Center

🇺🇸

Atlanta, Georgia, United States

Retina Associates of Sarasota

🇺🇸

Venice, Florida, United States

American Eye Institute

🇺🇸

New Albany, Indiana, United States

Wilmer Eye Institute at Johns Hopkins

🇺🇸

Baltimore, Maryland, United States

Retina Consultants of Delmarva, P.A.

🇺🇸

Salisbury, Maryland, United States

Vitreo-Retinal Associates

🇺🇸

Grand Rapids, Michigan, United States

Barnes Retina Institute

🇺🇸

St. Louis, Missouri, United States

Retina Consultants of Western New York

🇺🇸

Orchard Park, New York, United States

The New York Eye and Ear Infirmary/Faculty Eye Practice

🇺🇸

New York, New York, United States

Mount Sinai School of Medicine, Dept. of Ophthalmology

🇺🇸

New York, New York, United States

Eye Care for the Adirondacks

🇺🇸

Plattsburgh, New York, United States

Charlotte Eye Ear Nose and Throat Assoc, PA

🇺🇸

Charlotte, North Carolina, United States

Piedmont Retina Specialists, PA

🇺🇸

Greensboro, North Carolina, United States

Mid-America Retina Consultants, P.A.

🇺🇸

Kansas City, North Carolina, United States

Retina Associates of Cleveland, Inc.

🇺🇸

Beachwood, Ohio, United States

Family Eye Group

🇺🇸

Lancaster, Pennsylvania, United States

Southeastern Retina Associates, P.C.

🇺🇸

Knoxville, Tennessee, United States

West Texas Retina Consultants P.A.

🇺🇸

Abilene, Texas, United States

Texas Retina Associates

🇺🇸

Lubbock, Texas, United States

Valley Retina Institute

🇺🇸

McAllen, Texas, United States

Virginia Retina Center

🇺🇸

Leesburg, Virginia, United States

Loma Linda University Health Care, Dept. of Ophthalmology

🇺🇸

Loma Linda, California, United States

Wolfe Eye Clinic

🇺🇸

West Des Moines, Iowa, United States

Paducah Retinal Center

🇺🇸

Paducah, Kentucky, United States

University of California, Irvine

🇺🇸

Irvine, California, United States

Medical Associates Clinic, P.C.

🇺🇸

Dubuque, Iowa, United States

Retina and Vitreous Associates of Kentucky

🇺🇸

Lexington, Kentucky, United States

Delaware Valley Retina Associates

🇺🇸

Lawrenceville, New Jersey, United States

OSU Eye Physicians and Surgeons, LLC.

🇺🇸

Columbus, Ohio, United States

University of Pennsylvania Scheie Eye Institute

🇺🇸

Philadelphia, Pennsylvania, United States

Joslin Diabetes Center

🇺🇸

Boston, Massachusetts, United States

Retina Associates of Hawaii, Inc.

🇺🇸

Honolulu, Hawaii, United States

Magruder Eye Institute

🇺🇸

Orlando, Florida, United States

University of North Carolina, Dept of Ophthalmology

🇺🇸

Chapel Hill, North Carolina, United States

Wake Forest University Eye Center

🇺🇸

Winston-Salem, North Carolina, United States

Retina Research Center

🇺🇸

Austin, Texas, United States

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