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

NCT ID: NCT00996437

Last Updated: 2016-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 261 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2013-01-31

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.

Conditions

Vitreous Hemorrhage; Proliferative Diabetic Retinopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Saline Injection

Saline injection at baseline, 4 and 8 weeks

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

Saline injection of 0.5mg at baseline, 4 and 8 weeks

Ranibizumab

Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks

Group Type: ACTIVE_COMPARATOR

Ranibizumab

Intervention Type: DRUG

Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks

Interventions

Ranibizumab

Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks

Intervention Type: DRUG

Saline

Saline injection of 0.5mg at baseline, 4 and 8 weeks

Intervention Type: DRUG

Other Intervention Names

Lucentis

Eligibility Criteria

Inclusion Criteria

Age >= 18 years Diagnosis of diabetes mellitus (type 1 or type 2) At least one eye meets the study eye criteria listed below Able and willing to provide informed consent.

Exclusion

A subject can have only one study eye. If both eyes are eligible at the time of randomization, the study eye will be selected by the investigator and subject before randomization.

The eligibility criteria for a study eye are as follows:

Inclusion

Vitreous hemorrhage causing vision impairment, presumed to be from proliferative diabetic retinopathy, and precluding completion of panretinal photocoagulation (or precluding assessment of completeness of prior PRP).

Immediate vitrectomy not required (investigator and subject are willing to wait at least 8 weeks to see if hemorrhage clears sufficiently without having to proceed to vitrectomy).

Visual acuity is light perception or better.

Exclusion

Prompt vitrectomy indicated, such as because of signs of rhegmatogenous retinal detachment or traction detachment involving the macula present on ultrasound.

Exam evidence of neovascular glaucoma, angle neovascularization, or active neovascularization of the iris (small iris tufts not an exclusion).

History of intravitreal anti-VEGF treatment for vitreous hemorrhage at any time in the past or for an indication other than vitreous hemorrhage in the past 2 months.

History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or major ocular surgery other than vitrectomy anticipated within the next 6 months following randomization.

History of vitrectomy. History of yttrium aluminum garnet capsulotomy performed within 2 months prior to randomization.

Aphakia. Uncontrolled glaucoma (in investigator's judgment). Exam evidence of severe external ocular infection, including conjunctivitis, chalazion, or substantial blepharitis.

Exclusion Criteria

A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).

A condition that, in the opinion of the investigator, would preclude subject undergoing elective vitrectomy surgery if indicated during the study.

Participation in an investigational trial that involved treatment with any drug within 30 days of randomization that has not received regulatory approval at the time of study entry.

Known allergy to any component of the study drug. Blood pressure > 180/110 (systolic above 180 or diastolic above 110). Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.

Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization.

For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 4 months.

Subject is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the 12 months of the study.

Study Eye Criteria

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Eye Institute (NEI)

NIH

Sponsor Role: collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adam R. Glassman, MS

Role: STUDY_DIRECTOR

Jaeb Center for Health Research

Abdhish Bhavsar, MD

Role: STUDY_CHAIR

Retina Center, PA

Locations

Retinal Consultants of AZ

Phoenix, Arizona, United States

University of California, Irvine

Irvine, California, United States

Loma Linda University Health Care, Dept. of Ophthalmology

Loma Linda, California, United States

Southern California Desert Retina Consultants, MC

Palm Springs, California, United States

Bay Area Retina Associates

Walnut Creek, California, United States

Retinal Consultants of Southern California Medical Group, Inc.

Westlake Village, California, United States

Denver Health Medical Center

Denver, Colorado, United States

New England Retina Associates, PC

Trumbull, Connecticut, United States

The George Washington University, Department of Ophthalmology

Washington D.C., District of Columbia, United States

Retina Consultants of Southwest Florida

Fort Myers, Florida, United States

University of Florida College of Med., Department of Ophthalmology

Jacksonville, Florida, United States

Florida Retina Consultants

Lakeland, Florida, United States

Magruder Eye Institute

Orlando, Florida, United States

Sarasota Retina Institute

Sarasota, Florida, United States

Retina Associates of Sarasota

Venice, Florida, United States

Emory Eye Center

Atlanta, Georgia, United States

Georgia Retina, P.C.

Atlanta, Georgia, United States

Southeast Retina Center, P.C.

Augusta, Georgia, United States

Retina Associates of Hawaii, Inc.

Honolulu, Hawaii, United States

University of Illinois at Chicago Medical Center

Chicago, Illinois, United States

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

Indianapolis, Indiana, United States

American Eye Institute

New Albany, Indiana, United States

Medical Associates Clinic, P.C.

Dubuque, Iowa, United States

Wolfe Eye Clinic

West Des Moines, Iowa, United States

Sabates Eye Centers Research Division

Leawood, Kansas, United States

Retina and Vitreous Associates of Kentucky

Lexington, Kentucky, United States

Paducah Retinal Center

Paducah, Kentucky, United States

Elman Retina Group, P.A.

Baltimore, Maryland, United States

Wilmer Eye Institute at Johns Hopkins

Baltimore, Maryland, United States

Wilmer Eye Institute at Johns Hopkins

Baltimore, Maryland, United States

Retina Consultants of Delmarva, P.A.

Salisbury, Maryland, United States

Joslin Diabetes Center

Boston, Massachusetts, United States

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

Detroit, Michigan, United States

Vitreo-Retinal Associates

Grand Rapids, Michigan, United States

Retina Center, PA

Minneapolis, Minnesota, United States

Barnes Retina Institute

St Louis, Missouri, United States

Delaware Valley Retina Associates

Lawrenceville, New Jersey, 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

Retina Consultants of Western New York

Orchard Park, New York, United States

Eye Care for the Adirondacks

Plattsburgh, New York, United States

Retina-Vitreous Surgeons of Central New York, PC

Syracuse, New York, United States

University of North Carolina, Dept of Ophthalmology

Chapel Hill, North Carolina, 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

Wake Forest University Eye Center

Winston-Salem, North Carolina, United States

Retina Associates of Cleveland, Inc.

Beachwood, Ohio, United States

Case Western Reserve University

Cleveland, Ohio, United States

OSU Eye Physicians and Surgeons, LLC.

Columbus, Ohio, United States

Retina Northwest, PC

Portland, Oregon, United States

Family Eye Group

Lancaster, Pennsylvania, United States

University of Pennsylvania Scheie Eye Institute

Philadelphia, Pennsylvania, United States

Carolina Retina Center

Columbia, South Carolina, United States

Southeastern Retina Associates, PC

Kingsport, Tennessee, United States

Southeastern Retina Associates, P.C.

Knoxville, Tennessee, United States

West Texas Retina Consultants P.A.

Abilene, Texas, United States

Retina Research Center

Austin, Texas, United States

Retina and Vitreous of Texas

Houston, Texas, United States

Baylor Eye Physicians and Surgeons

Houston, Texas, United States

Texas Retina Associates

Lubbock, Texas, United States

Valley Retina Institute

McAllen, Texas, United States

Medical Center Ophthalmology Associates

San Antonio, Texas, United States

Retinal Consultants of San Antonio

San Antonio, Texas, United States

Virginia Retina Center

Leesburg, Virginia, United States

University of Washington Medical Center

Seattle, Washington, United States

Medical College of Wiconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Bhavsar AR, Torres K, Glassman AR, Jampol LM, Kinyoun JL; Diabetic Retinopathy Clinical Research Network. Evaluation of results 1 year following short-term use of ranibizumab for vitreous hemorrhage due to proliferative diabetic retinopathy. JAMA Ophthalmol. 2014 Jul;132(7):889-90. doi: 10.1001/jamaophthalmol.2014.287. No abstract available.

Reference Type: BACKGROUND

PMID: 25010170 (View on PubMed)

Diabetic Retinopathy Clinical Research Network*. Randomized clinical trial evaluating intravitreal ranibizumab or saline for vitreous hemorrhage from proliferative diabetic retinopathy. JAMA Ophthalmol. 2013 Mar;131(3):283-93. doi: 10.1001/jamaophthalmol.2013.2015.

Reference Type: RESULT

PMID: 23370902 (View on PubMed)

Related Links

http://www.jaeb.org/

Jaeb Center for Health Research

Other Identifiers

U10EY018817-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10EY014231-09

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NEI-151

Identifier Type: -

Identifier Source: org_study_id