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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Diabetic Retinopathy Clinical Research Network
ClinicalTrials.gov Identifier:
NCT00996437
First received: October 14, 2009
Last updated: May 15, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Vitreous Hemorrhage
Proliferative Diabetic Retinopathy
Drug: Ranibizumab
Drug: Saline
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: An Evaluation of Intravitreal Ranibizumab for Vitreous Hemorrhage Due to Proliferative Diabetic Retinopathy

Resource links provided by NLM:


Further study details as provided by Diabetic Retinopathy Clinical Research Network:

Primary Outcome Measures:
  • Treatment or "Failure" Defined as Vitrectomy [ Time Frame: within 112 days of randomization ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to 16 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Ability to Complete Panretinal Photocoagulation (PRP) in the Absence of Vitrectomy [ Time Frame: within 112 days of randomization ] [ Designated as safety issue: Yes ]
    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.

  • Extent of Vitreous Hemorrhage Measured by Optical Coherence Tomography Signal Strength [ Time Frame: 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
    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 Status [ Time Frame: 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
    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 Visit [ Time Frame: 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
  • Severe Visual Acuity Loss (Defined as <20/200) [ Time Frame: 4,8 and 12 weeks ] [ Designated as safety issue: No ]
  • Very Severe Visual Acuity Loss (Defined as <20/800) [ Time Frame: 4,8 and 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 261
Study Start Date: June 2010
Study Completion Date: January 2013
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Saline Injection
Saline injection at baseline, 4 and 8 weeks
Drug: Saline
Saline injection of 0.5mg at baseline, 4 and 8 weeks
Active Comparator: Ranibizumab
Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
Drug: Ranibizumab
Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
Other Name: Lucentis

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Subject-level Criteria

Inclusion

To be eligible, the following inclusion criteria must be met:

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 is not eligible if any of the following exclusion criteria are present:

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

The subject must have at least one eye meeting all of the inclusion criteria and none of the exclusion criteria listed below.

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00996437

  Hide Study Locations
Locations
United States, Arizona
Retinal Consultants of AZ
Phoenix, Arizona, United States, 85014
United States, California
University of California, Irvine
Irvine, California, United States, 92697
Loma Linda University Health Care, Dept. of Ophthalmology
Loma Linda, California, United States, 92354
Southern California Desert Retina Consultants, MC
Palm Springs, California, United States, 92262
Bay Area Retina Associates
Walnut Creek, California, United States, 94598
Retinal Consultants of Southern California Medical Group, Inc.
Westlake Village, California, United States, 91361
United States, Colorado
Denver Health Medical Center
Denver, Colorado, United States, 80204
United States, Connecticut
New England Retina Associates, PC
Trumbull, Connecticut, United States, 06611
United States, District of Columbia
The George Washington University, Department of Ophthalmology
Washington, District of Columbia, United States, 20037
United States, Florida
Retina Consultants of Southwest Florida
Fort Myers, Florida, United States, 33912
University of Florida College of Med., Department of Ophthalmology
Jacksonville, Florida, United States, 32209
Florida Retina Consultants
Lakeland, Florida, United States, 33805
Magruder Eye Institute
Orlando, Florida, United States, 32803
Sarasota Retina Institute
Sarasota, Florida, United States, 34239
Retina Associates of Sarasota
Venice, Florida, United States, 34285
United States, Georgia
Emory Eye Center
Atlanta, Georgia, United States, 30322
Georgia Retina, P.C.
Atlanta, Georgia, United States, 30342
Southeast Retina Center, P.C.
Augusta, Georgia, United States, 30909
United States, Hawaii
Retina Associates of Hawaii, Inc.
Honolulu, Hawaii, United States, 96813
United States, Illinois
University of Illinois at Chicago Medical Center
Chicago, Illinois, United States, 60612
United States, Indiana
Raj K. Maturi, M.D., P.C.
Indianapolis, Indiana, United States, 46290
American Eye Institute
New Albany, Indiana, United States, 47150
United States, Iowa
Medical Associates Clinic, P.C.
Dubuque, Iowa, United States, 52002
Wolfe Eye Clinic
West Des Moines, Iowa, United States, 50266
United States, Kansas
Sabates Eye Centers Research Division
Leawood, Kansas, United States, 66211
United States, Kentucky
Retina and Vitreous Associates of Kentucky
Lexington, Kentucky, United States, 40509-1802
Paducah Retinal Center
Paducah, Kentucky, United States, 42001
United States, Maryland
Elman Retina Group, P.A.
Baltimore, Maryland, United States, 21237
Wilmer Eye Institute at Johns Hopkins
Baltimore, Maryland, United States, 21287-9177
Wilmer Eye Institute at Johns Hopkins
Baltimore, Maryland, United States, 21287-9277
Retina Consultants of Delmarva, P.A.
Salisbury, Maryland, United States, 21804
United States, Massachusetts
Joslin Diabetes Center
Boston, Massachusetts, United States, 02215
United States, Michigan
Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
Detroit, Michigan, United States, 48202
Vitreo-Retinal Associates
Grand Rapids, Michigan, United States, 49525
United States, Minnesota
Retina Center, PA
Minneapolis, Minnesota, United States, 55404
United States, Missouri
Barnes Retina Institute
St. Louis, Missouri, United States, 63110
United States, New Jersey
Delaware Valley Retina Associates
Lawrenceville, New Jersey, United States, 08648
United States, New York
The New York Eye and Ear Infirmary/Faculty Eye Practice
New York, New York, United States, 10003
Mount Sinai School of Medicine, Dept. of Ophthalmology
New York, New York, United States, 10029
Retina Consultants of Western New York
Orchard Park, New York, United States, 14127
Eye Care for the Adirondacks
Plattsburgh, New York, United States, 12901
Retina-Vitreous Surgeons of Central New York, PC
Syracuse, New York, United States, 13224
United States, North Carolina
University of North Carolina, Dept of Ophthalmology
Chapel Hill, North Carolina, United States, 27599-7040
Charlotte Eye Ear Nose and Throat Assoc, PA
Charlotte, North Carolina, United States, 28210
Piedmont Retina Specialists, PA
Greensboro, North Carolina, United States, 27401
Mid-America Retina Consultants, P.A.
Kansas City, North Carolina, United States, 64111
Wake Forest University Eye Center
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Retina Associates of Cleveland, Inc.
Beachwood, Ohio, United States, 44122
Case Western Reserve University
Cleveland, Ohio, United States, 44106
OSU Eye Physicians and Surgeons, LLC.
Columbus, Ohio, United States, 43212
United States, Oregon
Retina Northwest, PC
Portland, Oregon, United States, 97210
United States, Pennsylvania
Family Eye Group
Lancaster, Pennsylvania, United States, 17601-2644
University of Pennsylvania Scheie Eye Institute
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Carolina Retina Center
Columbia, South Carolina, United States, 29223
United States, Tennessee
Southeastern Retina Associates, PC
Kingsport, Tennessee, United States, 37660
Southeastern Retina Associates, P.C.
Knoxville, Tennessee, United States, 37909
United States, Texas
West Texas Retina Consultants P.A.
Abilene, Texas, United States, 79605
Retina Research Center
Austin, Texas, United States, 78705
Retina and Vitreous of Texas
Houston, Texas, United States, 77025
Baylor Eye Physicians and Surgeons
Houston, Texas, United States, 77030
Texas Retina Associates
Lubbock, Texas, United States, 79424
Valley Retina Institute
McAllen, Texas, United States, 78503
Retinal Consultants of San Antonio
San Antonio, Texas, United States, 78240
Medical Center Ophthalmology Associates
San Antonio, Texas, United States, 78240
United States, Virginia
Virginia Retina Center
Leesburg, Virginia, United States, 20176
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
United States, Wisconsin
Medical College of Wiconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Diabetic Retinopathy Clinical Research Network
Investigators
Study Director: Adam R. Glassman, MS Jaeb Center for Health Research
Study Chair: Abdhish Bhavsar, MD Retina Center, PA
  More Information

Additional Information:
No publications provided by Diabetic Retinopathy Clinical Research Network

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Diabetic Retinopathy Clinical Research Network
ClinicalTrials.gov Identifier: NCT00996437     History of Changes
Other Study ID Numbers: NEI-151, U10EY018817-03, U10EY014231-09
Study First Received: October 14, 2009
Results First Received: February 19, 2013
Last Updated: May 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Diabetic Retinopathy Clinical Research Network:
vitreous
hemorrhage
proliferative
diabetic
retinopathy
intravitreal
ranibizumab
Lucentis
saline
vitrectomy

Additional relevant MeSH terms:
Diabetic Retinopathy
Hemorrhage
Retinal Diseases
Vitreous Hemorrhage
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Pathologic Processes
Eye Hemorrhage

ClinicalTrials.gov processed this record on July 29, 2014