Clinical trial NCT00996437: Intravitreal Ranibizumab for Vitreous Hemorrhage Due to Proliferative Diabetic Retinopathy (N)
Official title: An Evaluation of Intravitreal Ranibizumab for Vitreous Hemorrhage Due to Proliferative Diabetic Retinopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Vitreous Hemorrhage
Proliferative Diabetic Retinopathy
Keywords: vitreous
hemorrhage
proliferative
diabetic
retinopathy
intravitreal
ranibizumab
Lucentis
saline
vitrectomy
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: National Eye Institute (NEI)
First posted: 2009-10-16
Enrollment: 261
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Treatment or "Failure" Defined as Vitrectomy
timeFrame: within 112 days of randomization
measure: Safety (Injected-related, Ocular Drug-related and Systemic Drug-related)
timeFrame: Baseline to 16 weeks
Secondary outcomes:
measure: Ability to Complete Panretinal Photocoagulation (PRP) in the Absence of Vitrectomy
timeFrame: within 112 days of randomization
measure: Extent of Vitreous Hemorrhage Measured by Optical Coherence Tomography Signal Strength
timeFrame: 4, 8 and 12 weeks
measure: Visual Acuity Adjusted for the Baseline Acuity Regardless of Vitrectomy Status
timeFrame: 4, 8 and 12 weeks
measure: Visual Acuity Better Than 20/40 and no Vitrectomy Prior to the Visit
timeFrame: 4, 8 and 12 weeks
measure: Severe Visual Acuity Loss (Defined as <20/200)
timeFrame: 4,8 and 12 weeks
measure: Very Severe Visual Acuity Loss (Defined as <20/800)
timeFrame: 4,8 and 12 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Retinal Consultants of AZ
state: Arizona
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Health Care, Dept. of Ophthalmology
state: California
city: Palm Springs
country: United States
facility: Southern California Desert Retina Consultants, MC
state: California
city: Walnut Creek
country: United States
facility: Bay Area Retina Associates
state: California
city: Westlake Village
country: United States
facility: Retinal Consultants of Southern California Medical Group, Inc.
state: California
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
city: Trumbull
country: United States
facility: New England Retina Associates, PC
state: Connecticut
city: Washington
country: United States
facility: The George Washington University, Department of Ophthalmology
state: District of Columbia
city: Fort Myers
country: United States
facility: Retina Consultants of Southwest Florida
state: Florida
city: Jacksonville
country: United States
facility: University of Florida College of Med., Department of Ophthalmology
state: Florida
city: Lakeland
country: United States
facility: Florida Retina Consultants
state: Florida
city: Orlando
country: United States
facility: Magruder Eye Institute
state: Florida
city: Sarasota
country: United States
facility: Sarasota Retina Institute
state: Florida
city: Venice
country: United States
facility: Retina Associates of Sarasota
state: Florida
city: Atlanta
country: United States
facility: Emory Eye Center
state: Georgia
city: Atlanta
country: United States
facility: Georgia Retina, P.C.
state: Georgia
city: Augusta
country: United States
facility: Southeast Retina Center, P.C.
state: Georgia
city: Honolulu
country: United States
facility: Retina Associates of Hawaii, Inc.
state: Hawaii
city: Chicago
country: United States
facility: University of Illinois at Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Raj K. Maturi, M.D., P.C.
state: Indiana
city: New Albany
country: United States
facility: American Eye Institute
state: Indiana
city: Dubuque
country: United States
facility: Medical Associates Clinic, P.C.
state: Iowa
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Leawood
country: United States
facility: Sabates Eye Centers Research Division
state: Kansas
city: Lexington
country: United States
facility: Retina and Vitreous Associates of Kentucky
state: Kentucky
city: Paducah
country: United States
facility: Paducah Retinal Center
state: Kentucky
city: Baltimore
country: United States
facility: Elman Retina Group, P.A.
state: Maryland
city: Baltimore
country: United States
facility: Wilmer Eye Institute at Johns Hopkins
state: Maryland
city: Baltimore
country: United States
facility: Wilmer Eye Institute at Johns Hopkins
state: Maryland
city: Salisbury
country: United States
facility: Retina Consultants of Delmarva, P.A.
state: Maryland
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
state: Michigan
city: Grand Rapids
country: United States
facility: Vitreo-Retinal Associates
state: Michigan
city: Minneapolis
country: United States
facility: Retina Center, PA
state: Minnesota
city: St. Louis
country: United States
facility: Barnes Retina Institute
state: Missouri
city: Lawrenceville
country: United States
facility: Delaware Valley Retina Associates
state: New Jersey
city: New York
country: United States
facility: The New York Eye and Ear Infirmary/Faculty Eye Practice
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine, Dept. of Ophthalmology
state: New York
city: Orchard Park
country: United States
facility: Retina Consultants of Western New York
state: New York
city: Plattsburgh
country: United States
facility: Eye Care for the Adirondacks
state: New York
city: Syracuse
country: United States
facility: Retina-Vitreous Surgeons of Central New York, PC
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina, Dept of Ophthalmology
state: North Carolina
city: Charlotte
country: United States
facility: Charlotte Eye Ear Nose and Throat Assoc, PA
state: North Carolina
city: Greensboro
country: United States
facility: Piedmont Retina Specialists, PA
state: North Carolina
city: Kansas City
country: United States
facility: Mid-America Retina Consultants, P.A.
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Eye Center
state: North Carolina
city: Beachwood
country: United States
facility: Retina Associates of Cleveland, Inc.
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: OSU Eye Physicians and Surgeons, LLC.
state: Ohio
city: Portland
country: United States
facility: Retina Northwest, PC
state: Oregon
city: Lancaster
country: United States
facility: Family Eye Group
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Scheie Eye Institute
state: Pennsylvania
city: Columbia
country: United States
facility: Carolina Retina Center
state: South Carolina
city: Kingsport
country: United States
facility: Southeastern Retina Associates, PC
state: Tennessee
city: Knoxville
country: United States
facility: Southeastern Retina Associates, P.C.
state: Tennessee
city: Abilene
country: United States
facility: West Texas Retina Consultants P.A.
state: Texas
city: Austin
country: United States
facility: Retina Research Center
state: Texas
city: Houston
country: United States
facility: Retina and Vitreous of Texas
state: Texas
city: Houston
country: United States
facility: Baylor Eye Physicians and Surgeons
state: Texas
city: Lubbock
country: United States
facility: Texas Retina Associates
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: San Antonio
country: United States
facility: Retinal Consultants of San Antonio
state: Texas
city: Leesburg
country: United States
facility: Virginia Retina Center
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wiconsin
state: Wisconsin
Study officials:
affiliation: Jaeb Center for Health Research
name: Adam R. Glassman, MS
role: STUDY_DIRECTOR
affiliation: Retina Center, PA
name: Abdhish Bhavsar, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.