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

Proliferative Diabetic Retinopathy Clinical Trial

— N  

Official title:

An Evaluation of Intravitreal Ranibizumab for Vitreous Hemorrhage Due to Proliferative Diabetic Retinopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00996437
• Other study ID #: NEI-151
• Secondary ID: U10EY018817-03U1
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 14, 2009
• Last updated: August 25, 2016
• Start date: June 2010
• Est. completion date: January 2013

Study information

• Verified date: August 2016
• Source: Jaeb Center for Health Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 261
• Est. completion date: January 2013
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Hemorrhage
• Proliferative Diabetic Retinopathy
• Retinal Diseases
• Vitreous Hemorrhage

Intervention

Drug:
• Ranibizumab
Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
• Saline
Saline injection of 0.5mg at baseline, 4 and 8 weeks

Locations

Country	Name	City	State
United States	West Texas Retina Consultants P.A.	Abilene	Texas
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 Research Center	Austin	Texas
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 Associates of Cleveland, Inc.	Beachwood	Ohio
United States	Joslin Diabetes Center	Boston	Massachusetts
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	University of Illinois at Chicago Medical Center	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	Carolina Retina Center	Columbia	South Carolina
United States	OSU Eye Physicians and Surgeons, LLC.	Columbus	Ohio
United States	Denver Health Medical Center	Denver	Colorado
United States	Henry Ford Health System, Dept of Ophthalmology and Eye Care Services	Detroit	Michigan
United States	Medical Associates Clinic, P.C.	Dubuque	Iowa
United States	Retina Consultants of Southwest Florida	Fort Myers	Florida
United States	Vitreo-Retinal Associates	Grand Rapids	Michigan
United States	Piedmont Retina Specialists, PA	Greensboro	North Carolina
United States	Retina Associates of Hawaii, Inc.	Honolulu	Hawaii
United States	Baylor Eye Physicians and Surgeons	Houston	Texas
United States	Retina and Vitreous of Texas	Houston	Texas
United States	Raj K. Maturi, M.D., P.C.	Indianapolis	Indiana
United States	University of California, Irvine	Irvine	California
United States	University of Florida College of Med., Department of Ophthalmology	Jacksonville	Florida
United States	Mid-America Retina Consultants, P.A.	Kansas City	North Carolina
United States	Southeastern Retina Associates, PC	Kingsport	Tennessee
United States	Southeastern Retina Associates, P.C.	Knoxville	Tennessee
United States	Florida Retina Consultants	Lakeland	Florida
United States	Family Eye Group	Lancaster	Pennsylvania
United States	Delaware Valley Retina Associates	Lawrenceville	New Jersey
United States	Sabates Eye Centers Research Division	Leawood	Kansas
United States	Virginia Retina Center	Leesburg	Virginia
United States	Retina and Vitreous Associates of Kentucky	Lexington	Kentucky
United States	Loma Linda University Health Care, Dept. of Ophthalmology	Loma Linda	California
United States	Texas Retina Associates	Lubbock	Texas
United States	Valley Retina Institute	McAllen	Texas
United States	Medical College of Wiconsin	Milwaukee	Wisconsin
United States	Retina Center, PA	Minneapolis	Minnesota
United States	American Eye Institute	New Albany	Indiana
United States	Mount Sinai School of Medicine, Dept. of Ophthalmology	New York	New York
United States	The New York Eye and Ear Infirmary/Faculty Eye Practice	New York	New York
United States	Retina Consultants of Western New York	Orchard Park	New York
United States	Magruder Eye Institute	Orlando	Florida
United States	Paducah Retinal Center	Paducah	Kentucky
United States	Southern California Desert Retina Consultants, MC	Palm Springs	California
United States	University of Pennsylvania Scheie Eye Institute	Philadelphia	Pennsylvania
United States	Retinal Consultants of AZ	Phoenix	Arizona
United States	Eye Care for the Adirondacks	Plattsburgh	New York
United States	Retina Northwest, PC	Portland	Oregon
United States	Retina Consultants of Delmarva, P.A.	Salisbury	Maryland
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	Retinal Consultants of San Antonio	San Antonio	Texas
United States	Sarasota Retina Institute	Sarasota	Florida
United States	University of Washington Medical Center	Seattle	Washington
United States	Barnes Retina Institute	St. Louis	Missouri
United States	Retina-Vitreous Surgeons of Central New York, PC	Syracuse	New York
United States	New England Retina Associates, PC	Trumbull	Connecticut
United States	Retina Associates of Sarasota	Venice	Florida
United States	Bay Area Retina Associates	Walnut Creek	California
United States	The George Washington University, Department of Ophthalmology	Washington	District of Columbia
United States	Wolfe Eye Clinic	West Des Moines	Iowa
United States	Retinal Consultants of Southern California Medical Group, Inc.	Westlake Village	California
United States	Wake Forest University Eye Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Jaeb Center for Health Research	National Eye Institute (NEI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment or "Failure" Defined as Vitrectomy	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.	within 112 days of randomization	No
Primary	Safety (Injected-related, Ocular Drug-related and Systemic Drug-related)		Baseline to 16 weeks	Yes
Secondary	Ability to Complete Panretinal Photocoagulation (PRP) in the Absence of Vitrectomy	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.	within 112 days of randomization	Yes
Secondary	Extent of Vitreous Hemorrhage Measured by Optical Coherence Tomography Signal Strength	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.	4, 8 and 12 weeks	No
Secondary	Visual Acuity Adjusted for the Baseline Acuity Regardless of Vitrectomy Status	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.	4, 8 and 12 weeks	No
Secondary	Visual Acuity Better Than 20/40 and no Vitrectomy Prior to the Visit		4, 8 and 12 weeks	No
Secondary	Severe Visual Acuity Loss (Defined as <20/200)		4,8 and 12 weeks	No
Secondary	Very Severe Visual Acuity Loss (Defined as <20/800)		4,8 and 12 weeks	No

External Links

•   Jaeb Center for Health Research