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

Phase 2

Completed

Conditions: Vitreous Hemorrhage
Proliferative Diabetic Retinopathy

Interventions: Drug: Saline
Drug: Ranibizumab

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

Group	Intervention	Description
Saline Injection	Saline	Saline injection at baseline, 4 and 8 weeks
Ranibizumab	Ranibizumab	Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks

Primary Outcome Measures

Name	Time	Method
Treatment or "Failure" Defined as Vitrectomy	within 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

Name	Time	Method
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 Strength	4, 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 Status	4, 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 Visit	4, 8 and 12 weeks
Ability to Complete Panretinal Photocoagulation (PRP) in the Absence of Vitrectomy	within 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): 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, District of Columbia, United States
Retina Consultants of Southwest Florida
🇺🇸
Fort Myers, Florida, United States
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Retinal Consultants of AZ
🇺🇸Phoenix, Arizona, United States