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

  Show 67 Study Locations
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:
Hemorrhage
Retinal Diseases
Diabetic Retinopathy
Vitreous Hemorrhage
Pathologic Processes
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Eye Hemorrhage

ClinicalTrials.gov processed this record on September 15, 2014