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Vitreous HemorrhagePhase 2/3NNCT00996437

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

A Phase 2/3 study testing Ranibizumab and Saline in people with Vitreous Hemorrhage and Proliferative Diabetic Retinopathy, run by Jaeb Center for Health Research at 67 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ranibizumab and Saline
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
261 participants
Where
67 sitesUnited States
Study dates
Jun 2010to Jan 2013
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.

Who cannot join

  • 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.
Show all 18Show fewer
  • 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:
  • 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.

Trial locations and contacts

67 sites in 1 country.

67 sites in 1 country

United States67 sites

  • West Texas Retina Consultants P.A.

    Abilene, Texas, 79605

  • Emory Eye Center

    Atlanta, Georgia, 30322

  • Georgia Retina, P.C.

    Atlanta, Georgia, 30342

  • Southeast Retina Center, P.C.

    Augusta, Georgia, 30909

  • Retina Research Center

    Austin, Texas, 78705

  • Elman Retina Group, P.A.

    Baltimore, Maryland, 21237

  • Wilmer Eye Institute at Johns Hopkins

    Baltimore, Maryland, 21287-9177

  • Wilmer Eye Institute at Johns Hopkins

    Baltimore, Maryland, 21287-9277

  • Retina Associates of Cleveland, Inc.

    Beachwood, Ohio, 44122

  • Joslin Diabetes Center

    Boston, Massachusetts, 02215

  • University of North Carolina, Dept of Ophthalmology

    Chapel Hill, North Carolina, 27599-7040

  • Charlotte Eye Ear Nose and Throat Assoc, PA

    Charlotte, North Carolina, 28210

  • University of Illinois at Chicago Medical Center

    Chicago, Illinois, 60612

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Carolina Retina Center

    Columbia, South Carolina, 29223

  • OSU Eye Physicians and Surgeons, LLC.

    Columbus, Ohio, 43212

  • Denver Health Medical Center

    Denver, Colorado, 80204

  • Henry Ford Health System, Dept of Ophthalmology and Eye Care Services

    Detroit, Michigan, 48202

  • Medical Associates Clinic, P.C.

    Dubuque, Iowa, 52002

  • Retina Consultants of Southwest Florida

    Fort Myers, Florida, 33912

  • Vitreo-Retinal Associates

    Grand Rapids, Michigan, 49525

  • Piedmont Retina Specialists, PA

    Greensboro, North Carolina, 27401

  • Retina Associates of Hawaii, Inc.

    Honolulu, Hawaii, 96813

  • Retina and Vitreous of Texas

    Houston, Texas, 77025

  • Baylor Eye Physicians and Surgeons

    Houston, Texas, 77030

  • Raj K. Maturi, M.D., P.C.

    Indianapolis, Indiana, 46290

  • University of California, Irvine

    Irvine, California, 92697

  • University of Florida College of Med., Department of Ophthalmology

    Jacksonville, Florida, 32209

  • Mid-America Retina Consultants, P.A.

    Kansas City, North Carolina, 64111

  • Southeastern Retina Associates, PC

    Kingsport, Tennessee, 37660

  • Southeastern Retina Associates, P.C.

    Knoxville, Tennessee, 37909

  • Florida Retina Consultants

    Lakeland, Florida, 33805

  • Family Eye Group

    Lancaster, Pennsylvania, 17601-2644

  • Delaware Valley Retina Associates

    Lawrenceville, New Jersey, 08648

  • Sabates Eye Centers Research Division

    Leawood, Kansas, 66211

  • Virginia Retina Center

    Leesburg, Virginia, 20176

  • Retina and Vitreous Associates of Kentucky

    Lexington, Kentucky, 40509-1802

  • Loma Linda University Health Care, Dept. of Ophthalmology

    Loma Linda, California, 92354

  • Texas Retina Associates

    Lubbock, Texas, 79424

  • Valley Retina Institute

    McAllen, Texas, 78503

  • Medical College of Wiconsin

    Milwaukee, Wisconsin, 53226

  • Retina Center, PA

    Minneapolis, Minnesota, 55404

  • American Eye Institute

    New Albany, Indiana, 47150

  • The New York Eye and Ear Infirmary/Faculty Eye Practice

    New York, New York, 10003

  • Mount Sinai School of Medicine, Dept. of Ophthalmology

    New York, New York, 10029

  • Retina Consultants of Western New York

    Orchard Park, New York, 14127

  • Magruder Eye Institute

    Orlando, Florida, 32803

  • Paducah Retinal Center

    Paducah, Kentucky, 42001

  • Southern California Desert Retina Consultants, MC

    Palm Springs, California, 92262

  • University of Pennsylvania Scheie Eye Institute

    Philadelphia, Pennsylvania, 19104

  • Retinal Consultants of AZ

    Phoenix, Arizona, 85014

  • Eye Care for the Adirondacks

    Plattsburgh, New York, 12901

  • Retina Northwest, PC

    Portland, Oregon, 97210

  • Retina Consultants of Delmarva, P.A.

    Salisbury, Maryland, 21804

  • Medical Center Ophthalmology Associates

    San Antonio, Texas, 78240

  • Retinal Consultants of San Antonio

    San Antonio, Texas, 78240

  • Sarasota Retina Institute

    Sarasota, Florida, 34239

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • Barnes Retina Institute

    St Louis, Missouri, 63110

  • Retina-Vitreous Surgeons of Central New York, PC

    Syracuse, New York, 13224

  • New England Retina Associates, PC

    Trumbull, Connecticut, 06611

  • Retina Associates of Sarasota

    Venice, Florida, 34285

  • Bay Area Retina Associates

    Walnut Creek, California, 94598

  • The George Washington University, Department of Ophthalmology

    Washington D.C., District of Columbia, 20037

  • Wolfe Eye Clinic

    West Des Moines, Iowa, 50266

  • Retinal Consultants of Southern California Medical Group, Inc.

    Westlake Village, California, 91361

  • Wake Forest University Eye Center

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Ranibizumab, Saline
Keywords
vitreous, hemorrhage, proliferative, diabetic, retinopathy, intravitreal, ranibizumab, Lucentis, saline, vitrectomy
Medical subject headings
Vitreous Hemorrhage, Hemorrhage, Retinal Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RanibizumabDrug

    Also called Lucentis

    Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks

  • SalineDrug

    Saline injection of 0.5mg at baseline, 4 and 8 weeks

Study groups in NCT00996437
Study groupRoleWhat they receive
Saline InjectionPlacebo comparatorSaline injection at baseline, 4 and 8 weeks
Receives: Drug: Saline
RanibizumabActive comparatorIntravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
Receives: Drug: Ranibizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: within 112 days of randomization

  2. Safety (Injected-related, Ocular Drug-related and Systemic Drug-related)

    Measured: Baseline to 16 weeks

Secondary outcomes (6)

  1. 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.

    Measured: within 112 days of randomization

  2. 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.

    Measured: 4, 8 and 12 weeks

  3. 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.

    Measured: 4, 8 and 12 weeks

  4. Visual Acuity Better Than 20/40 and no Vitrectomy Prior to the Visit

    Measured: 4, 8 and 12 weeks

  5. Severe Visual Acuity Loss (Defined as <20/200)

    Measured: 4,8 and 12 weeks

  6. Very Severe Visual Acuity Loss (Defined as <20/800)

    Measured: 4,8 and 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Oct 2009 (estimated)
  2. Study startJun 2010
  3. Primary completionFeb 2012
  4. Study completionJan 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
261 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00996437
Sponsor's protocol ID
NEI-151
Other IDs
U10EY018817-03, U10EY014231-09
Acronym
N
Status last verified
Aug 2016
First submitted
14 Oct 2009
Last updated
26 Aug 2016
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 25010170

  • 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.

    PubMed 23370902

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Ranibizumab and Saline in people with Vitreous Hemorrhage and Proliferative Diabetic Retinopathy, run by Jaeb Center for Health Research at 67 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 67 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 May 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment or "Failure" Defined as Vitrectomy (time frame: within 112 days of randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00996437, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2016.

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