Bevacizumab Versus Ranibizumab for Diabetic Retinopathy

April 14, 2015 updated by: Ursula Schmidt-Erfurth, M.D.

A Randomized, Double-masked Study With Intraocular Bevacizumab Compared With Intravitreal Ranibizumab in Patients With Persistent Diabetic Macular Edema or Persistent Active Neovascularisation Following Lasercoagulation

Treatment of diabetic macular edema with perifoveal focal/grid laser coagulation was found to be effective saving the visual acuity only in 50% of patients and only 3-14% of treated patients had an improved visual acuity postoperatively. The decent results of lasercoagulation are associated with potential side effects, as focal scotomas, change of color discrimination and development of epiretinal gliosis. The frequency of perifoveal laser treatments is anatomically limited in case of diabetic macular edema: after application of about 350 coagulates there is no possibility to repeat the laser treatment perifoveolar without creating confluent lasercoagulates and causing significant scotomas. In case of persistence of edema in spite of complete perifoveal grid coagulation, no standard therapy exists. Some previous studies investigated the effect of steroids in patients with diabetic macular edema unresponsive to grid laser photocoagulation, but the benefit on the visual acuity was only temporary and the intravitreal application was associated with significant side effects as cataract progression (up to 50%) and ocular hypertension (up to 20%).

In the Diabetic Retinopathy Study the 4-years rate for severe vision loss in patients with high-risk retinopathy was 20.4 %. In cases of proliferative retinopathy, panretinal (scatter) photocoagulation can reduce the risk for development of high-risk retinopathy by 50% over 6 years. When panretinal lasercoagulation is initiated, about 2000 laser spots are equally distributed in all four quadrants. Since panretinal photocoagulation bares risks like loss of field of vision, central vision reduction and loss of colour vision, this treatment can not be continued unlimited.

In cases of persisting neovascularisations in spite of panretinal photocoagulation, no evidence based therapy exists. There is a high risk for intravitreal bleeding, rubeosis, secondary glaucoma with severe vision loss. When fibrovascular proliferation leads to retinal detachment, vitreo-retinal surgery might be indicated.

Now we know that vascular endothelial growth factor (VEGF) is the major angiogenic stimulus responsible for increase of vasopermeability, cellproliferation and angiogenesis in diabetic retinopathy (DRP). Several studies, evaluating VEGF levels in vitreous, have indicated a role for VEGF in diabetic macular edema: vitreous samples of patients with diabetic macular edema contain elevated VEGF concentration and VEGF injected in experimental studies results in breakdown of the blood-retina barrier.

There is increasing evidence for a therapeutic role of anti-VEGF drugs not only in age-related macular degeneration but also in other diseases as in diabetic macular edema. Intravitreal injections have become the most favored treatment procedure for administering anti-VEGF drugs.

The side effects and the decent results of laser treatment on the visual acuity in diabetic macular edema led to studies using anti-VEGF therapy. Unpublished study results on the aptamer pegaptanib (Macugen™) are promising. A study using the antibody fragment Ranibizumab (Lucentis™) in patiens with diabetic macula edema is in progress. Ranibizumab is now approved to be used as an intravitreal injection.

Currently there is one additional anti-VEGF drug already on the market: Bevacizumab (Avastin™), which has approved as intravenous infusion for the treatment of metastatic colo-rectal cancer. Previous studies have shown that systemic use of Bevacizumab (Avastin™) can obtain very promising results on patients with choroidal neovascularisation (CNV) by age-related macular degenetration. This drug, a monoclonal full-length antibody, designed to bind all isoforms of VEGF is a large molecule. But case reports in patients with CNV caused by age-related macular degeneration and with macular edema from central retinal vein occlusion indicate that intravitreally given Bevacizumab (Avastin™) is effective in diseases originating from the choroids and the retina, too. These findings imply a sufficient penetration of the retina by Bevacizumab (Avastin™).

Based on these new findings and the important role of VEGF in diabetic retinopathy, we propose a pilot study for treatment of persistent diabetic macular edema or persisting active neovascularistaions following lasercoagulation with intravitreally administered Bevacizumab (Avastin™) or Ranibizumab (Lucentis™).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Department of Ophthalmology, Medical University of Vienna

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥18 years
  • Patients with type 1 or type 2 diabetes mellitus
  • HbA1C between 6% and 9 %.
  • Patients with persistent diabetic macular edema with center involvement following completed grid lasercoagulation in the study eye
  • Patients with persistent active neovascularisations following completed panretinal lasercoagulation (at least 2000 spots) in the study eye
  • Last perifoveolar laser treatment 3 months before study entry
  • Central macular thickness (macular edema) of at least 300 - 550 microns in the central subfield as measured by OCT
  • Not eligible for any currently approved treatments or experimental protocols
  • Best corrected visual acuity, using ETDRS charts, of 20/25 to 20/200 (Snellen equivalent) in the study eye
  • Patients with decrease in vision in the study eye due to foveal thickening from diabetic macular edema and not to other causes, in the opinion of the investigator

Exclusion Criteria:

  • A condition that would preclude a patient for participation in the study in opinion of investigator, e.g., unstable medical status including glycemic control and blood pressure
  • History of systemic corticosteroids within 3 months prior to randomization or topical, rectal or inhaled corticosteroids in current use more than 3 times per week
  • Panretinal laser photocoagulation within the past 3 months or macular laser photocoagulation within the past 3 months in the study eye
  • Previous treatment with intravitreal or sub-Tenon triamcinolone within the past 3 months in the study eye
  • Previous participation in clinical trial involving anti-angiogenic drugs (pegabtanib sodium, ranibizumab, anecortave acetate, protein kinase C inhibitor, etc.)
  • History of submacular surgery or other surgical intervention for diabetic macular edema except grid lasercoagulation in the study eye
  • Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
Bevacizumab treatment
Drug: bevacizumab
intravitreal application
Active Comparator: B
Ranibizumab treatment
Drug: Ranibizumab
intravitreal application

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To investigate the change in macular edema and the absolute change in visual acuity. To investigate the change of neovascularisation.
Time Frame: 12 Months
12 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ursula Schmidt-Erfurth, M.D.

Investigators

  • Principal Investigator: Ursula Schmidt-Erfurth, MD, Dep. of Ophthalmology, Medical University of Vienna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2008

Primary Completion (Actual)

March 1, 2013

Study Completion (Actual)

April 1, 2013

Study Registration Dates

First Submitted

October 16, 2007

First Submitted That Met QC Criteria

October 16, 2007

First Posted (Estimate)

October 17, 2007

Study Record Updates

Last Update Posted (Estimate)

April 15, 2015

Last Update Submitted That Met QC Criteria

April 14, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 238/2006

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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