Effect of Aflibercept (Eylea®) in the Management of Bevacizumab (Avastin®) Resistant Diabetic Macular Edema (Eylea)

March 23, 2017 updated by: Flavio Rezende, Maisonneuve-Rosemont Hospital

Multicenter randomized trials have demonstrated the safety and efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for the treatment of diabetic macular edema. The results are generally good in the short term, with approximately 75% of patients maintaining or improving vision after initiation of treatment. Despite this favorable outcome, the observation of persistent fluid is not infrequent during treatment, even in patients undergoing monthly treatment sessions. Persistent fluid was observed on optical coherence tomography (OCT) in 70.9% of patients receiving bevacizumab monthly and in 79% of those receiving bevacizumab as needed at the end of the first year in the Comparison of diabetic macular edema. Treatment Trials. It is possible that resolution of this fluid, especially when it is centrally located (i.e., foveal), might result in better visual outcomes.

A drug with higher VEGF-binding affinity may help patients with persistent fluid despite treatment with bevacizumab. Aflibercept is a new intravitreal VEGF antagonist approved on 28 November 2014 by the Health Canada for the treatment of diabetic macular edema.

In contrast to the antibody-based VEGF binding strategy used by bevacizumab, aflibercept incorporates the second binding domain of the VEGFR-1 receptor and the third domain of the VEGFR-2 receptor. By fusing these extracellular protein sequences to the Fc segment of a human IgG backbone, developers have created a chimeric protein with a very high VEGF binding affinity. Aflibercept binds all isomers of the VEGF-A family like bevacizumab, but it also binds VEGF-B and placental growth factors 1 and 2,1,2 which have been both implicated in the pathogenesis of diabetic retinopathy and of age-related macular degeneration. In addition, because of the increased trough binding activity and the stronger binding affinity, aflibercept should be efficacious in neutralizing VEGF more effectively and for longer duration.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

In this study patients recruitment, clinical care and follow-up will be conducted by:

Dr Flavio Rezende: Principal-Investigator and Dr Radwan Ajlan: Co-Investigator.

  1. Purpose: To evaluate the visual acuity outcomes and macular changes at 6 and 12 months of intravitreal aflibercept (2.0 mg) in eyes with persistent center involved diabetic macular edema despite intravitreal bevacizumab therapy.
  2. Overall Goal of Study: The goal of this study is to evaluate the effect of aflibercept on macular edema in patients with diabetic macular edema resistant to bevacizumab.

  3. Specific objectives: To evaluate the visual acuity outcomes and macular changes after 6 and 12 months of intravitreal aflibercept (2.0 mg) in eyes with persistent foveal fluid secondary to diabetic macular edema despite previous optimum gold standard therapy with intravitreal bevacizumab. More specifically, to assess:

    • Mean change in central subfield thickness (CST) from baseline, 6 month after switching to aflibercept.
    • Mean change in CST from baseline, 12 months after switching to aflibercept.
    • Mean change in best corrected visual acuity (BCVA) from baseline, 6 months after switching to aflibercept.
    • Mean change in BCVA from baseline, 12 months after switching to aflibercept
  4. Study Design: Phase 4 open label clinical trial. Intravitreal injection of 0.05 mL (2mg) of aflibercept will be injected. The intravitreal between the first 5 treatments sessions is 4 weeks, and the intravitreal for the following treatment sessions up to week 52 is 8 weeks.
  5. Subjects: 40 patients seen in the retinal clinic of the Hospital Maisonneuve-Rosemont with foveal fluid secondary to diabetic macular edema despite previous optimum gold standard therapy with intravitreal bevacizumab will be assessed for eligibility.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 4

Contacts and Locations

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

Study Contact

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H1T2M4
        • Recruiting
        • Maisonneuve Rosemont Hospital
        • Contact:
        • Principal Investigator:
          • Flavio A Rezende, MD, PhD

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Eyes to be included in the series must have had at least six consecutive monthly intravitreal injections of bevacizumab for the treatment of diabetic macular edema and presented tomographic signals suggestive of foveal fluid on spectral-domain optical coherence tomography (SD-OCT) 4 weeks after the last treatment session. The interval between each of the last 3 consecutive bevacizumab treatments and the interval between the last bevacizumab and the SD-OCT imaging not exceeding 37 days.
  • Persistent foveal fluid is defined as the observation of hypo-reflective spaces on OCT at the fovea (fovea centralis), which measures approximately 1.5 mm (1500 μm) or one disc diameter in size centered at the macular umbo. Tomographic changes will be measured by SD-OCT using the macular thickness maps.
  • BCVA must be better than 20/800. Only 1 eye from each patient will be included in the study. If both eyes are affected, the better seeing eye will be included, since no previous meaningful difference was found in patients with 20/40 or better when treated with bevacizumab or aflibercept.3

Exclusion Criteria:

  • An ocular media opacity that might interfere with visual acuity, assessment of toxicity, or photographic fundus documentation of the macular area.
  • A history of vitrectomy.
  • Known coagulation abnormalities, stroke, or recurrent use of anticoagulative medication other than aspirin.
  • Pregnancy, or planning for pregnancy during the study time frame or the following 3 months.
  • Patients actively undergoing other ocular treatment options such as topical nonsteroidal anti-inflammatory drugs NSAIDs, topical steroids, or intravitreal steroids injections will be excluded from the study.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Aflibercept injection
Not applicable. There will be no randomization nor stratification to any to study arms or groups.
Drug: Aflibercept Injection
Intravitreal injections of 0.05 mL (2mg) of Aflibercept will be injected. The intravitreal between the first 5 treatments sessions is 4 weeks, and the interval for the following treatment sessions up to week 52 is 8 weeks.
Other Names:
  • Eylea

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Macular central subfield thickness in micrometers
Time Frame: 6 Months
Central subfield thickness in micrometers at 6 months measured by optical coherence tomography in micrometers (HRT+OCT Spectralis model, Heidelberg Engineering, Heidelberg, Germany).
6 Months

Secondary Outcome Measures

Outcome Measure
Time Frame
Macular central subfield thickness in micrometers at 12 months measured by optical coherence tomography in micrometers (HRT+OCT Spectralis model, Heidelberg Engineering, Heidelberg, Germany)
Time Frame: 12 months
12 months
Best corrected visual acuity at 12 months measured in letters using ETDRS chart
Time Frame: 12 months
12 months
Best corrected visual acuity at 6 months measured in letters using ETDRS chart
Time Frame: 6 months
6 months

Collaborators and Investigators

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

Sponsor

Maisonneuve-Rosemont Hospital

Collaborators

Bayer

Investigators

  • Principal Investigator: Flavio Rezende, CIUSSS de l'Est de l'Ile de Montréal

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

November 1, 2016

Primary Completion (Anticipated)

November 1, 2017

Study Completion (Anticipated)

November 1, 2017

Study Registration Dates

First Submitted

January 12, 2016

First Submitted That Met QC Criteria

October 3, 2016

First Posted (Estimate)

October 5, 2016

Study Record Updates

Last Update Posted (Actual)

March 27, 2017

Last Update Submitted That Met QC Criteria

March 23, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Hôpital Maisonneuve-Rosemont

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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