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

NCT02924987 | Unknown Phase 4

• 1 other identifier: Hôpital Maisonneuve-Rosemont
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetic Macular Edema

Outcome Measures

Primary Outcomes (1)

• Macular central subfield thickness in micrometers

  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 Outcomes (3)

• Macular central subfield thickness in micrometers at 12 months measured by optical coherence tomography in micrometers (HRT+OCT Spectralis model, Heidelberg Engineering, Heidelberg, Germany)

  12 months

• Best corrected visual acuity at 12 months measured in letters using ETDRS chart

  12 months

• Best corrected visual acuity at 6 months measured in letters using ETDRS chart

  6 months

Study Arms (1)

Aflibercept injection

OTHER

Not applicable. There will be no randomization nor stratification to any to study arms or groups.

Drug: Aflibercept Injection

Interventions

Aflibercept Injection DRUG

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.

Also known as: Eylea

Aflibercept injection

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maisonneuve-Rosemont Hospital: lead
• Bayer: collaborator

Study Sites (1)

Maisonneuve Rosemont Hospital

Montreal, Quebec, H1T2M4, Canada

RECRUITING

MeSH Terms

Interventions

aflibercept

Study Officials

• Flavio Rezende

  Ciusss de L'Est de l'Île de Montréal

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manon Lambert

CONTACT

514-252-3400; mlambert.hmr@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 12, 2016
• First Posted: October 5, 2016
• Study Start: November 1, 2016
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: March 27, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)