Aflibercept for Retinopathy in the Real World

Study Overview
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Brief Summary
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Diabetic retinopathy remains the leading cause of blindness in patients of working age in the Western World, and there is a global epidemic of diabetes. The recommended treatment for diabetic retinopathy involves injection of anti-vascular endothelial growth factor (anti-VEGF) into the eye. Based on two recent clinical trials taking place in the United States, Europe, Japan, and Australia, NICE issued guidance in July 2015 recommending that aflibercept (a particular type of anti-VEGF treatment) should be available on the NHS for patients in whom the central retina of the eye is at least 400 micrometres thick before treatment. Real-world data can differ significantly from clinical trial data, and it is therefore very important to evaluate the impact of aflibercept in a real world setting, particularly with respect to systemic control, as patients with poor systemic control were excluded from the clinical trials. This study aims to demonstrate the efficacy of aflibercept in a real-world setting, and how this compares to the clinical trial setting.

Detailed Description
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Participants will receive treatment as usual for diabetic macular oedema at Bristol Eye Hospital (University Hospitals Bristol NHS Foundation Trust) and Gloucestershire Hospitals NHS Foundation Trust. This entails injection of aflibercept into the eye, initially with four monthly doses, then as required with regular monthly assessments. Additionally, patients will be invited to complete standardised visual functioning questionnaires at baseline and roughly 6 and 12 months. Patients will be followed up for one year for this study, but treatment will continue as necessary beyond the end of the study. The primary outcome of Best-Corrected Visual Acuity (BCVA) will be assessed at one year and compared to the treatment arm of two recent phase 3 RCTs (VISTA and VIVID). Additional secondary outcomes of retinal thickness, visual functioning, and adverse events will also be collected. Real world data will be collected from Bristol Eye Hospital and Gloucestershire Hospitals NHS Foundation Trust. Bristol Eye Hospital, as part of the RENOIR HIT, has set up a hub and spoke outreach model to treat patients with diabetic macular oedema, and this service has been running since September 2013. Treatment is performed at one of three outreach sites: South Bristol Community hospital, St Georges medical practice in Worle, and a mobile macular unit currently based at Cribbs Causeway. There are about three to five new patients per month commencing treatment with aflibercept in the Bristol area. In Gloucestershire, treatments are performed at Cheltenham General Hospital, and Gloucester Royal Hospital; we expect an additional two to three new patients per month from these sites. All patients attending for routine treatment will be invited to take part in the study. In order to detect a clinically significant difference of 5 letters using the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol, between the real world and the clinical trials, sample size calculations suggest we will need at least 30 new patients to compare to the treatment arm of the clinical trials.

Official Title
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Aflibercept for Retinopathy in the Real World (ARRoW) Study: Evaluation of Anti-VEGF Treatment for Diabetic Macular Oedema

Conditions
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Diabetic Retinopathy

Intervention / Treatment
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* Other: National Eye Institute Visual Functioning Questionnaire


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18+ years Eligible for NHS treatment under the auspices of Bristol Eye Hospital (3 outreach locations) or Gloucestershire NHS Foundation trust. Diagnosis of centre-involving diabetic macular oedema Receiving a first ever treatment of aflibercept in a new eye Exclusion Criteria: Any previous anti-vascular endothelial growth factor (anti-VEGF) treatment in the study eye

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| aflibercept in real world<br>Patients receiving aflibercept for diabetic macular oedema at Bristol Eye Hospital or Gloucestershire Hospitals NHS Foundation Trust | Other: National Eye Institute Visual Functioning Questionnaire<br>* Routine treatment plus visual functioning questionnaires<br>* Other names: NEIVFQ-25;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Best-Corrected Visual Acuity (BCVA) | Best-corrected visual acuity using a standardised measure involving number of Early Treatment Diabetic Retinopathy Study (ETDRS) letters. | Baseline - 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in central retinal thickness | Central retinal thickness measured using optical coherence tomography | Baseline - 12 months | 
| Ocular adverse events | Eye-related adverse events (e.g., endophthalmitis, uveitis, increased intraocular pressure) | 12 months | 
| Non-ocular adverse events | Non-eye-related adverse events (e.g., death, stroke, TIA) | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Observational Study, aflibercept, Diabetic Retinopathy, Visual Acuity