Aflibercept for Retinopathy in the Real World (ARRoW)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Diabetic Retinopathy
• Intervention / Treatment: Other: National Eye Institute Visual Functioning Questionnaire

Detailed Description

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.

• Study Type: Observational

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adults receiving their first ever treatment with aflibercept for diabetic macular oedema

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Timothy Jones
• Collaborators: University Hospitals Bristol and Weston NHS Foundation Trust; Gloucestershire Hospitals NHS Foundation Trust
• Investigators: Principal Investigator: Clare Bailey, MA, BM, BCh(Oxon), MRCP, University Hospitals Bristol and Weston NHS Foundation Trust

Publications and helpful links

General Publications

• Korobelnik JF, Do DV, Schmidt-Erfurth U, Boyer DS, Holz FG, Heier JS, Midena E, Kaiser PK, Terasaki H, Marcus DM, Nguyen QD, Jaffe GJ, Slakter JS, Simader C, Soo Y, Schmelter T, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Zeitz O, Metzig C, Brown DM. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014 Nov;121(11):2247-54. doi: 10.1016/j.ophtha.2014.05.006. Epub 2014 Jul 8.
• Do DV, Nguyen QD, Boyer D, Schmidt-Erfurth U, Brown DM, Vitti R, Berliner AJ, Gao B, Zeitz O, Ruckert R, Schmelter T, Sandbrink R, Heier JS; da Vinci Study Group. One-year outcomes of the da Vinci Study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology. 2012 Aug;119(8):1658-65. doi: 10.1016/j.ophtha.2012.02.010. Epub 2012 Apr 24.
• Diabetic Retinopathy Clinical Research Network; Wells JA, Glassman AR, Ayala AR, Jampol LM, Aiello LP, Antoszyk AN, Arnold-Bush B, Baker CW, Bressler NM, Browning DJ, Elman MJ, Ferris FL, Friedman SM, Melia M, Pieramici DJ, Sun JK, Beck RW. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26;372(13):1193-203. doi: 10.1056/NEJMoa1414264. Epub 2015 Feb 18.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Anticipated): August 1, 2018
• Study Completion (Anticipated): August 1, 2018

Study Registration Dates

• First Submitted: June 22, 2016
• First Submitted That Met QC Criteria: June 22, 2016
• First Posted (Estimate): June 23, 2016

Study Record Updates

• Last Update Posted (Actual): May 4, 2017
• Last Update Submitted That Met QC Criteria: May 2, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Observational Study; Diabetic Retinopathy; aflibercept; Visual Acuity
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Diseases; Diabetic Retinopathy
• Other Study ID Numbers: P201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO