Plain English Summary
Background and study aims
The most common cause of loss of vision in diabetes is macular oedema. Diabetes can cause a condition called retinopathy where high blood glucose levels cause damage to the tiny blood vessels lining the surface of the back of the retina. This can result in the growth of new, abnormal blood vessels which may leak blood or fluid into the eye. If this happens in the most sensitive region of the retina, the macula, it causes the area to swell (oedema). Over time, this can lead to scarring and loss of vision. Ranibizumab is a drug used to treat diabetic macular oedema. It is given as an injection into the eye. Whilst it can work well, a large number of injections may be needed over a number of years. Ranibizumab works by preventing the growth of abnormal blood vessels. It is thought that macular oedema is mainly caused by changes in the central blood circulation in the retina. However, it is possible that poor circulation in the peripheral areas of the retina (peripheral ischemia) can lead to an increase in vascular endothelial growth factor (VEGF) levels (a protein that stimulates the growth of blood vessels) which may result in the recurrence of macular oedema, at least in a subset of patients. It has only recently become possible to visualize the degree of peripheral ischaemia with an imaging technique called widefield fluorescein angiography (wFFA). It is therefore possible to target the area of ischaemia with a laser that might reduce VEGF levels and stabilize macular oedema, making the treatment more acceptable for patients, more cost effective and lead to better long term visual results. The aim of this study is to compare the treatment of macular oedema and peripheral ischaemia with a combination of ranibizumab and retinal laser treatment with ranibizumab alone.
Who can participate?
Adults with macular oedema caused by diabetic retinopathy.
What does the study involve?
Participants are randomly allocated into one pf two groups. Those in group 1 are treated with
ranibizumab and retinal laser treatment. Those in group 2 are treated only with the ranibizumab. The treatments are assessed in terms of how long it is before each participant needs a repeat ranibizumab injection, number of injections needed in a year and the participants visual acuity (acuteness/clearness of vision) after a year.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
Newcastle upon Tyne Hospitals NHS Trust (UK)
When is the study starting and how long is it expected to run for?
April 2014 to December 2015
Who is funding the study?
Novartis Pharmaceuticals UK Limited
Who is the main contact?
Mr Sean Scott
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
15819
Study information
Scientific title
Randomized trial of widefield guided PRP for diabetic macular oedema (DMO) treated with Ranibizumab.
(Ranibizumab for DMO PRP trial (RDP trial))
Acronym
Study hypothesis
Ranibizumab is licensed for the treatment of diabetic macular oedema. It is given as an injection into the eye. Whilst it can work well a large number of injections may be needed over a number of years. Ranibizumab works by blocking vascular endothelial growth factor (VEGF). The main pathology causing the oedema maybe due to changes in the central retinal circulation but it is possible that peripheral ischaemia, which is a poor circulation in the peripheral areas of the retina, leads to an increase in VEGF levels and so drives the recurrence of macular oedema, at least in a subset of patients. It has only recently become possible to visualize the degree of peripheral ischaemia with widefield fluorescein angiography (wFFA). It is therefore possible to target the area of ischaemia with peripheral laser that might reduce VEGF levels and so help lead to stabilization of the macular oedema and so make the treatment more acceptable for patients, more cost effective and lead to better long term visual results. In this study patients with macular oedema and peripheral retinal ischaemia will be treated with ranibizumab but randomized to additional retinal laser. The main outcomes will be the length of time a patient does not require an injection, after the initial loading phase. Number of injections in a year and the difference in visual acuity at the end of one year.
Ethics approval
13-NE-0197
Study design
Randomised; Interventional; Design type: Not specified, Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a patient information sheet
Condition
Topic: Diabetes, Ophthalmology; Subtopic: Both, Eye (all Subtopics); Disease: Retinopathy, Ophthalmology
Intervention
Ranibizumab and/or laser:
Patients with OCT confirmed DMO and wFFA confirmed peripheral retinal ischaemia will be randomised to PRP + Ranibizumab or Ranibizumab monotherapy as per pre-defined criteria.
Study Entry : Single Randomisation only
Intervention type
Procedure/Surgery
Phase
Drug names
Primary outcome measures
Primary; Timepoint(s): Number of repeat Ranibizumab injections required after the first 6 months up until one year post treatment
Secondary outcome measures
1. Length of treatment free interval
2. Difference in visual acuity at one year
3. Difference in time
Overall trial start date
01/04/2014
Overall trial end date
31/12/2015
Reason abandoned
Eligibility
Participant inclusion criteria
1. Visual acuity 20/30 to 20/300
2. Macular oedema secondary to diabetic retinopathy. (OCT Thickness of >300 micrometres central subfield, on spectral domain OCT (Spectralis OCT Heidelberg engineering)
3. EDTRS grade 53 – 57 up to non high-risk proliferative diabetic retinopathy
4. Peripheral ischaemia seen on wFFA
5. Patient able to give consent and take part in all study procedures
6. In the opinion of the investigator the patient should benefit from treatment
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 70; UK Sample Size: 70
Participant exclusion criteria
1. Visual acuity worse than 20/300
2. Rubeosis
3. Proliferative retinopathy with high risk characteristics
4. Unable to give consent or take part in all study procedures
5. Other conditions that might interfere with the assessment of the eye such as cataract or prevent the macular oedema from settling such as vitreomacular traction, epiretinal membrane, to a degree that would in the opinion of the investigator affect response to treatment; conditions that would prevent the visual acuity improving such as foveal atrophy, uveitis
6. Previous macular laser within 3 months in the study eye
7. Previous peripheral (PRP) laser in the study eye
8. Previous injection therapy within last 4 months (anti VEGF) 6 months (steroid) in the study eye
9. Pregnant
10. Uncontrolled systemic illness that in the opinion of the investigator would preclude involvement
11. Cataract or other intraocular surgery within 3 months
12. Previous vitrectomy
Recruitment start date
01/04/2014
Recruitment end date
31/12/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Newcastle upon Tyne Hospitals NHS Trust
Queen Victoria Road
Newcastle Upon Tyne
NE1 4LP
United Kingdom
Funders
Funder type
Government
Funder name
Novartis Pharmaceuticals UK Limited
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary