Condition category
Eye Diseases
Date applied
27/06/2019
Date assigned
27/08/2019
Last edited
27/08/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Regular injections of the drug aflibercept into the eye are the most common treatment option for neovascular (wet) age related macular degeneration (AMD) in the UK. Aflibercept treatment typically begins with three injections given at monthly intervals (loading dose), followed by regular review for up to and often beyond 2 years. It is clear that some patients respond to very well after the first three injections, with the retina being completely “dry” (that is without any retinal fluid in the subfoveal area). If the retina is completely dry, it is unlikely additional treatment can improve the visual outcome. In previous studies, it was suggested that these good responders account for about 35-40% of all patients in clinical trials. Recent data suggests that it might be as high as 50% as patients are now presenting earlier to retinal clinics. However, at present, it is impossible to predict the good responders to aflibercept treatment in order to provide patients with better information at the start of treatment. The aim of this study is to use artificial intelligence to evaluate markers of response. The accuracy of artificial intelligence to identify markers of response on optical coherence tomography (OCT) and OCT angiography (OCTA) will be compared to human graders.

Who can participate?
Patients aged 50 to 100 with new onset wet AMD being treated with the loading doses of aflibercept

What does the study involve?
The OCT and OCTA scans done to assess response to aflibercept treatment are collected and analysed by retinal specialists as well as by artificial intelligence.

What are the possible benefits and risks of participating?
The study may not be of benefit to the participant but it will provide better information to retinal specialists for the future management of patients. There is no risk to the participants as these tests are routinely done in the management of patients with AMD having treatment with aflibercept.

Where is the study run from?
Moorfields Eye Hospital (UK)

When is the study starting and how long is it expected to run for?
July 2019 to December 2021

Who is funding the study?
Boehringer Ingelheim

Who is the main contact?
Prof. Sobha Sivaprasad
sobha.sivaprasad@nhs.net

Trial website

Contact information

Type

Scientific

Primary contact

Prof Sobha Sivaprasad

ORCID ID

http://orcid.org/0000-0001-8952-0659

Contact details

NIHR Moorfields Biomedical Research Centre
Moorfields Eye Hospital & UCL Institute of Ophthalmology
162 City Road
London
EC1V 2PD
United Kingdom
+44 (0)7817886759
sobha.sivaprasad@nhs.net

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

SIVS1045

Study information

Scientific title

Can deep phenotyping using retinal images predict response to intravitreal aflibercept therapy in patients with neovascular age-related macular degeneration?

Acronym

PRECISE

Study hypothesis

Can artificial intelligence predict treatment response with aflibercept for neovascular age-related macular degeneration better than human graders?

Ethics approval

Approval pending

Study design

Diagnostic accuracy study

Primary study design

Observational

Secondary study design

Longitudinal study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use contact details to request a patient information sheet

Condition

Wet age-related macular degeneration

Intervention

The OCT and OCTA images taken at baseline and various time points until after the third aflibercept injection for wet AMD will be evaluated by retinal specialists and artificial intelligence to develop a prognostic model to define response to treatment. The total duration of observation is up to 20 weeks post first aflibercept injection.
Duration of follow-up is also up to a maximum of 20 weeks.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Diagnostic accuracy of artificial intelligence over human graders in assessing the response of loading phase of intravitreal aflibercept injections for wet age-related macular degeneration

Secondary outcome measures

1. The analyses will be repeated excluding patients who appeared in the training set and the primary validation set
2. Performance of the AI will be evaluated using higher-quality images with no media opacity (eg, cataracts) as noted by professional graders
3. AUC subgroups will be computed stratified by age and sex, smoking or medical history
4. The analysis will be repeated by calculating the AUC, sensitivity, and specificity of the AI and the proportion of concordant and discordant eyes on the external validation datasets, compared with the reference standards

Overall trial start date

01/07/2019

Overall trial end date

31/12/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Inclusion criteria for both retrospective and prospective parts:
1. Adults who are ≥ 50 years and ≤ 100 years
2. Treatment naïve neovascular AMD at baseline
3. Media clarity, pupillary dilation and patient cooperation for adequate imaging
4. Ability to give informed consent

Inclusion criteria for retrospective part only in addition to the above:
1. Have received 3 loading injections of intravitreal aflibercept therapy at monthly intervals as per standard care
2. Review up to 10 weeks after the 3rd loading dose with or without injection at this visit
3. Had Heidelberg OCT at least at baseline and after the loading phase but ideally 4 Heidelberg OCTs for the 4 visits
4. Heidelberg OCTA images if available for baseline and any visit thereafter (2nd, 3rd or 4th visit) provided there is a baseline OCTA (optional criteria)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

3000

Participant exclusion criteria

1. Co-existent ocular disease: any other ocular condition that, in the opinion of the investigator, might affect or alter visual acuity during the course of the study
2. Any patient who has opted out of their information being used for research nationally or locally at any site

Recruitment start date

01/09/2019

Recruitment end date

01/03/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Moorfields Eye Hospital
162 City Road
London
EC1V 2PD
United Kingdom

Sponsor information

Organisation

Moorfields Eye Hospital

Sponsor details

162 City Road
London
EC1V 2PD
United Kingdom
+44 (0)20 7253 3411 ext 2036
lauren.leitch-devlin@nhs.net

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

Boehringer Ingelheim

Alternative name(s)

Boehringer Ingelheim Pharmaceuticals, Inc., BI

Funding Body Type

private sector organisation

Funding Body Subtype

Trusts, charities, foundations (both publically funded and privately funded)

Location

United States of America

Results and Publications

Publication and dissemination plan

The protocol will be published after ethics approval. Planned publication of the results in a high-impact peer-reviewed journal.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/12/2021

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

08/07/2019: Trial's existence confirmed by funder.