Clinical efficacy and mechanistic evaluation of aflibercept for proliferative diabetic retinopathy

Not Applicable

Completed

• Conditions: Topic: Diabetes, Ophthalmology; Subtopic: Both, Eye (all Subtopics); Disease: Ophthalmology, Other; Eye Diseases

• Registration Number: ISRCTN32207582
• Lead Sponsor: Moorfields Eye Hospital NHS Foundation Trust (UK)

Brief Summary

2015 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/26369798 2017 results in: http://www.ncbi.nlm.nih.gov/pubmed/28494920 2021 results in https://pubmed.ncbi.nlm.nih.gov/33704351/ (added 12/03/2021)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-07-10
• Study Completion: 2015-12-01
• Last Update Posted: 22 March 2021

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

1. Subjects of either sex aged 18 years or over
2. Diagnosis of diabetes mellitus (type 1 or type 2)
3. Best corrected visual acuity in the study eye better than or equal to 54 ETDRS letters (Snellen visual acuity 6/18)
4. PDR with no evidence of previous PRP or presence of new or persistent retinal neovascularisation despite prior PRP that (a) requires treatment in the opinion of the investigator and (b) there is sufficient space in the peripheral retina to perform more PRP treatment. In patients with both eye involvement, the eye with no PRP or the least number of PRP burns will be randomised as the study eye. If both eyes have had no PRP before, the eye with the better visual acuity will be randomised as the study eye
5. Media clarity, pupillary dilation and subject cooperation sufficient for adequate fundus photographs. Eyes with mild pre-retinal haemorrhage or mild vitreous haemorrhage that does not interfere with clear visualisation of the macula and optic disc are eligible for this study
6. Ability to give informed consent
7. Women should use effective contraception, be postmenopausal for at least 12 months prior to trial entry, or be surgically sterile

Exclusion Criteria

The following exclusions apply to the study eye only (i.e. they may be present for the non-study eye):
1. Coexistent ocular disease that will affect visual outcome
2. Moderate or dense vitreous haemorrhage that prevents clear visualisation of the macula and/or optic disc or prevents PRP treatment
3. Significant fibrovascular proliferation or tractional retinal detachment in the posterior pole
4. Prior vitrectomy
5. Presence of macular oedema at baseline confirmed by SDOCT as central subfield thickness of more than 300 µm due to the presence of morphological evidence of diffuse or cystoid oedema. Please see rescreening of patients
6. Other causes of retinal neovascularisation
7. Iris or angle neovascularisation and neovascular glaucoma
8. Anticipated need for cataract extraction or vitrectomy within the next 12 months
9. Known allergy to fluorescein or any components of aflibercept formulation
10. Previous intravitreal anti-VEGF or steroid treatment for diabetic macular oedema in the last 4 months
11. Panretinal photocoagulation within the last 8 weeks
12. Aphakia
13. Uncontrolled glaucoma as per investigator's judgement
14. Severe external ocular infection
15. The participant should not have an HbA1C level of more than 12%.
16.The participant should not have a blood pressure of more than 170/110 mmHg
17. A medical condition that, in the opinion of the investigator, would be preclude participation in the study
18. Myocardial infarction, stroke, transient ischaemic attack, acute congestive cardiac failure or any acute coronary event within 6 months of randomisation
19. Dialysis or renal transplant
20. Pregnant women
21. Women of childbearing potential who do not agree to use effective potential contraception during the study and for at least 3 months after the study has finished. Effective contraception is defined as one of the following:
21.1. Barrier method: condoms or occlusive cap with spermicides
21.2. True abstinence: when it is in line with the preferred and usual lifestyle of subject. Periodic abstinence (e .g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
21.3. Female contraception: have had tubal ligation or bilateral oophorectomy (with or without hysterectomy)
21.4. Male partner sterilisation. The vasectomised male should be the only partner for the female participant.
21.5. Use of established oral, injected or implanted hormonal methods of contraception and intrauterine device.
22. Breastfeeding women
23. Males who do not agree to use an effective form of contraception for the duration of the study and 3 months after the study has finished. Effective contraception is defined as one of the following:
23.1. Barrier method: condoms or occlusive cap with spermicides.
23.2. True abstinence: when in line with preferred and usual lifestyle of the subject. Periodic abstinence and withdrawl are not acceptable methods of contraception
23.3. Male sterilisation (

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate whether best corrected visual acuity following intravitreal aflibercept therapy is non-inferior to panretinal photocoagulation (PRP) in eyes with proliferative diabetic retinopathy (PDR) at 52 weeks as measured by ETDRS letters