Proliferative Diabetic Retinopathy (PDR)
Conditions
Interventions
Trade Name: Eylea
Product Name: Aflibercept
Product Code: EMA/CHMP/299413/2012
Pharmaceutical Form: Solution for injection
INN or Propos
Sponsors
Moorfields Eye Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
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 6/24). Please see section 6.3 Re-screening of patients 4.Visual acuity in fellow eye = 2/60 5.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. However, patients will be offered a choice and can opt for the ‘worse seeing eye’ to be randomised 6.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. 7.Ability to give informed consent 8.Women should use effective contraception, be post-menopausal for at least 12 months prior to trial entry, or surgically sterile Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 110
Exclusion criteria
Exclusion criteria: 1.Co-existent 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 3D OCT-1000 (Topcon) SD-OCT as central subfield thickness of more than 300µm due to the presence of morphological evidence of diffuse or cystoid oedema. The equivalent measurement for Spectralis OCT is 320µm and Cirrus HD-OCT is 300µm. 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. (Previous Iluvien therapy is an exclusion). 11.Panretinal photocoagulation within the last 8 weeks. 12.Aphakia. 13.Uncontrolled glaucoma as per investigator’s judgement. 14.Severe external ocular infection. Exclusion criteria also apply to systemic conditions as follows: 15.The participant should not have an HbA1c level of more than 12%. Please see section 6.3 Re-screening of patients. 16.The participant should not have a blood pressure of more than 170/110mmHg. Please see section 6.3 Re-screening of patients. 17.A medical condition that, in the opinion of the investigator, would 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 child bearing potential who do not agree to use effective contraception during the study and for at least 3 months after the study has finished. 22.Breast feeding women. 23.Males who do not agree to use an effective form of contraception for the duration of the study and for 3 months after the study has finished. 24.Participation in an investigational trial involving an investigational medicinal product within 30 days of randomisation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate whether mean change in 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.; Secondary Objective: 1.To measure the effect of intravitreal aflibercept therapy, relative to panretinal photocoagulation on additional visual functions and quality of life outcomes including i)Unilateral and Binocular Esterman visual fields defects ii)Binocular visual acuity iii)Low luminance visual acuity iv)Visual acuity outcomes in terms of visual gain or loss v)Contrast sensitivity using Pelli Robson charts vi)Vision-related quality of life measured by VFQ-25 and RetDQoL vii)Diabetic retinopathy treatment satisfaction outcomes (RetTSQ) viii)Generic health-related quality of life using the EQ-5D, ICECAP-A, and CSRI. 2.To estimate incremental cost-effectiveness of intravitreal aflibercept versus standard PRP treatment at 52 weeks. 3.To determine the proportions of naïvePDR and non-naïve PDR eyes in both arms that do not require panretinal photocoagulation through 52 weeks after basic treatment of 3 loading doses of aflibercept or initial completion of PRP. 4.To compare between a ;Primary end point(s): To evaluate whether mean change in 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.;Timepoint(s) of evaluation of this end point: Participants will have visual acuity tests at every visit, but best corrected visual acuity will be assessed at screening, week 12, week 52 and at the point of withdrawal. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.To measure the effect of intravitreal aflibercept therapy, relative to panretinal photocoagulation on additional visual functions and quality of life outcomes including i)Unilateral and Binocular Esterman visual fields defects ii)Binocular visual acuity iii)Low luminance visual acuity iv)Visual acuity outcomes in terms of visual gain or loss v)Contrast sensitivity using Pelli Robson charts vi)Vision-related quality of life measured by VFQ-25 and RetDQoL vii)Diabetic retinopathy treatment satisfaction outcomes (RetTSQ) viii)Generic health-related quality of life using the EQ-5D, ICECAP-A, and CSRI. 2.To estimate incremental cost-effectiveness of intravitreal aflibercept versus standard PRP treatment at 52 weeks. 3.To determine the proportions of naïvePDR and non-naïve PDR eyes in both arms that do not require panretinal photocoagulation through 52 weeks after basic treatment of 3 loading doses of aflibercept or initial completion of PRP. 4.To compare between arms the regression pattern at 12 weeks and the regression and reactivation patterns of retinal neovascularisation at 52 weeks. 5.To compare the proportion of patients with 1-step and 3-step improvement or worsening of diabetic retinopathy between treatment arms at 12 and 52 weeks as per schedule of assessment. 6.To explore the difference in safety profile between intravitreal aflibercept and panretinal photocoagulation at 52 weeks, in terms of proportion of patients developing macular oedema (defined as central subfield thickness of >300µm on 3DOCT-1000 (Topcon) SD-OCT due to clinical evidence of macular oedema) or Spectralis OCT >320µmor Cirrus HD-OCT >300 µm or its equivalent if any other OCT devices are used, any de novo or increase in existing vitreous haemorrhage, de nov | — |
Countries
United Kingdom
Contacts
Public ContactNatasha Ajraam
Moorfields Eye Hospital
Outcome results
None listed