Prospective, Randomized, Multicentre, Open-label, Phase II / III Study to Assess Efficacy and Safety of Ranibizumab 0.5 mg Intravitreal Injections Plus Panretinal Photocoagulation (PRP) Versus PRP in Monotherapy in the Treatment of Subjects With High Risk Proliferative Diabetic Retinopathy. (PROTEUS)

This is an interventional treatment trial for High Risk Proliferative Diabetic Retinopathy focused on measuring Diabetes, Proliferative Retinopathy, Ranibizumab, Panretinal Photocoagulation Read More

Inclusion Criteria:

• High-risk proliferative diabetic retinopathy (HR-PDR); Neovascularization in the disc (NVD) ≥ 1/4 disc area (DA) OR Neovascularization elsewhere (NVE) ≥ 1/2 DA; NVE < 1/2 DA + vitreous and/or pre-retinal haemorrhage and/or rubeosis; NVD <1/4 DA + vitreous and/or pre-retinal haemorrhage and/or rubeosis;
• BCVA at baseline ≥ 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters score (approximate Snellen equivalent 20/320);
• Type I or Type II diabetic subjects of either gender;
• Age ≥ 18 years;
• Ability to provide written informed consent;
• Ability to return for all clinical trial visits;

Exclusion Criteria:

• Any intraocular surgery within 6 months before trial enrolment, including:

Prior scatter (panretinal) or focal/grid photocoagulation; Eyes who have received yttrium aluminum garnet (YAG) laser, or peripheral retinal cryoablation, or laser retinopexy (for retinal tears only);

• Fibrovascular proliferation with retinal traction;
• Other cause of retinal NV (retinal vein occlusion, radiation retinopathy or others);
• Atrophy/scarring/fibrosis/ hard exudates involving the centre of the macula;
• Significant media opacities or inadequate pupillary dilation, which might interfere with visual acuity, assessment of toxicity or fundus photography;
• Any likelihood that the subject will require cataract surgery within the following 1 year;
• Diabetic macular edema (DME) with central involvement, i.e., central macular thickness (Central Point Thickness) > 300 µm (Stratus OCT) equivalent values measured by spectral domain (SD)-OCT, adjusted according to the SD-OCT machine used;
• Previous vitrectomy;
• Intraocular pressure > 21 mmHg;
• Previous anti-VEGF therapy within the last 3 months;
• Known serious allergies or history of hypersensitivity to fluorescein used in angiography, or to components of Lucentis® formulation;
• Acute ocular or periocular infection;
• Previous filtering surgery (e.g., trabeculectomy) or placement of a glaucoma drainage device (e.g., tube-shunt surgery); General Exclusion Criteria
• Systolic BP > 170 mmHg or diastolic BP > 100 mmHg;
• HbA1C level >11% or recent signs of uncontrolled diabetes;
• Any of the following underlying systemic diseases:

History or evidence of severe cardiac disease, e.g. New York Heart Association (NYHA) Functional Class III or IV, clinical or medical history of unstable angina, acute coronary syndrome, myocardial infarction, or revascularization procedure within 6 months prior to baseline, or ventricular tachyarrhythmia requiring treatment; History or evidence of clinically significant peripheral vascular disease such as intermittent claudication or prior amputation; Renal failure requiring dialysis or renal transplant or renal insufficiency with creatinine levels > 2.0 mg/dl at screening; Stroke (within 12 months of trial entry); Any major surgical procedure within one month before trial enrolment;

• Subject with a condition (such as advanced, severe or unstable disease or its treatment) or is in a situation which may put him/her at significant risk, which may confound the study results or may interfere significantly with the subject's participation in the study;
• Previous radiation to the head in the region of the study eye;
• Use of any other investigational drugs within the last 3 months (for DR or other condition);
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases;
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation.