Prospective, Randomized, Multicenter, Open Label, Phase II Study to Access Efficacy and Safety of Lucentis® Monotherapy (Ranibizumab 0.5 mg Intravitreal Injections) Compared With Lucentis® Plus Panretinal Photocoagulation (PRP) and PRP (Monotherapy) in the Treatment of Patients With High Risk Proliferative Diabetic Retinopathy
Overview
- Phase
- Phase 2
- Intervention
- Panretinal Photocoagulation (PRP)
- Conditions
- High Risk Proliferative Diabetic Retinopathy
- Sponsor
- José Cunha-Vaz
- Enrollment
- 54
- Locations
- 7
- Primary Endpoint
- Regression of neovascularization
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The purpose of this trial is to evaluate safety and to compare the efficacy of intravitreous injection of ranibizumab alone (0.5 mg), versus combination of intravitreous injection of ranibizumab (0.5 mg) plus panretinal photocoagulation, versus panretinal photocoagulation alone in the regression of retinal neovascularization in eyes with high-risk proliferative diabetic retinopathy.
Detailed Description
Panretinal photocoagulation can cause regression of retinal neovascularization and reduce the risk of severe vision loss in people with proliferative diabetic retinopathy. However, this destructive treatment may be associated with side effects (such as: pain, transient blurring, loss of peripheral and/or night vision, increased risk of macular edema and central vision loss) and it is not always efficient in the regression of the neovascularization. Vascular endothelial growth factor (VEGF) has been shown to play a role in retinal neovascularization and retinal vascular leakage related with proliferative diabetic retinopathy and diabetic macular edema. Anti-vascular endothelial growth factor treatments have been hypothesized as an alternative adjunctive treatment for the management of retinal neovascularization and macular edema related with diabetic retinopathy. There are a few reports of retinal traction detachment in patients with proliferative diabetic retinopathy and fibrovascular proliferation (although it is not frequent). However, from our clinical experience, we think that the risk of detachment only exists when there is in place a fibrovascular proliferation with retinal traction previous to the injection. We injected ranibizumab prior to surgery in patients with severe proliferative diabetic retinopathy, that were submitted later to a posterior vitrectomy, to reduce neovascularization and minimize the risk of an intraoperatory hemorrhage caused by the manipulation of the fibrovascular membranes. In total, we already injected and submitted to surgery 15 eyes with the above mentioned condition, with excellent results. The results of the first 10 eyes were presented in the congress of the Portuguese Society of Ophthalmology (2008).
Investigators
José Cunha-Vaz
Investigator Coordinator
Association for Innovation and Biomedical Research on Light and Image
Eligibility Criteria
Inclusion Criteria
- •High-risk proliferative diabetic retinopathy (HR-PDR) eyes.
- •Best Corrected-Visual Acuity at baseline \> 20/320 in the study eye.
- •Clear ocular media and adequate pupillary dilatation to permit good quality fundus photography.
- •Intraocular pressure \< 21 mmHg.
- •Type I, or Type II diabetic subjects as defined by the World Health Organization criteria of either gender, and aged ≥ 18 years.
- •Women must be using effective contraception, be post-menopausal for at least 12 months prior to trial entry, or surgically sterile.
- •Ability to provide written informed consent.
- •Ability to return for all trial visits.
Exclusion Criteria
- •Eyes with prior scatter (panretinal) or focal/grid photocoagulation, within the previous 6 months.
- •Fibrovascular proliferation with retinal traction.
- •Other cause of retinal neovascularization (retinal vein occlusion, radiation retinopathy or others).
- •Atrophy/scarring/fibrosis/ hard exudates involving the center of the macula.
- •Subjects who have received yttrium-aluminum-garnet laser, or peripheral retinal cryoablation, or laser retinopexy (for retinal tears only), or focal/grid photocoagulation, within the previous 6 months.
- •Significant media opacities, which might interfere with visual acuity, assessment of toxicity or fundus photography.
- •Subjects should not be entered if there is likelihood that they will require cataract surgery within the following 1 year.
- •Any intraocular surgery within 6 months before trial enrollment.
- •Previous vitrectomy.
- •HbA1C level \>11% or recent signs of uncontrolled diabetes.
Arms & Interventions
Panretinal Photocoagulation (PRP)
Group 1: Panretinal photocoagulation treatment (PRP) at month-0 that can be repeated after month-3.
Intervention: Panretinal Photocoagulation (PRP)
Ranibizumab
Group 2: Intravitreous injections of ranibizumab every 4 weeks at month-0, month-1 and month-2 that can be repeated after month-3.
Intervention: Intravitreous injection of ranibizumab
Ranibizumab + Panretinal Photocoagulation (PRP)
Group 3: Combination treatment of ranibizumab intravitreous injections plus PRP (2 weeks +/- 1 week after injection), at month-0, month-1 and month-2 that can be repeated after month-3.
Intervention: Panretinal Photocoagulation (PRP)
Ranibizumab + Panretinal Photocoagulation (PRP)
Group 3: Combination treatment of ranibizumab intravitreous injections plus PRP (2 weeks +/- 1 week after injection), at month-0, month-1 and month-2 that can be repeated after month-3.
Intervention: Intravitreous injection of ranibizumab
Outcomes
Primary Outcomes
Regression of neovascularization
Time Frame: 12-month treatment
To demonstrate superiority of one of the treatment arms: ranibizumab 0.5 mg monotherapy, panretinal photocoagulation monotherapy or combination therapy (ranibizumab 0.5 mg plus panretinal photocoagulation) over a 12-month treatment period in the regression of neovascularization.
Secondary Outcomes
- Changes from baseline in Best-Corrected Visual Acuity(12-month treatment)
- Additional focal or grid laser for Diabetic Macular Edema(12 month treatment)
- Need for vitrectomy due to occurrence of vitreous hemorrhage or retinal detachment relative to the three treatment arms.(12-month treatment)
- Changes from baseline in macular retinal thickness by Optical Coherent Tomography(12-month treatment)
- Adverse events(12-month treatment)
- Recurrence of neovascularization(12-month treatment)
- Number of treatments needed(12-month treatment)