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 study is a prospective, randomized, multicentre, open label study that intents to compare the efficacy and safety of ranibizumab 0.5 mg Intravitreal (ITV) injections plus Panretinal Photocoagulation versus Panretinal Photocoagulation alone in the regression of the neovascularization area in patients with High Risk Proliferative Diabetic Retinopathy over a 12-month treatment period.
One of the major complications of the diabetes mellitus is Diabetic Retinopathy (DR), one of the leading causes of visual impairment in working age in industrialized countries. Longer diabetes duration and poor glycaemic and blood pressure control are strongly associated with Diabetic Retinopathy. The overall prevalence of any form of Diabetic Retinopathy is 34.4% and 6.96% corresponds to Proliferative Diabetic Retinopathy (PDR). Therefore, approximately 93 million people have Diabetic Retinopathy and 17 million of them have Proliferative Diabetic Retinopathy.
It has been shown that treatment with repeated injections of ranibizumab can improve visual acuity in patients with PDR. Further, , the standard PRP treatment of PDR remains unsatisfactory. The knowledge of the mechanisms of this retinal complication is incomplete and, therefore, efforts should be done to understand and characterize patients' eyes response to combined treatments.
Therefore, the purpose of this study is to compare the standard treatment for PDR (i.e. Panretinal Photocoagulation) with Panretinal Photocoagulation treatment combined with ITV injections of ranibizumab since it is expected that anti-vascular endothelial growth factor (VEGF) treatment with ITV injections will increase the rate of success of Panretinal Photocoagulation in regression of neovascularization with improved final visual acuity.
|High Risk Proliferative Diabetic Retinopathy||Procedure: Panretinal Photocoagulation (PRP) Drug: Intravitreous injection of ranibizumab||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||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)|
- Regression of neovascularization [ Time Frame: 12-month treatment ]Defined as any decrease in the area of neovascularization
- Changes in Best Corrected Visual Acuity (BCVA) [ Time Frame: 12-Month treatment ]
- Time to complete neovascularization regression [ Time Frame: 12-Month treatment ]
- Recurrence of neovascularization [ Time Frame: 12-Month treatment ]
- Macular retinal thickness [ Time Frame: 12-Month treatment ]
- Need of treatment for Diabetic Macular Edema [ Time Frame: 12-Month treatment ]
- Need of vitrectomy due to the occurrence of vitreous hemorrhage, tractional retinal detachment or other complications of Diabetic Retinopathy. [ Time Frame: 12-Month treatment ]
- Adverse events related to the treatments [ Time Frame: 12-Month treatment ]
|Actual Study Start Date:||April 2014|
|Estimated Study Completion Date:||July 2017|
|Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
Experimental: Ranimizumab + Panretinal photocoagulation (PRP)
3 Intravitreous injections of ranibizumab combined with standard PRP (2 ± 1 weeks after injection), at month-0, month-1 and month-2 that can be repeated after month-3, with always at least 1 month of interval between injections.
|Procedure: Panretinal Photocoagulation (PRP) Drug: Intravitreous injection of ranibizumab|
Active Comparator: Panretinal photocoagulation (PRP)
Panretinal photocoagulation treatment (PRP) between month-0 and month-2, with 1 mandatory laser session in month-0 and more laser sessions as needed until Month-2 to complete the PRP treatment.
After completing the PRP treatment, PRP sessions can be repeated from Month-3 to Month-11.
|Procedure: Panretinal Photocoagulation (PRP)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01941329
|Department of Ophthalmology, University Hospital, CHU Dijon|
|Dijon, France, 21033|
|Department of Ophthalmology, Lariboisière Hospital|
|Paris, France, 75475|
|Centre d'Investigation Clinique - Centre National d'Ophtalmologie des Quinze-Vingts|
|Paris, France, 75571|
|Department of Ophthalmology, University Vita Salute - Scientific Institute of San Raffael|
|Milan, Italy, 20132|
|Centre for Clinical Trials, Department of Ophthalmology, University of Padova|
|Padova, Italy, 35128|
|G.B.Bietti Eye Foundation - IRCCS|
|Rome, Italy, 00198|
|Centre for Clinical Trials - Association for Innovation and Biomedical Research on Light and Image|
|Coimbra, Portugal, 3000-548|
|Espaço Médico de Coimbra|
|Coimbra, Portugal, 3030-163|
|Instituto de Retina de Lisboa|
|Lisboa, Portugal, 1050-085|
|Serviço de Oftalmologia,Hospital de Vila Franca de Xira|
|Vila Franca de Xira, Portugal, 2600-009|
|Ophthalmology Clinical Trials Unit Frimley Park Hospital Foundation Trust|
|Frimley, United Kingdom, GU16 7UJ|
|Clinical Trial Unit, Dep. Ophth., Gloucestershire Hospitals NHS Foundation Trust|
|Gloucestershire, United Kingdom, GL53 7PX|
|Laser and Retinal Research Unit, King's Health Partners|
|London, United Kingdom, SE5 9RS|
|Study Chair:||José Cunha-Vaz, MD, PhD||Association of Innovation and Biomedical Research on Light and Image|