- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01941329
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)
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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Dijon, France, 21033
- Department of Ophthalmology, University Hospital, CHU Dijon
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Paris, France, 75475
- Department of Ophthalmology, Lariboisière Hospital
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Paris, France, 75571
- Centre d'Investigation Clinique - Centre National d'Ophtalmologie des Quinze-Vingts
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Milan, Italy, 20132
- Department of Ophthalmology, University Vita Salute - Scientific Institute of San Raffael
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Padova, Italy, 35128
- Centre for Clinical Trials, Department of Ophthalmology, University of Padova
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Rome, Italy, 00198
- G.B.Bietti Eye Foundation - IRCCS
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Coimbra, Portugal, 3030-163
- Espaco Medico de Coimbra
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Coimbra, Portugal, 3000-548
- Centre for Clinical Trials - Association for Innovation and Biomedical Research on Light and Image
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Lisboa, Portugal, 1050-085
- Instituto de Retina de Lisboa
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Vila Franca de Xira, Portugal, 2600-009
- Serviço de Oftalmologia,Hospital de Vila Franca de Xira
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Frimley, United Kingdom, GU16 7UJ
- Ophthalmology Clinical Trials Unit Frimley Park Hospital Foundation Trust
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Gloucestershire, United Kingdom, GL53 7PX
- Clinical Trial Unit, Dep. Ophth., Gloucestershire Hospitals NHS Foundation Trust
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London, United Kingdom, SE5 9RS
- Laser and Retinal Research Unit, King's Health Partners
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Regression of neovascularization
Time Frame: 12-month treatment
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Defined as any decrease in the area of neovascularization
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12-month treatment
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Changes in Best Corrected Visual Acuity (BCVA)
Time Frame: 12-Month treatment
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12-Month treatment
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Time to complete neovascularization regression
Time Frame: 12-Month treatment
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12-Month treatment
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Recurrence of neovascularization
Time Frame: 12-Month treatment
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12-Month treatment
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Macular retinal thickness
Time Frame: 12-Month treatment
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12-Month treatment
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Need of treatment for Diabetic Macular Edema
Time Frame: 12-Month treatment
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12-Month treatment
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Need of vitrectomy due to the occurrence of vitreous hemorrhage, tractional retinal detachment or other complications of Diabetic Retinopathy.
Time Frame: 12-Month treatment
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12-Month treatment
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Adverse events related to the treatments
Time Frame: 12-Month treatment
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12-Month treatment
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Collaborators and Investigators
Collaborators
Investigators
- Study Chair: José Cunha-Vaz, MD, PhD, Association of Innovation and Biomedical Research on Light and Image
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Eye Diseases
- Endocrine System Diseases
- Diabetic Angiopathies
- Diabetes Complications
- Diabetes Mellitus
- Retinal Diseases
- Diabetic Retinopathy
- Physiological Effects of Drugs
- Antineoplastic Agents
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Ranibizumab
Other Study ID Numbers
- ECR-RET-2013-05
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on High Risk Proliferative Diabetic Retinopathy
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Wills EyeMid Atlantic RetinaCompletedProliferative Diabetic Retinopathy - High RiskUnited States
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José Cunha-VazCompletedHigh Risk Proliferative Diabetic RetinopathyPortugal
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University of CataniaUnknownProliferative Diabetic Retinopathy | Non Proliferative Diabetic RetinopathyItaly
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Asociación para Evitar la Ceguera en MéxicoUnknownProliferative Diabetic Retinopathy | Non Proliferative Diabetic RetinopathyMexico
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Association for Innovation and Biomedical Research...CompletedDiabetes Mellitus Type II | Diabetes Mellitus Type I | High Risk Proliferative Diabetic RetinopathyPortugal
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Valo Health, Inc.RecruitingProliferative Diabetic Retinopathy | Non-proliferative Diabetic RetinopathyUnited States
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Asociación para Evitar la Ceguera en MéxicoUnknownNon Proliferative Diabetic Retinopathy. | Proliferative Diabetic Retinopathy.Mexico
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Ocuphire Pharma, Inc.CompletedDiabetic Retinopathy | Diabetic Macular Edema | NPDR - Non Proliferative Diabetic Retinopathy | PDR - Proliferative Diabetic RetinopathyUnited States
-
King Khaled Eye Specialist HospitalCompletedDiabetic Macular Edema | Proliferative Diabetic Retinopathy | Non-proliferative Diabetic RetinopathySaudi Arabia
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Retina Macula InstituteAllerganCompletedDiabetic Macular Edema | Proliferative Diabetic Retinopathy | Non-proliferative Diabetic RetinopathyUnited States
Clinical Trials on Panretinal Photocoagulation (PRP)
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Baqiyatallah Medical Sciences UniversityCompletedDiabetes Mellitus, Type 2Iran, Islamic Republic of
-
Odense University HospitalUniversity of Southern Denmark; Velux FondenCompletedDiabetes | Proliferative Diabetic Retinopathy | PDRDenmark
-
Hermann Eye CenterEyetech PharmaceuticalsCompletedDiabetic Retinopathy | Iris NeovascularizationUnited States
-
Association for Innovation and Biomedical Research...CompletedDiabetes Mellitus Type II | Diabetes Mellitus Type I | High Risk Proliferative Diabetic RetinopathyPortugal
-
Novartis PharmaceuticalsActive, not recruitingProliferative Diabetic RetinopathyChina, India, Japan, Russian Federation, Turkey, Canada, United States, Australia, Korea, Republic of, Brazil, Philippines, Puerto Rico, Taiwan, Argentina, Chile, Mexico
-
Centre Hospitalier Universitaire DijonRecruiting
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University of Sao Paulo General HospitalConselho Nacional de Desenvolvimento Científico e TecnológicoCompletedDiabetic Retinopathy
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Federal University of São PauloUnknown
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Odense University HospitalMoorfields Eye Hospital NHS Foundation Trust; University of Southern Denmark; Yamagata University and other collaboratorsCompletedProliferative Diabetic RetinopathyDenmark
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Instituto do CoracaoCoordenação de Aperfeiçoamento de Pessoal de Nível Superior.UnknownProliferative Diabetic RetinopathyBrazil