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 not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by Association for Innovation and Biomedical Research on Light and Image
Sponsor:
Information provided by (Responsible Party):
Association for Innovation and Biomedical Research on Light and Image
ClinicalTrials.gov Identifier:
NCT01941329
First received: September 10, 2013
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
High Risk Proliferative Diabetic Retinopathy
Procedure: Panretinal Photocoagulation (PRP)
Drug: Intravitreous injection of ranibizumab
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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)

Resource links provided by NLM:


Further study details as provided by Association for Innovation and Biomedical Research on Light and Image:

Primary Outcome Measures:
  • Regression of neovascularization [ Time Frame: 12-month treatment ] [ Designated as safety issue: No ]
    Defined as any decrease in the area of neovascularization


Secondary Outcome Measures:
  • Changes in Best Corrected Visual Acuity (BCVA) [ Time Frame: 12-Month treatment ] [ Designated as safety issue: No ]
  • Time to complete neovascularization regression [ Time Frame: 12-Month treatment ] [ Designated as safety issue: No ]
  • Recurrence of neovascularization [ Time Frame: 12-Month treatment ] [ Designated as safety issue: No ]
  • Macular retinal thickness [ Time Frame: 12-Month treatment ] [ Designated as safety issue: No ]
  • Need of treatment for Diabetic Macular Edema [ Time Frame: 12-Month treatment ] [ Designated as safety issue: No ]
  • Need of vitrectomy due to the occurrence of vitreous hemorrhage, tractional retinal detachment or other complications of Diabetic Retinopathy. [ Time Frame: 12-Month treatment ] [ Designated as safety issue: Yes ]
  • Adverse events related to the treatments [ Time Frame: 12-Month treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 94
Study Start Date: April 2014
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01941329

Contacts
Contact: José Cunha-Vaz, MD, PhD 00351239480100 4c@aibili.pt

Locations
France
Department of Ophthalmology, University Hospital, CHU Dijon Not yet recruiting
Dijon, France, 21033
Contact: Catherine Creuzot-Garcher, MD, PhD         
Principal Investigator: Catherine Creuzot-Garcher, MD, PhD         
Centre d'Investigation Clinique - Centre National d'Ophtalmologie des Quinze-Vingts Not yet recruiting
Paris, France, 75571
Contact: Sarah Ayello-Scheer, MD         
Principal Investigator: Sarah Ayello-Scheer, MD         
Department of Ophthalmology, Lariboisière Hospital Not yet recruiting
Paris, France, 75475
Contact: Pascale Massin, MD, PhD         
Principal Investigator: Pascale Massin, MD, PhD         
Italy
Department of Ophthalmology, University Vita Salute - Scientific Institute of San Raffael Not yet recruiting
Milan, Italy, 20132
Contact: Francesco Bandello, MD, PhD         
Principal Investigator: Francesco Bandello, MD, PhD         
Centre for Clinical Trials, Department of Ophthalmology, University of Padova Not yet recruiting
Padova, Italy, 35128
Contact: Edoardo Midena, MD, PhD         
Principal Investigator: Edoardo Midena, MD, PhD         
G.B.Bietti Eye Foundation - IRCCS Not yet recruiting
Rome, Italy, 00198
Contact: Monica Varano, MD         
Principal Investigator: Monica Varano, MD         
Portugal
Centre for Clinical Trials - Association for Innovation and Biomedical Research on Light and Image Not yet recruiting
Coimbra, Portugal, 3000-548
Contact: João Figueira, MD         
Principal Investigator: João Figueira, MD         
Espaço Médico de Coimbra Not yet recruiting
Coimbra, Portugal, 3030-163
Contact: Rufino Silva, MD, PhD         
Principal Investigator: Rufino Silva, MD, PhD         
Instituto de Retina de Lisboa Not yet recruiting
Lisboa, Portugal, 1050-085
Contact: João Nascimento, MD         
Principal Investigator: João Nascimento, MD         
United Kingdom
Ophthalmology Clinical Trials Unit Frimley Park Hospital Foundation Trust Not yet recruiting
Frimley, United Kingdom, GU16 7UJ
Contact: Geeta Menon, MD         
Principal Investigator: Geeta Menon, MD         
Clinical Trial Unit, Dep. Ophth., Gloucestershire Hospitals NHS Foundation Trust Not yet recruiting
Gloucestershire, United Kingdom, GL53 7PX
Contact: Peter Scanlon, MD, PhD         
Principal Investigator: Peter Scanlon, MD, PhD         
Laser and Retinal Research Unit, King's Health Partners Not yet recruiting
London, United Kingdom, SE5 9RS
Contact: Sobha Sivaprasad, MD         
Principal Investigator: Sobha Sivaprasad, MD         
Sponsors and Collaborators
Association for Innovation and Biomedical Research on Light and Image
Investigators
Study Chair: José Cunha-Vaz, MD, PhD Association of Innovation and Biomedical Research on Light and Image
  More Information

No publications provided

Responsible Party: Association for Innovation and Biomedical Research on Light and Image
ClinicalTrials.gov Identifier: NCT01941329     History of Changes
Other Study ID Numbers: ECR-RET-2013-05
Study First Received: September 10, 2013
Last Updated: April 9, 2014
Health Authority: Portugal: National Pharmacy and Medicines Institute
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Italy: The Italian Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Association for Innovation and Biomedical Research on Light and Image:
Diabetes
Proliferative Retinopathy
Ranibizumab
Panretinal Photocoagulation

Additional relevant MeSH terms:
Retinal Diseases
Diabetic Retinopathy
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 18, 2014