Prospective, Randomized, Open Label, Phase II Study to Assess Efficacy and Safety of Macugen® (Pegaptanib 0.3 mg Intravitreal Injections) Plus Panretinal Photocoagulation and PRP (Monotherapy) in the Treatment With High Risk PDR.
|High Risk Proliferative Diabetic Retinopathy Diabetes Mellitus Type I Diabetes Mellitus Type II||Procedure: Panretinal Photocoagulation (PRP) Drug: Intravitreous injection of pegaptanib||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Prospective, Randomized, Open Label, Phase II Study to Assess Efficacy and Safety of Macugen® (Pegaptanib 0.3 mg Intravitreal Injections) Plus Panretinal Photocoagulation (PRP) and PRP (Monotherapy) in the Treatment of Patients With High Risk Proliferative Diabetic Retinopathy (PDR).|
- Regression of retinal neovascularization [ Time Frame: 12-month treatment ]Retinal neovascularization will be measured in disc area units, and progression of neovascularization will be defined as an increasing of 0.5 disc area associated or not with vitreous haemorrhage, and/or pre-retinal haemorrhage, and/or rubeosis, and/or traccional retinal detachment.
- Changes from baseline in Best-Corrected Visual Acuity (BCVA) [ Time Frame: 12-month treatment ]BCVA will be assessed during the trial (Baseline, Month 3,Month 6, Month 12).
- Changes from baseline in macular retinal thickness by Optical Coherent Tomography (OCT) [ Time Frame: 12-month treatment ]OCT will be assessed during the trial (Baseline, Month 3, Month 6, Month 12).
- Changes from baseline in Visual Fields [ Time Frame: 12-month treatment ]Visual Fields will be performed during the trial (Baseline, Month 3, Month 6, Month 12).
- Recurrence of retinal neovascularization [ Time Frame: 12-month treatment ]To assess if there is recurrence of retinal neovascularization.
- Number of treatments needed [ Time Frame: 12-month treatment ]To analyse the number of treatments given to each subject during the 12-month treatment.
- Additional focal or grid laser for DME [ Time Frame: 12-month treatment ]To assess the number of subjects that received additional focal or grid laser for DME.
- Adverse events [ Time Frame: 12-month treatment ]Drug safety profile.
- Need for vitrectomy due to occurrence of vitreous hemorrhage or retinal detachment [ Time Frame: 12-month treatment ]To assess the number of subjects who needed vitrectomy due to occurrence of vitreous hemorrhage or retinal detachment.
|Study Start Date:||March 2010|
|Study Completion Date:||February 2013|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Panretinal Photocoagulation (PRP)
Group 1: Panretinal photocoagulation treatment (PRP) at week-0 that can be repeated every 6 weeks.
Procedure: Panretinal Photocoagulation (PRP)
Panretinal Photocoagulation (PRP)
Experimental: Pegaptanib + Panretinal Photocoagulation (PRP)
Group 2: Combination treatment of pegaptanib intravitreous injections at weeks 0, 6 and 12 that can be repeated every 6 weeks. Plus PRP after first injection (2 weeks +/- 1 week)and that can be repeated every 12 weeks.
Procedure: Panretinal Photocoagulation (PRP)
Panretinal Photocoagulation (PRP)Drug: Intravitreous injection of pegaptanib
Intravitreous injection of pegaptanib
Panretinal photocoagulation (PRP) can cause regression of retinal neovascularization and reduce the risk of severe vision loss in people with proliferative diabetic retinopathy (PDR). However, this destructive treatment may be associated with side effects (e.g. 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 PDR and diabetic macular edema.
Anti-VEGF treatments have been hypothesized as an adjunctive treatment for the management of retinal neovascularization and macular edema related with diabetic retinopathy (DR).
Anti-VEGF agents, such as Macugen®, combined with PRP are expected to control neovascularization without the need for photocoagulation of the posterior pole, around the macula, thus avoiding the major side effects of standard PRP (visual field loss).
A modification of panretinal photocoagulation (PRP) was recently proposed by Madeira et al., (2009) at the 2009 EURETINA Meeting. The described technique involves the progressive application of the DRS photocoagulation rings in a different sequence. First ring: corresponds to the DRS third ring, extruding from the ora serrata to the midperiphery. Second ring: corresponds to DRS second ring, extruding from the midperiphery towards the vortex veins. Third ring: corresponds to DRS first ring, and will only be performed if necessary. This technique resulted in less aggressive visual fields losses by achieving results with only most peripheral photocoagulation. The combination of intravitreal anti-VEGF treatment with pegaptanib, where a series of 3 injections are injected to reverse the neovascularization, while maintaining the macula dry will be completed by the more long term effect of the panretinal photocoagulation. This peripheral photocoagulation proposed is expected to eliminate the chronic VEGF stimulus by eliminating the chronic ischemic factor, while maintaining the visual fields useful for daily activities such as driving, etc.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01281098
|Center for Clinical Trials - Aibili|
|Coimbra, Portugal, 3000-548|