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| Sponsor: | National Eye Institute (NEI) |
|---|---|
| Collaborators: |
Genentech Allergan |
| Information provided by: | National Eye Institute (NEI) |
| ClinicalTrials.gov Identifier: | NCT00445003 |
Purpose
The purpose of the study is to find out if treatment with an intravitreal injection of triamcinolone or an intravitreal injection of ranibizumab can prevent loss of vision caused by panretinal photocoagulation treatment. At the present time, it is not known whether intravitreal steroid or anti-VEGF injections are beneficial in preventing vision loss after PRP treatment. It is possible that one or both of the types of injections will prevent vision loss after PRP treatment. However, it is not known whether the benefits of the injections will outweigh the risks. It is possible that because of side effects, the injections may not be as good as laser alone in treating the diabetic retinopathy.
| Condition | Intervention | Phase |
|---|---|---|
|
Proliferative Diabetic Retinopathy Diabetic Macular Edema |
Drug: Ranibizumab Drug: Triamcinolone Acetonide Behavioral: Sham injection |
Phase III |
| Study Type: | Interventional |
| Study Design: | Treatment, Randomized, Double Blind (Subject, Outcomes Assessor), Active Control, Parallel Assignment, Efficacy Study |
| Official Title: | Intravitreal Ranibizumab or Triamcinolone Acetonide as Adjunctive Treatment to Panretinal Photocoagulation for Proliferative Diabetic Retinopathy |
| Estimated Enrollment: | 381 |
| Study Start Date: | March 2007 |
| Estimated Study Completion Date: | December 2010 |
| Estimated Primary Completion Date: | February 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| 1: Experimental |
Drug: Ranibizumab
Intravitreal injection of 0.5 mg ranibizumab at baseline and 4 weeks
|
| 2: Experimental |
Drug: Triamcinolone Acetonide
Intravitreal injection of 4 mg triamcinolone acetonide at baseline and sham injection at 4 weeks
|
| 3: Active Comparator |
Behavioral: Sham injection
Sham injection at baseline and 4 weeks
|
Proliferative diabetic retinopathy (PDR) is manifested in retinal neovascularization at the disc NVD) or elsewhere (NVE). Vitreous hemorrhage or traction detachment from PDR is a leading cause of severe visual loss and new onset blindness. Without intervention, 60 percent of individuals with diabetic retinopathy will eventually develop proliferative retinopathy, resulting in significant visual loss in nearly fifty percent.
Proliferative diabetic retinopathy is currently treated with scatter (panretinal) laser photocoagulation (PRP) which destroys areas of the retina but preserves central vision. PRP is most effectively seen in a regression of new vessels, stabilization of the neovascularization, and reduced risk of visual loss. However, the treatment is associated with unavoidable side effects including macular edema with transient or permanent central vision loss, diminished vision loss, and night vision loss. The treatment applies laser burns to the peripheral retinal tissue, destroying outer photoreceptors and retinal pigment epithelium of the retina, and is thought to exert its effect by increasing oxygen delivery to the inner retina and decreasing viable hypoxic cells which are producing growth factors such as VEGF. Studies have implicated vascular endothelial growth factor (VEGF) as the substance leading to neovascularization and/or increased vascular permeability. Thus, it is reasonable to expect that inhibition of VEGF could reduce both PDR and transient vision loss from macular edema. There are several anti-VEGF drugs. Ranibizumab is the drug to be evaluated in this trial. In one trial of ranibizumab on DME, ten patients with chronic DME received a series of 0.5mg intraocular injections. The treatments were well tolerated with no ocular or systemic adverse events. Since intraocular injections of ranibizumab significantly reduced foveal thickness and improved visual acuity in all ten patients, there is strong rationale to consider this drug as adjunctive therapy to PRP in a attempt to reduce the acute, transient edema that may occur with PRP.
Similarly, corticosteroids, a class of substances with anti-inflammatory properties, have demonstrated to inhibit the expression of VEGF. Triamcinolone acetonide is often used as a periocular injection for the treatment of cystoid macular edema (CME) secondary to uveitis. Clinically, triamcinolone acetonide is used in the treatment of proliferative vitreoretinopathy and choroidal neovascularization. Studies on patients with proliferative diabetic retinopathy randomly assigned to receive 4mg triamcinolone 10 to 15 days prior to PRP treatment showed a reduction in central macular thickening, and fluorescein leakage was greater in the injection group than in the control group at 9 and 12 months follow up. Mean visual acuity improved by one line in the injection group and worsened by two lines in the control group.
In summary, there is strong rationale that using either intravitreal ranibizumab or intravitreal triamcinolone acetonide as an adjunct to PRP could reduce the magnitude of vision loss.
This study is being conducted to determine whether intravitreal injection of an anti-VEGF drug or an intravitreal injection of a corticosteroid can reduce the occurrence of macular edema and visual acuity impairment following PRP. Subjects will be randomly assigned with equal probability to one of the following three injection groups:
The initial injection (or sham) is given on the day of randomization. Focal (macular) photocoagulation is given 7 to 10 days following the injection. Panretinal (scatter) photocoagulation can be initiated either on the same day as the focal photocoagulation (immediately following the focal photocoagulation) or on a subsequent day but must be initiated within 14 days of the baseline injection. Required follow-up visits occur at 4, 14, 34 and 56 weeks.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
General Inclusion Criteria
To be eligible, the following inclusion criteria must be met:
General Exclusion Criteria
A subject is not eligible if any of the following exclusion criteria are present:
Study Eye Inclusion Criteria The subject must have at least one eye meeting all of the inclusion criteria and none of the exclusion criteria listed below. Subjects may have one or two study eyes. Subjects with two study eyes will be randomly assigned to receive sham injection at baseline and 4 weeks in one eye and either ranibizumab or triamcinolone in the other eye.
Study Eye Exclusion Criteria
The following exclusions apply to the study eye only (i.e., they may be present for the nonstudy eye unless otherwise specified):
Fellow Eye Criteria
The fellow eye must meet the following criteria:
Contacts and Locations
Show 56 Study Locations| Study Chair: | Alexander J. Brucker, M.D. | Scheie Eye Institute |
| Study Chair: | Joseph Googe, Jr., M.D. | Southeastern Retina Associates, P.C. |
More Information
| Responsible Party: | Jaeb Center for Health Research (DRCR.net) ( Roy W. Beck, MD, PhD, Director ) |
| Study ID Numbers: | NEI-134 |
| Study First Received: | March 6, 2007 |
| Last Updated: | September 9, 2009 |
| ClinicalTrials.gov Identifier: | NCT00445003 History of Changes |
| Health Authority: | United States: Institutional Review Board; United States: Food and Drug Administration |
|
Diabetic Retinopathy Diabetic Macular Edema Lucentis Ranibizumab |
Triamcinolone Panretinal Photocoagulation Combination Therapy pdr |
|
Anti-Inflammatory Agents Molecular Mechanisms of Pharmacological Action Immunologic Factors Physiological Effects of Drugs Hormones, Hormone Substitutes, and Hormone Antagonists Edema Hormones Diabetic Angiopathies Triamcinolone hexacetonide Signs and Symptoms Macular Edema Triamcinolone Acetonide Therapeutic Uses Triamcinolone Cardiovascular Diseases |
Diabetes Complications Retinal Diseases Eye Diseases Diabetes Mellitus Vascular Diseases Macular Degeneration Endocrine System Diseases Retinal Degeneration Enzyme Inhibitors Triamcinolone diacetate Immunosuppressive Agents Glucocorticoids Pharmacologic Actions Diabetic Retinopathy |