Lucentis in the Treatment of Macular Edema - A Phase II, Single Center, Randomized Study to Evaluate the Efficacy of Ranibizumab Versus Focal Laser Treatment in Subjects With Diabetic Macular Edema
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Prevention of vision loss at one year as evidenced by ETDRS visual acuity.
研究概览
简要总结
This study will evaluate the clinical efficacy of intra-vitreal injections of Ranibizumab (Lucentis) in the treatment of Diabetic Macular Edema as compared to grid/focal laser.
详细描述
Diabetic macular edema (DME) results from abnormal leakage of macromolecules into the extracellular space from microaneurysms and incompetent blood vessel walls due to small vessel damage from high blood glucose levels. Oncotic forces then allow water into the extracellular space. Abnormalities in the retinal pigment epithelium (RPE) may reduce normal outflow of fluid from the retina to the underlying choriocapillaris via the pump mechanism (Ferris et al. 1984). This leads to retinal edema in the macula with accompanying loss of vision. There is evidence suggesting that vascular endothelial growth factor (VEGF) plays a part in vessel wall permeability with subsequent retinal edema (Aiello et al. 1997).
Studies demonstrate that tight junctions in the vessel walls were shown to be regulated by VEGF and VEGF increases vascular permeability (Anticliff et al. 1999). The healthy human retina contains little or no VEGF. Hypoxia, a component of diabetic retinopathy, causes upregulation of VEGF in the retina (Vinores et al. 1997). Binding VEGF with an antibody specific for VEGF may inhibit resultant edema thus preventing and possibly reversing loss of vision.
Diabetic retinopathy is the leading cause of blindness in people aged 20-74 years, accounting for 8% of all cases of legal blindness and 12% of the newly blind (Klein 1995). A common complication of all forms of diabetes mellitus, diabetic retinopathy is present in over 2.5% of the U.S. population, or more than 5.3 million people aged 18 or older (Prevent Blindness American 2002).
Three forms of retinopathy are commonly recognized in association with all forms of diabetes mellitus: 1) non-proliferative diabetic retinopathy (NPDR), 2) proliferative diabetic retinopathy (PDR), and 3) diabetic macular edema (DME).
NPDR is characterized by ophthalmoscopically visable abnormalities that include microaneurysms, intraretinal hemorrhages, exudates, retina nerve fiber layer infarcts (cotton-wool spots), and, in more severe cases, venous beading and intraretinal microvascular abnormalities (IRMA).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects will be eligible if the following criteria are met:
- •Clinically significant diabetic macular edema (CSME) or clinically significant diabetic macular edema with center involvement (CSME-CI) as defined by the ETDRS Trial (ETDRS Research Group 1987 and 1991)
- •Retinal thickening within 500 mm of the center of the fovea
- •Hard exudates within 500 mm of the center of the fovea (if associated with adjacent retinal thickening, which may be outside of 500um limit)
- •An area of macular edema greater than 1 disc area but within 1 disc diameter of the center of the macula
- •Ability to provide written informed consent and comply with study assessments for the full duration of the study
- •Age > 21 years
- •Visual acuity < 20/320 with definite retinal thickening due to diabetic macular edema based on clinical exam
- •Retinal thickness on OCT measuring 250 microns or more in the central subfield or 350 microns of more in any non-central subfield
- •Media clarity and pupillary dilatation, patient cooperation, and adequate fundus photographs and OCT will be obtainable
- •No other ocular conditions that could cause macular edema will be present
排除标准
- •Subjects who meet any of the following criteria will be excluded from this study:
- •Other causes of macular edema will be present
- •Intraocular pressures exceed 25 mm Hg
- •Prior enrollment in the study
- •Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
- •Participation in another simultaneous medical investigation or trial or previous trial of Lucentis or Avastin
- •Premenopausal women not using adequate contraception The following are considered effective means of contraception: surgical sterilization, use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch
- •Pregnancy or lactation (evidenced by Early Pregnancy Test (EPT) over the counter test)
- •Current treatment of a systemic infection
- •Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders
- •History of recurrent significant infections or bacterial infections
- •Any concurrent intraocular condition in the study eye (e.g., cataract or diabetic retinopathy) that, in the opinion of the investigator, could either
- •Require medical or surgical intervention during the 12-month study period to prevent or treat visual loss that might result from that condition, or
- •If allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of BCVA over the 12-month study period
- •Active intraocular inflammation (grade trace or above) in the study eye
- •Current vitreous hemorrhage in the study eye
- •History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye
- •History of idiopathic or autoimmune-associated uveitis in either eye
- •Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
- •Concurrent ocular disease associated with choroidal neovascularization to include but not limited to presumed ocular Histoplasmosis, high myopia, or macular degeneration
- •Prior/Concomitant Treatment
- •Patient will not have had panretinal photocoagulation treatment within 4 months
- •Grid/focal laser within 2 months of randomization
- •Subtenon steroid in study eye within 6 months
- •Treatment with systemic steroid currently or within the last 4 weeks
- •IVTA within 3 months
- •Previous participation in any studies of investigational drugs within 30 days preceding Day 0 (excluding vitamins and minerals)
- •Prior participation in a Genentech ranibizumab clinical trial
- •Previous treatment with intravitreally (in either eye) or intravenously administered Avastin (bevacizumab)
- •Concurrent use of systemic anti-VEGF agents
- •Previous use of Macugen in study eye
研究组 & 干预措施
I
Lucentis injections for the first three months of the study and then per the protocol for the duration of the trial.
干预措施: Ranibizumab (Lucentis) (Drug)
II
Argon Laser treatment at enrollment and then per the protocol for the duration of the study.
干预措施: Argon Laser (Procedure)
结局指标
主要结局
Prevention of vision loss at one year as evidenced by ETDRS visual acuity.
时间窗: 6 and 12 months
次要结局
- Reduction in retinal thickening based on Optical Coherence Tomography.(6 and 12 months)
研究者
Roy A. Goodart, M.D.
Principal Investigator
Rocky Mountain Retina Consultants