Combination OZURDEX® & LUCENTIS® vs. OZURDEX® Monotherapy in Incomplete-Responders With Diabetic Macular Edema: The COLLIDE Trial
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Comparison of mean change from baseline ETDRS BCVA letters
研究概览
简要总结
This is a 24-week, prospective, multi-center, open-label, randomized, investigator-initiated pilot study to explore the effects of RBZ (0.5 mg) plus DEX implant (0.7 mg) PRN combination therapy (n = 30) vs. DEX implant PRN monotherapy (n = 30) in pseudophakic eyes with center-involved DME that have demonstrated prior incomplete response to 3-6 anti-VEGF treatments.
详细描述
- Hypothesis
Pseudophakic center-involved DME eyes with incomplete response to 3-6 anti-VEGF injections (i.e., RBZ, BCZ or IAI) will have similar visual acuity gains, as assessed with AUC analysis (change from baseline randomization (Time 0) BCVA letters through 24 weeks ± 1 week), with a combination treatment regimen consisting of RBZ (0.5 mg) and DEX implant (0.7 mg) vs. a monotherapy treatment regimen with DEX implant (0.7 mg). 2. Description of Study procedures:
Screening (Visit 1): At this initial visit, the study doctor or delegate will explain the study to the patient, answer all of their questions, and will ask them to sign an informed consent form. If the patient agrees to participate in the study, the study doctor or delegate will perform routine examinations; ask them questions about their past medical history, current medical conditions, and all medication or treatments they are receiving. If the patient is female, they may have a urine pregnancy test performed. Patients will undergo your regular eye evaluations. If their glycosylated hemoglobin (HbA1a) level is not available within 12-15 weeks of Visit 1 an HbA1c test will be performed at screening. Patients will be assigned to one of two possible treatment regimens (1.) combination consists of LUCENTIS® (0.5 mg) followed by OZURDEX® (0.7 mg) 0-8 days later or (2.) OZURDEX® (0.7 mg) monotherapy. This visit will last approximately 1-2 hours. Patients will always have the choice of receiving both medications at the same time or split between 2 shorter visits.
Baseline/Randomization (Visit 2): If patients are eligible to receive study treatment(s) they will be scheduled for a baseline randomization study visit to allow collection of eye exam data (intraocular pressure, inflammatory cells, abnormal blood vessels) and ocular coherence tomography OCT. This is the same type of eye exam and OCT patients typically undergo at a retina specialist's office. Additionally, patients will undergo a special vision test and an intravenous fluorescein angiogram to assess retinal circulation. This visit will last approximately 2 hours. The next study visit (Visit 3) will be scheduled in 4-5 weeks. Someone from your study doctor's office will contact the patient prior to the baseline visit to remind you of this next visit
Week 4 (Visit 3): This study visit will allow collection of eye exam data, vision, eye pressure, and OCT. This visit will last approximately 1 hour. The next study visit (Visit 4) will be scheduled in 4-5 weeks. Someone from the study doctor's office will contact the patient prior to the visit to remind them of this next visit.
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
- •Type 1 or 2 diabetic patients
- •Pseudophakic (or phakic without cataract;<1+ nuclear sclerosis) lens status with intact posterior lens capsule and / or Nd:YAG laser capsulotomy that in the investigator's opinion is not likely to permit dislocation of DEX implant into the anterior chamber
- •Center-involved DME > 250 µm
- •Baseline BCVA between 20/40 - 20/320
- •Duration of DME ≤ 9 months
- •Glycosylated haemoglobin (HbA1c) levels ≤ 11%
- •Eyes with intraocular pressure (IOP) ≤ 21 and / or treatment with < 2 topical IOP-lowering medications (eyes with history of previous angle -closure or similar conditions that have been successfully treated with either laser or surgical intervention are allowed as long as the visual fields and optic nerves have been stable for > 1 year prior to study entry and the patient has been and can be safely dilated)
- •Demonstrated incomplete response to 3-6 prior intravitreal anti-VEGFs (AVASTIN®, LUCENTIS®, or EYLEA®; administered every 4 ± 2 weeks over 12-36 weeks (or 3-9 months)); incomplete response is defined herein as a treatment effect resulting in:
- •< 20% reduction in central subfield thickness (CST) by SD-OCT compared to the baseline first RBZ injection, or
- •< 5-letter increase in visual acuity compared to the baseline first RBZ injection and/or
- •the opinion of the treating ophthalmologist additional anti-VEGF monotherapy is not deemed likely to provide further therapeutic benefit
- •If both eyes qualify investigators may enrol bilaterally, with one eye receiving the RBZ plus DEX implant combination regimen and the other receiving the DEX implant monotherapy regimen
- •Written informed patient consent
排除标准
- •Patients with active or suspected ocular or periocular infections including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases.
- •Patients with known hypersensitivity to any components of RBZ or DEX implant
- •Patient has suffered from a stroke or trans-ischemic attack (TIA) in the last 6 months
- •Patients using topical anti-inflammatory medication for the duration of the study
- •Patients with ACIOL (Anterior Chamber Intraocular Lens) and rupture of the posterior lens capsule
- •Prior panretinal or macular laser treatments
- •Previous vitrectomy
- •Any ocular condition that in the opinion of the investigator would not permit improvement of visual acuity with resolution of ME (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates and/or poor foveal architecture suggestive of photoreceptor loss)
- •Patients with retinal diseases, other than diabetes that can affect ME
- •HbA1c levels > 11%
- •Eyes with a history of advanced glaucoma (optic nerve head change consistent with glaucoma damage and / or glaucomatous visual field loss), uncontrolled ocular hypertension (baseline IOP > 21 mmHg despite use of ≥ 2 topical IOP-lowering medication)
- •Eyes with a history of steroid response (i.e., increase of ≥ 5 mmHg IOP following topical steroid treatment)
- •Eyes with demonstrated response to 3-6 prior monotherapy intravitreal anti-VEGF (i.e., AVASTIN®, LUCENTIS® or EYLEA® administered every 4 ± 2 weeks over 12-36 weeks (or 3-9 months)); response is defined herein as a treatment effect resulting in:
- •≥ 20% reduction in CST by SD-OCT from baseline first anti-VEGF injection,
- •≥ 5-letter increase in visual acuity since the baseline first anti-VEGF injection and/or,
- •the opinion of the treating ophthalmologist additional anti-VEGF monotherapy is deemed likely to provide further therapeutic benefit
- •Female patients who are pregnant, breast feeding, or are unable to attend the scheduled follow-up study visits
- •Patients who are unable to attend scheduled follow-up visits throughout the 24-week study
- •Use of systemic steroid, anti-VEGF or pro-VEGF treatment within 4 months prior to enrolment or anticipated use during the study (these drugs are prohibited from use during the study)
研究组 & 干预措施
Combination group (RBZ+DEX)
30 eyes will receive an intravitreal Lucentis (0.5 mg) injection followed by Ozurdex implant (0.7 mg) injection within 0 to 8 days.
干预措施: Ozurdex (Drug)
Combination group (RBZ+DEX)
30 eyes will receive an intravitreal Lucentis (0.5 mg) injection followed by Ozurdex implant (0.7 mg) injection within 0 to 8 days.
干预措施: Lucentis (Drug)
Monotherapy group (DEX only)
30 eyes will receive Ozurdex implant (0.7 mg) injection only
干预措施: Ozurdex (Drug)
结局指标
主要结局
Comparison of mean change from baseline ETDRS BCVA letters
时间窗: From randomization (0) to 24+/- 1 weeks
Carried out using Area Under the Curve (AUC) analysis
次要结局
- Mean change in Central Subfield Thickness (CST)(From randomization (0) to 24+/- 1 weeks)
- Re-injection interval(From randomization (0) to 24+/- 1 weeks)
- Proportion of study eyes with Proliferative Diabetic Retinopathy (PDR) at study completion(From randomization (0) to 24+/- 1 weeks)
- Number of re-injections(From randomization (0) to 24+/- 1 weeks)
- Proportion of eyes with 15- and 10-ETDRS letters gained/lost(From randomization (0) to 24+/- 1 weeks)
研究者
Pradeepa Yoganathan
Principal Investigator
North Toronto Eye Care Laser and Eye Specialists