Early Reperfusion Therapy With Intravenous Thrombolysis for Recovery of VISION in Acute Central Retinal Artery Occlusion
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 127
- 试验地点
- 2
- 主要终点
- Functional recovery at visit 3
研究概览
简要总结
Non-arteritic, thromboembolic central retinal artery occlusion (CRAO) is an acute neurovascular-ophthalmological emergency which leads to severe and permanent vision loss; no evidence-based therapy does exist. Two recent meta-analyses indicate early intravenous thrombolysis to be beneficial in CRAO. Therefore, the REVISION randomized placebo-controlled interventional trial will investigate intravenous alteplase in CRAO as it is practiced in acute ischemic stroke, i.e. within 4.5 hours after symptom onset.
The REVISION observational study will evaluate retinal changes on optical coherence tomography (OCT) in patients within 12 hours of CRAO onset, and the REVISION substudy, which will be conducted adjunct to either the interventional or the observational study, will evaluate the value of the retrobulbar spot sign for prediction of outcome and treatment response.
详细描述
Non-arteritic, thromboembolic central retinal artery occlusion (CRAO) is an acute neurovascular-ophthalmological emergency which leads to severe and permanent vision loss in the affected eye in ~ 95% of cases. Despite a variety of widely practiced "conservative standard treatments", such as hemodilution, ocular massage, and paracentesis, there is no evidence-based therapy for non-arteritic CRAO. Animal models have proven a limited ischemic tolerance of the retina with irreversible damage occurring within only four hours after disruption of blood flow. This is why rapid reperfusion represents THE logical therapeutic approach. Two recent meta-analyses indicate early intravenous thrombolysis to be beneficial in CRAO. Therefore, the REVISION trial will investigate intravenous alteplase in CRAO as it is practiced in acute ischemic stroke, i.e. within 4.5 hours after symptom onset.
Sequential evaluation by optical coherence tomography (OCT) will visualize dynamic ischemic changes of the retina during and after CRAO. The REVISION observational study will enroll patients within 12 hours of symptom onset and aims at comparing late time window retinal findings to early ischemic changes found in patients of the randomized REVISION interventional trial. Ultimately, OCT may become the preferred tool when it comes to assess retinal tissue viability in patients with an unknown CRAO onset (e.g. wake-up CRAO), and CRAO patients who present in an extended time window beyond 4.5 hours.
The REVISION substudy, which will be conducted adjunct to either the interventional or the observational study, will evaluate the value of the retrobulbar spot sign for prediction of outcome and treatment response.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Acute non-arteritic CRAO (i.e. sudden, painless monocular vision loss) ≤ 12 hours after symptom onset confirmed by an experienced ophthalmologist through assessment of: BCVA, intraocular pressure, swinging flash light test (relative afferent pupil defect), slit-lamp biomicroscopy, fundoscopy, and OCT of the macula of both eyes* (*within the 4.5-hour time window: to be skipped if not feasible ≤ 10 minutes; beyond the 4.5-hour time window: mandatory)
- •BCVA of LogMAR ≥ 1.3 in the affected eye (functional blindness according to WHO ICD-11)
- •Reading must have been possible with the affected eye before CRAO (LogMAR ≤ 0.5)
- •Neurological examination performed by an experienced stroke neurologist
- •Brain imaging as per local standard for acute retinal ischemia/stroke assessment, either cranial computed tomography (CT) or cranial magnetic resonance imaging (MRI)
排除标准
- •Suspected giant cell arteritis
- •Other-than-CRAO cause of acute visual loss (e.g., retinal detachment, vitreous hemorrhage, acute glaucoma, acute optic neuritis)
- •BCVA of LogMAR < 1.3 or rapidly improving vision in the affected eye
- •Acute ischemic stroke with indication for on-label intravenous thrombolysis (IVT)
- •Any co-existing or terminal disease with anticipated life expectancy of < 3 months
- •Prior participation in the REVISION trial
研究组 & 干预措施
Thrombolysis (interventional study)
Tenecteplase (0.25 mg per kg body weight as bolus; until trial protocol V04: Alteplase [0.9 mg per kg body weight; 10% as bolus; remaining over one hour] will be administered intravenously within 4.5 hours of symptom onset
干预措施: Tenecteplase (until trial protocol V04: Alteplase) (Drug)
Placebo (interventional study)
Placebo (0.25 mg per kg body weight as bolus; until trial protocol V04: 0.9 mg per kg body weight; 10% as bolus; remaining over one hour) will be administered intravenously within 4.5 hours of symptom onset
干预措施: Tenecteplase (until trial protocol V04: Alteplase) (Drug)
Observational study
The prospective REVISION observational study will enroll patients within 12 hours of symptom onset
结局指标
主要结局
Functional recovery at visit 3
时间窗: 30 days
Functional recovery to best corrected visual acuity of logarithm of the minimum angle of resolution ≤ 0.5 in the affected eye, which corresponds to normal to mild vision impairment (intention-to-treat analysis).
次要结局
- National Institutes of Health Stroke Scale (NIHSS) score at visit 2(72 hours)
- Dichotomized analysis of visual outcome at visits 2, 3, and 4(90 days)
- Central retinal artery recanalization at visits 2, 3, and 4(90 days)
- Visual field at visits 3 and 4(90 days)
- Death at visits 3 and 4(90 days)
- Intraocular hemorrhage in the affected eye at visit 2(72 hours)
- best corrected visual acuity (BCVA) at visits 2, 3, and 4(90 days)
- Retinal arterial perfusion at visits 3 and 4(90 days)
- (Serious) adverse events ((S)AE)(90 days)
- Shift in visual outcome categories at visits 2, 3, and 4(90 days)
- National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) at visits 3 and 4(90 days)
- Fresh ischemic lesions on cranial magnetic resonance imaging (MRI) at visit 2(72 hours)
- Symptomatic intracranial hemorrhage (ICH) until visit 2(72 hours)
- Modified Rankin Scale (mRS) score at visits 3 and 4(90 days)
- Any intracranial hemorrhage (ICH) at visit 2(72 hours)
- Major bleeding until visit 2(72 hours)
- Retinal neovascularization requiring therapy at visit 3 and 4(90 days)