Early Reperfusion Therapy With Intravenous Thrombolysis for Recovery of VISION in Acute Central Retinal Artery Occlusion
- Registration Number
- NCT04965038
- Lead Sponsor
- University Hospital Tuebingen
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 422
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Thrombolysis (interventional study) Alteplase 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 Placebo (interventional study) Alteplase Placebo (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
- Primary Outcome Measures
Name Time Method Functional recovery at visit 3 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).
- Secondary Outcome Measures
Name Time Method National Institutes of Health Stroke Scale (NIHSS) score at visit 2 72 hours NIHSS for assessment of neurological deficits due to ischemic stroke or intracranial hemorrhage
Dichotomized analysis of visual outcome at visits 2, 3, and 4 90 days Dichotomized analysis of visual outcome: 'normal vision to moderate vision impairment' vs. 'severe vision impairment or functional blindness' and 'normal vision to severe vision impairment' vs. 'functional blindness'.
Central retinal artery recanalization at visits 2, 3, and 4 90 days Central retinal artery recanalization assessed using optical coherence tomography angiography (OCTA) of the optic nerve head and the macula.
Visual field at visits 3 and 4 90 days Kinetic visual field using III4e mark
Death at visits 3 and 4 90 days All-cause and stroke-related death
Intraocular hemorrhage in the affected eye at visit 2 72 hours Intraocular hemorrhage in the affected eye
best corrected visual acuity (BCVA) at visits 2, 3, and 4 90 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 and per-protocol analyses).
Retinal arterial perfusion at visits 3 and 4 90 days Retinal arterial perfusion assessed using fluorescein angiography.
(Serious) adverse events ((S)AE) 90 days AE until visit 2, serious AE and AE of special interest until visit 3 and 4
Shift in visual outcome categories at visits 2, 3, and 4 90 days Shift in visual outcome categories: normal vision (logarithm of the minimum angle of resolution (LogMAR) ≤ 0), mild vision impairment (LogMAR \> 0 and ≤ 0.5), moderate vision impairment (LogMAR \> 0.5 and ≤ 1.0), severe vision impairment (LogMAR \> 1.0 and ≤ 1.3), counting fingers (LogMAR \> 1.3 and ≤ counting fingers), hand motion or light perception, and no light perception.
National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) at visits 3 and 4 90 days NEI-VFQ-25 for assessment of relevant visual impairment
Fresh ischemic lesions on cranial magnetic resonance imaging (MRI) at visit 2 72 hours Fraction of patients with and number of acute ischemic lesions on follow-up diffusion-weighted cranial MRI
Symptomatic intracranial hemorrhage (ICH) until visit 2 72 hours Symptomatic ICH (as per ECASS III and Heidelberg bleeding classification) until follow-up magnetic resonance imaging; in case of missing follow-up brain imaging due to premature death, symptomatic ICH will be replaced by "symptomatic ICH or death without repeat scan")
Modified Rankin Scale (mRS) score at visits 3 and 4 90 days Dichotomized analysis and shift analyses of mRS (categories 0 - 1 (excellent outcome) vs. 2 - 6, 0 - 2 (functional independence) vs. 3 - 6, 0 - 3 (walking) vs. 4 - 6, and 0 - 4 vs. 5 - 6 (bedridden or death), and shift analysis)
Any intracranial hemorrhage (ICH) at visit 2 72 hours Any ICH (except microhemorrhages) on follow-up magnetic resonance imaging; in case of missing follow-up brain imaging due to premature death, ICH will be replaced by "ICH or death without repeat scan")
Major bleeding until visit 2 72 hours Major bleeding, defined as clinically overt bleeding associated with at least one of the following features: decrease in hemoglobin levels of ≥ 2 g/dL over 24 hours, bleeding requiring transfusion of ≥ 2 units of packed red cells, bleeding at a critical site (i.e., intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal), or bleeding resulting in the death of the patient
Retinal neovascularization requiring therapy at visit 3 and 4 90 days Retinal neovascularization requiring therapy
Trial Locations
- Locations (1)
University Hospital Tuebingen
🇩🇪Tuebingen, Germany