Clinical trial NCT04965038: Early Reperfusion Therapy With Intravenous Thrombolysis for Recovery of VISION in Acute Central Retinal Artery Occlusion
Official title: Early Reperfusion Therapy With Intravenous Thrombolysis for Recovery of VISION in Acute Central Retinal Artery Occlusion
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Central Retinal Artery Occlusion
Keywords: Central Retinal Artery Occlusion
Thrombolysis
Alteplase
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2021-07-16
Enrollment: 422
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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

Primary outcomes:
measure: Functional recovery at visit 3
timeFrame: 30 days
Secondary outcomes:
measure: best corrected visual acuity (BCVA) at visits 2, 3, and 4
timeFrame: 90 days
measure: Shift in visual outcome categories at visits 2, 3, and 4
timeFrame: 90 days
measure: Dichotomized analysis of visual outcome at visits 2, 3, and 4
timeFrame: 90 days
measure: Visual field at visits 3 and 4
timeFrame: 90 days
measure: Central retinal artery recanalization at visits 2, 3, and 4
timeFrame: 90 days
measure: Retinal arterial perfusion at visits 3 and 4
timeFrame: 90 days
measure: National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) at visits 3 and 4
timeFrame: 90 days
measure: National Institutes of Health Stroke Scale (NIHSS) score at visit 2
timeFrame: 72 hours
measure: Modified Rankin Scale (mRS) score at visits 3 and 4
timeFrame: 90 days
measure: Fresh ischemic lesions on cranial magnetic resonance imaging (MRI) at visit 2
timeFrame: 72 hours
measure: Death at visits 3 and 4
timeFrame: 90 days
measure: Any intracranial hemorrhage (ICH) at visit 2
timeFrame: 72 hours
measure: Symptomatic intracranial hemorrhage (ICH) until visit 2
timeFrame: 72 hours
measure: Intraocular hemorrhage in the affected eye at visit 2
timeFrame: 72 hours
measure: Major bleeding until visit 2
timeFrame: 72 hours
measure: Retinal neovascularization requiring therapy at visit 3 and 4
timeFrame: 90 days
measure: (Serious) adverse events ((S)AE)
timeFrame: 90 days
Other outcomes:
measure: Exploratory Outcomes of the REVISION Interventional Study
timeFrame: 90 days
measure: Exploratory Outcomes of the REVISION Observational Study
timeFrame: 1 day
measure: Exploratory Outcomes of the Retrobulbar Spot Sign Substudy
timeFrame: 30 days
Locations:
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen
Study officials:
References: