Reperfusion Injury After Endovascular Stroke Treatment
- Conditions
- Ischemic Stroke
- Interventions
- Diagnostic Test: Transcranial Duplex SonographyDiagnostic Test: Brain MRIDiagnostic Test: Blood biomarkers
- Registration Number
- NCT05273216
- Lead Sponsor
- Medical University of Graz
- Brief Summary
Endovascular stroke treatment with mechanical thrombectomy (MT) has become the standard therapy for intracranial large vessel occlusion (LVO). The most serious MT-related complication is secondary intracranial hemorrhage (ICH) occurring in 20-25%. Post- recanalization hyperperfusion might be an important risk factor/mechanism of MT-related ICH. In pilot studies, bedside transcranial Duplex sonography (TCD) was identified as a promising screening tool for cerebral hyperperfusion predicting ICH - the hallmark feature of reperfusion injury.
There is an unmet need to identify risk factors for ICH after MT as it relates to poor prognosis, no proven treatment is available, and it delays/prohibits usage of anticoagulants/-thrombotics necessary for preventing recurrent stroke.
Main objectives:
To explore the range and clinical impact of hemodynamic changes after MT as detected on bedside TCD.
To assess whether patients with increased blood flow velocity in the recanalized middle cerebral artery (MCA) are at a higher risk to develop ICH / vasogenic brain edema (reperfusion injury) after MT.
To investigate if the underlying mechanism is cerebral hyperperfusion (confirmed by perfusion MRI).
To additionally study the role of blood biomarkers of blood-brain-barrier / endothelial dysfunction and neuroaxonal damage on reperfusion injury and short-term prognosis.
Approach / methods:
Prospective, longitudinal Austrian multicentre study conducted at three high-volume stroke centers (Graz, Innsbruck, Salzburg). The investigators will recruit consecutive stroke patients with anterior circulation L VO treated by MT. Immediately after MT, experienced sonographers will perform bedside TCD to determine MCA blood flow status, which will be repeated after 24-48h and on day 7. On day one after MT, brain MRI with perfusion serves to assess infarct size, secondary ICH, (vasogenic) brain edema and perfusion status. MRI will be centrally analyzed in the neuroimaging lab of Graz, blinded to clinical, laboratory and sonographic information. Blood samples for the analysis of biomarkers of endothelial (blood-brain barrier) dysfunction and neuroaxonal damage (neurofilament light) will be taken on day one and at three months post-MT. Neurological outcome will be rated according to the modified Rankin Scale at three months post-stroke.
- Detailed Description
Endovascular stroke treatment with mechanical thrombectomy (MT) has become the standard therapy for intracranial large vessel occlusion (LVO). The most serious MT-related complication is secondary intracranial hemorrhage (ICH) occurring in 20-25%. Post- recanalization hyperperfusion might be an important risk factor/mechanism of MT-related ICH. In pilot studies, bedside transcranial Duplex sonography (TCD) was identified as a promising screening tool for cerebral hyperperfusion predicting ICH - the hallmark feature of reperfusion injury.
There is an unmet need to identify risk factors for ICH after MT as it relates to poor prognosis, no proven treatment is available, and it delays/prohibits usage of anticoagulants/-thrombotics necessary for preventing recurrent stroke.
Main objectives:
To explore the range and clinical impact of hemodynamic changes after MT as detected on bedside TCD.
To assess whether patients with increased blood flow velocity in the recanalized middle cerebral artery (MCA) are at a higher risk to develop ICH / vasogenic brain edema (reperfusion injury) after MT.
To investigate if the underlying mechanism is cerebral hyperperfusion (confirmed by perfusion MRI).
To additionally study the role of blood biomarkers of blood-brain-barrier / endothelial dysfunction and neuroaxonal damage on reperfusion injury and short-term prognosis.
Approach / methods:
Prospective, longitudinal Austrian multicentre study conducted at three high-volume stroke centers (Graz, Innsbruck, Salzburg). The investigators will recruit consecutive stroke patients with anterior circulation L VO treated by MT. Immediately after MT, experienced sonographers will perform bedside TCD to determine MCA blood flow status, which will be repeated after 24-48h and on day 7. On day one after MT, brain MRI with perfusion serves to assess infarct size, secondary ICH, (vasogenic) brain edema and perfusion status. MRI will be centrally analyzed in the neuroimaging lab of Graz, blinded to clinical, laboratory and sonographic information. Blood samples for the analysis of biomarkers of endothelial (blood-brain barrier) dysfunction and neuroaxonal damage (neurofilament light) will be taken on day one and at three months post-MT. Neurological outcome will be rated according to the modified Rankin Scale at three months post-stroke.
Level of originality:
Human studies on reperfusion injury after MT are lacking. If the investigator's hypothesis would hold true and the investigators could show that cerebral hemodynamic changes after MT would increase the risk for post-interventional intracranial bleeding complications and poor outcome, the investigators would provide an easy-available, repeatable bedside screening and monitoring tool (TCD), which has the potential to guide individualized patient treatment in the early postinterventional period after MT.
The study was registered on Clinicaltrials.gov after start of recruitment.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 600
- stroke due to large vessel occlusion of the anterior cerebral circulation (internal carotid artery, middle cerebral artery) receiving mechanical thrombectomy.
- basilar artery occlusion
- age below 18 years
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Observational Study (no different study arms) Blood biomarkers Prospective, longitudinal, multicenter, observational study to investigate hemodynamic changes (by TCD and perfusion MRI) and blood biomarkers as predictors of reperfusion injury / intracranial hemorrhage after stroke thrombectomy of the anterior cerebral circulation Observational Study (no different study arms) Transcranial Duplex Sonography Prospective, longitudinal, multicenter, observational study to investigate hemodynamic changes (by TCD and perfusion MRI) and blood biomarkers as predictors of reperfusion injury / intracranial hemorrhage after stroke thrombectomy of the anterior cerebral circulation Observational Study (no different study arms) Brain MRI Prospective, longitudinal, multicenter, observational study to investigate hemodynamic changes (by TCD and perfusion MRI) and blood biomarkers as predictors of reperfusion injury / intracranial hemorrhage after stroke thrombectomy of the anterior cerebral circulation
- Primary Outcome Measures
Name Time Method Rate of intracranial hemorrhage Day one after mechanical thrombectomy Rate of intracranial hemorrhage (indicator of reperfusion injury) on neuroimaging at day one after mechanical thrombectomy.
Rate of (vasogenic) brain edema Day one after mechanical thrombectomy Rate of (vasogenic) brain edema (indicator of reperfusion injury) on neuroimaging at day one after mechanical thrombectomy.
- Secondary Outcome Measures
Name Time Method Inhospital mortality Median inhospital stay of 7 days Early inhospital mortality
Change of symptomatic intracranial hemorrhage Immediately, 24-48 hours and 7 days post-thrombectomy. Rate of symptomatic intracranial hemorrhage post-thrombectomy.
Change of functional neurological outcome Hospital discharge (median of 7 days) and after 3 months poststroke Functional neurological outcome (according to the modified Rankin Scale with score of 0-6; higher scores indicating more severe disability) including mortality at three months post-stroke.
Cerebral blood flow changes on TCD Immediately, 24-48 hours and 7 days post-thrombectomy, and after 3 months poststroke The range of cerebral blood flow changes on TCD and its correlation with perfusion MRI.
Trial Locations
- Locations (3)
Medical Univerity of Graz, Department of Neurology
🇦🇹Graz, Styria, Austria
Paracelsus Medical University, Department of Neurology
🇦🇹Salzburg, Austria
Medical University of Innsbruck, Department of Neurology
🇦🇹Innsbruck, Tyrol, Austria