Reperfusion Injury After Endovascular Stroke Treatment
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Transcranial Duplex Sonography, Brain MRI, Blood biomarkers.
- Who it may be relevant to
- Registry conditions: Ischemic Stroke. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Austria
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Hemodynamic Changes and Reperfusion Injury After Endovascular Stroke Treatment: Prospective Multicenter DYNASTROKE STUDY
Overview
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.
Interventions
- Diagnostic test Transcranial Duplex Sonography
Immediately after mechanical thrombectomy, patients will be investigated with bedside neurosonography (including TCD) at the stroke unit or neurointensive care unit. Apart from routine assessment of brain-supplying vessels, experienced sonographers will especially focus on intracranial blood flow velocities and determine the MCA mean blood flow velocity index (recanalized divided by contralateral artery). To assess potential dynamic blood flow changes, these investigations will be repeated at 24 - Diagnostic test Brain MRI
The investigators will use magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) routinely performed on day 1 after thrombectomy to assess (1) the size and location of acute ischemic damage including (vasogenic) cerebral edema formation, (2) hemorrhagic transformation, (3) concomitant chronic ischemic and hemorrhagic brain changes, and (4) patency of intracranial vessels. Contrast-enhanced or arterial spin labeling perfusion MRI will be used to (5) measure cerebral perfusion - Diagnostic test Blood biomarkers
Apart from the assessment of outcome-relevant routine blood parameters of inflammation, coagulation, glucose metabolism, renal and liver function, the investigators will also investigate novel biomarkers of interest that could be indicative of endothelial damage / blood brain barrier disruption. Candidate markers for this purpose are interleukins (i.e., interleukin-6) and matrix metalloproteinases (i.e., MMP-9). Furthermore, the investigators will also measure neurofilament light chain protein a
Primary outcome measures
- Rate of intracranial hemorrhage [Time frame: Day one after mechanical thrombectomy]
- Rate of (vasogenic) brain edema [Time frame: Day one after mechanical thrombectomy]
Secondary outcome measures (4)
- Cerebral blood flow changes on TCD [Time frame: Immediately, 24-48 hours and 7 days post-thrombectomy, and after 3 months poststroke]
- Change of symptomatic intracranial hemorrhage [Time frame: Immediately, 24-48 hours and 7 days post-thrombectomy.]
- Inhospital mortality [Time frame: Median inhospital stay of 7 days]
- Change of functional neurological outcome [Time frame: Hospital discharge (median of 7 days) and after 3 months poststroke]
Eligibility criteria
Inclusion criteria
- stroke due to large vessel occlusion of the anterior cerebral circulation (internal carotid artery, middle cerebral artery) receiving mechanical thrombectomy.
Exclusion criteria
- basilar artery occlusion
- age below 18 years
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Austria · 3 centers
- Medical Univerity of Graz, Department of Neurology — Graz
- Medical University of Innsbruck, Department of Neurology — Innsbruck
- Paracelsus Medical University, Department of Neurology — Salzburg
Identifiers
NCT: NCT05273216 · EK 30-254 ex 17/18