Clinical trial NCT05273216: Reperfusion Injury After Endovascular Stroke Treatment
Official title: Hemodynamic Changes and Reperfusion Injury After Endovascular Stroke Treatment: Prospective Multicenter DYNASTROKE STUDY
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ischemic Stroke
Keywords: Endovascular Stroke Treatment
Mechanical Thrombectomy
Reperfusion Injury
Intracranial Hemorrhage
Transcranial Duplex Sonography
Perfusion MRI
Cerebral Hyperperfusion
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: Medical University Innsbruck
name: Paracelsus Medical University
First posted: 2022-03-10
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with acute ischemic stroke due to large vessel occlusion of the anterior cerebral circulation (internal carotid artery, middle cerebral artery) receiving mechanical thrombectomy.

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.

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

Primary outcomes:
measure: Rate of intracranial hemorrhage
timeFrame: Day one after mechanical thrombectomy
measure: Rate of (vasogenic) brain edema
timeFrame: Day one after mechanical thrombectomy
Secondary outcomes:
measure: Cerebral blood flow changes on TCD
timeFrame: Immediately, 24-48 hours and 7 days post-thrombectomy, and after 3 months poststroke
measure: Change of symptomatic intracranial hemorrhage
timeFrame: Immediately, 24-48 hours and 7 days post-thrombectomy.
measure: Inhospital mortality
timeFrame: Median inhospital stay of 7 days
measure: Change of functional neurological outcome
timeFrame: Hospital discharge (median of 7 days) and after 3 months poststroke
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical Univerity of Graz, Department of Neurology
state: Styria
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck, Department of Neurology
state: Tyrol
city: Salzburg
country: Austria
facility: Paracelsus Medical University, Department of Neurology
Study officials:
References: