Ischemic Stroke
Conditions
Keywords
Cerebral Stroke, Stroke, Acute, Brain Infarction
Brief summary
the purpose of this study is to to compare the safety and effectiveness of stent-retrievers as a device class group with best medical care alone in the treatment of acute ischemic stroke (AIS) in patients who are not eligible for IV-tPA up to 8 hours of symptom onset.
Detailed description
This is a prospective, binational (Germany and Austria), two-arm, randomized, controlled, open label, blinded endpoint post-market study to compare the safety and effectiveness of stent retrievers for thrombectomy compared to best medical treatment alone in acute ischemic stroke (AIS) patients not eligible for IV-tPA treatment. Patients who meet the inclusion criteria will be randomized to one of the following two treatment arms: * best medical care alone or * best medical care plus endovascular thrombectomy with stent retriever (referred to as thrombectomy). Endpoints in this prospective open label study will be assessed blinded to the treatment assignment of the patient (PROBE design). This study will be conducted in up to 20 centers in Germany and Austria. This is an adaptive design study, in which there are prospectively stated interim analyses with specified stopping rules, which allow for the possibility of the study to terminate early based on either a determination of study success or of the futility to continue further enrollment. Up to six hundred (600) subjects, 300 per treatment group, will be enrolled and randomized in the study for the Intent to Treat (ITT) analysis set. The randomization will be stratified by time from symptom onset and stroke severity (NIHSS). The expected duration of each subjects enrollment is approximately 90 days. Subjects will be followed with assessments at 30 (+/-6) hours, hospital discharge, and 90 (+/-14) days post stroke. A blinded core laboratory will assess baseline imaging to confirm vessel occlusion and determine ASPECT score, 30 (+/- 6) hours post treatment imaging to assess presence of ICH, and to measure core infarct volume. The primary effectiveness endpoint for a subject is the blinded evaluation of the ordinal mRS outcome at 90 days post-stroke. The primary effectiveness endpoint analysis is a chi-square test of the difference in linear trends in mRS outcomes at 90 days post-stroke between treatment groups (mRS shift analysis).
Interventions
DEVICEThrombectomy
Stent retriever are intended to restore blood flow in patients with acute ischemic stroke secondary to intracranial occlusive vessel disease by providing temporary bypass across the occlusion and/or by the non-surgical removal of emboli and thrombi. They may be used with aspiration and with the injection or infusion of contrast media and/or other fluids. For subjects enrolled in this protocol who are randomly assigned to undergo the thrombectomy procedure, the device will be used according to the Instructions-for-Use (IFU) that is packaged with the device.
OTHERBest medical care
Best medical treatment will be performed as detailed in established Standard Operating Procedures, following regional guidelines (American Heart Association (AHA), European Stroke Organisation (ESO), Deutsche Schlaganfall-Gesellschaft (DSG), local country, etc.).
Sponsors
University Hospital, Aachen
University Hospital Augsburg
Vivantes Krankenhaus Berlin Neukölln
Ruhr University of Bochum
Klinikum Dortmund Wirbelsäulenchirurgie
University of Erlangen-Nürnberg Medical School
Alfried Krupp Krankenhaus
University Hospital, Essen
University Hospital Freiburg
University Medical Center Goettingen
Universitätsklinikum Hamburg-Eppendorf
Universitätsklinik für Neurologie, Innsbruck
Universitätsklinikum Köln
The Wagner-Jauregg Provincial Neuropsychiatric Clinic
LMU Klinikum
Klinikum rechst der Isar Technische Universitaet Muenchen
KLINIKUM VEST Recklinghausen
Wuerzburg University Hospital
Asklepios Kliniken Hamburg GmbH
University Hospital Heidelberg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patient is ineligible for treatment with IV tPA according to licensing criteria (e.g. anticoagulation, previous surgery, or beyond 4.5 hours after symptom onset). * Randomization within 7 hours after stroke onset. * Endovascular treatment is expected to be finished within 8 hours after symptom onset by judgment of the interventional Neuroradiologist in charge. * Patient must demonstrate clinical signs and symptoms attributable to target area of occlusion consistent with the diagnosis of ischemic stroke, including impairment of the following: language, motor function, sensation, cognition, gaze, and/or vision for at least 30 minutes without relevant improvement. * Female and male patient between 18-80 years of age * NIHSS Score of \>7 and \<25 * Patient signed informed consent (IC) form by patient, legal representative, or by an independent physician who is familiar with this types of illness if the other options are not possible. * A new focal occlusion confirmed by imaging (MRA/CTA) to be accessible to the thrombectomy device, and located in the M1 of the middle cerebral artery (MCA) and/or the intracranial segment of the distal internal carotid artery (ICA). * Prior to new focal neurological deficit, mRS score was ≤1.
Exclusion criteria
* Patient is eligible for and receives IV tPA according to licensing criteria * Patient with an international normalized ratio (INR) of \>3 * Patient is an active participant in another drug or device treatment trial for any disease state, or patient is expected to start participation in another drug or device treatment trial while enrolled in this protocol, unless approved by Sponsor. * Patient has pre-existing neurological or psychiatric disease that could impede the study results or would confound the neurological or functional evaluations. * Patient has carotid dissection, high grade stenosis ≥ 70% proximal to occlusion that requires stenting, or excessive tortuosity to gain access to occlusion, as determined by MRA/ CTA of neck and head. * Patient has vascular disease preventing endovascular treatment (e.g. aortic dissection or aneurysm, no arterial transfemoral access) * Patient has history of contraindication for contrast medium. * Patient is known to have infective endocarditis * CT scan or MRI with evidence of: Mass effect or intracranial tumor, or hypodensity on unenhanced CT and cerebral blood volume (CBV) drop on CBV maps on Computed Tomography Perfusion (CTP), or, alternatively as per institutional standard, restricted diffusion on Diffusion weighted imaging (DWI) with an Alberta Stroke Program Early CT score (ASPECTs) of 6 or less * Female of childbearing potential who is known to be pregnant and/or lactating or who has a positive pregnancy test on admission. * Patients anticipated life expectancy is less than 6 Months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| mRS Shift | 90 (+/-14) days after treatment | The primary endpoint of the trial is the modified Rankin Scale (mRS) outcome at 90 days poststroke. The primary effectiveness endpoint analysis is a chi-square test of the difference in linear trends in ordinal mRS outcomes at 90 days postprocedure between treatment groups (mRS shift analysis). The null and alternative hypotheses are β ≥ 0 and β \< 0, respectively, where β is the treatment arm parameter in a proportional-odds logistic model with mRS category as response variable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurological outcome | 90 (+/- 14) days after treatment | Good neurological outcome with 90-day modified rankin Scale (mRS) ≤2 Good neurological outcome with 90-day NIHSS (National Institutes of Health Stroke Scale) improvement ≥10 from baseline Excellent neurological outcomes with 90-day mRS≤1 |
| Health Status | 90 (+/-14) days after treatment | Functional health status and quality of life 90 (±14) days after stroke (EQ-5D) |
| Infarct volume | 30 (-/+ 6) hours after treatment | Infarct volume at 30 (-/+ 6) hours based on Computer Tomography or Magnetic Resonance Imaging compare to predicted infarct volume at time of patients hospital admission. |
| Successful Recanalization | 30 (-/+ 6) hours after treatment | For the endovascular treatment group successful recanalization will be defined as Thrombolysis in Cerebral Infarction scale (TICI) 2b or 3. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety endpoints | within 90 (+/- 14) days after treatment | Number of patients with any of the following: * Death or dependency (mRS 5-6) * Symptomatic intracranial haemorrhage (sICH) at 30 (-/+ 6) hours (CT or MRI) as defined in Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), European Cooperative Acute Stroke Study (ECASS) II, National Institute of Neurological Disorders and Stroke (NINDS); * Parenchymal hemorrhage type 2 (PH-2) * Neurological deterioration within 7 days defined as an increase in NIHSS score by 4 or more points from baseline * Adverse Events (AEs) * Serious AEs (SAEs), * Adverse Device Effects (ADEs), and * Serious Adverse Device Effects (SADEs) including Unanticipated Adverse Device Effects (UADEs attributed to the stent retriever, reported in the interventional treatment arm * Mortality rates at discharge and 90 days post-stroke * Overall (all-cause mortality) death and stroke-related death * Space-occupying infarction (malignant brain edema) * New ischemic stroke |
Countries
Austria, Germany
Outcome results
None listed