Comparison of Thrombectomy and Standard Care for Ischemic Stroke in Patients Ineligibility for Tissue Plasminogen Activator Treatment (THRILL)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Thrombectomy in Patients Ineligible for iv tPA|
- mRS Shift [ Time Frame: 90 (+/-14) days after treatment ] [ Designated as safety issue: No ]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.
- Neurological outcome [ Time Frame: 90 (+/- 14) days after treatment ] [ Designated as safety issue: No ]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 [ Time Frame: 90 (+/-14) days after treatment ] [ Designated as safety issue: No ]Functional health status and quality of life 90 (±14) days after stroke (EQ-5D)
- Infarct volume [ Time Frame: 30 (-/+ 6) hours after treatment ] [ Designated as safety issue: No ]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 [ Time Frame: 30 (-/+ 6) hours after treatment ] [ Designated as safety issue: No ]For the endovascular treatment group successful recanalization will be defined as Thrombolysis in Cerebral Infarction scale (TICI) 2b or 3.
- Safety endpoints [ Time Frame: within 90 (+/- 14) days after treatment ] [ Designated as safety issue: Yes ]
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
|Study Start Date:||March 2014|
|Estimated Study Completion Date:||March 2018|
|Estimated Primary Completion Date:||February 2018 (Final data collection date for primary outcome measure)|
Active Comparator: Best medical care
Best clinical care in dedicated stroke unit
Other: Best 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.).
Active Comparator: Thrombectomy
All subjects randomly assigned to the thrombectomy arm, except those with rapidly improving neurologic symptoms or no angiographic evidence of occlusion, will be treated with the endorsed study devices (stent retriever).
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.
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 subject‟s 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").
Please refer to this study by its ClinicalTrials.gov identifier: NCT02135926
|Institut für Radiologie Oö. Gesundheits- und Spitals-AG Landes-Nervenklinik Wagner-Jauregg|
|Linz, Austria, 4020|
|Klinik für Diagnostische und Interventionelle Neuroradiologie Universitätsklinikum Aachen|
|Aachen, Germany, 52074|
|Klinische und interventionelle Neuroradiologie Vivantes Klinikum Neukölln|
|Berlin, Germany, 12351|
|University Clinic Bochum|
|Institut für Diagnostische und Interventionelle Radiologie, Neuroradiologie und Nuklearmedizin Universitätsklinikum Knappschaftskrankenhaus Bochum|
|Bochum, Germany, 44892|
|Kinik für Radiologie und Neuroradiologie|
|Dortmund, Germany, 44137|
|Abteilung für Neuroradiologie Universitätsklinikum Erlangen|
|Erlangen, Germany, 91054|
|Klinik für Radiologie und Neuroradiologie Alfried Krupp Krankenhaus|
|Essen, Germany, 45131|
|Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie Universitätsklinikum Essen|
|Essen, Germany, 45147|
|Klinik für Neuroradiologie Universitätsklinikum Freiburg|
|Freiburg, Germany, 79106|
|Institut für Diagnostische & Interventionelle Neuroradiologie Universitätsmedizin Göttingen|
|Goettingen, Germany, 37075|
|Klinik und Poliklinik für Neuroradiologische Diagnostik und Intervention|
|Hamburg, Germany, 20246|
|Asklepios Klinik Altona|
|Hamburg, Germany, 22763|
|Universität Heidelberg, Neuroradiologie|
|Heidelberg, Germany, 69120|
|Diagnostik , Neuroradiologie, Universitätsklinikum Köln|
|Köln, Germany, 50937|
|Abteilung für Neuroradiologie Klinikum der Universität München Campus|
|München, Germany, 81377|
|Abteilung für Diagnostische & Interventionelle Neuroradiogie Klinikum rechts der Isar der TU München|
|München, Germany, 81675|
|Klinik für Radiologie, Neuroradiologie und Nuklearmedizin Behandlungszentrum Knappschaftskrankenhaus Recklinghausen|
|Recklinghausen, Germany, 45657|
|Abteilung für Neuroradiologie Universitätsklinikum Würzburg|
|Würzburg, Germany, 97080|
|Principal Investigator:||Martin Bendszus, MD||University Hospital Heidelberg|