Thrombectomy in Patients Ineligible for iv tPA

Ischemic Stroke Clinical Trial

— THRILL  

Official title:

Comparison of Thrombectomy and Standard Care for Ischemic Stroke in Patients Ineligibility for Tissue Plasminogen Activator Treatment

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02135926
• Other study ID #: UH-Heidelberg-THRILL
• Secondary ID: DRKS00005792
• Status: Terminated
• Phase: N/A
• Start date: March 2014
• Est. completion date: February 1, 2017

Study information

• Verified date: June 2018
• Source: University Hospital Heidelberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 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").

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: February 1, 2017
• Est. primary completion date: February 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

• Patient?s anticipated life expectancy is less than 6 Months.

Related Conditions & MeSH terms

• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Device:
• Thrombectomy
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.

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.).

Locations

Country	Name	City	State
Austria	Institut für Radiologie Oö. Gesundheits- und Spitals-AG Landes-Nervenklinik Wagner-Jauregg	Linz
Germany	Klinik für Diagnostische und Interventionelle Neuroradiologie Universitätsklinikum Aachen	Aachen
Germany	Klinische und interventionelle Neuroradiologie Vivantes Klinikum Neukölln	Berlin
Germany	Institut für Diagnostische und Interventionelle Radiologie, Neuroradiologie und Nuklearmedizin Universitätsklinikum Knappschaftskrankenhaus Bochum	Bochum
Germany	University Clinic Bochum	Bochum
Germany	Kinik für Radiologie und Neuroradiologie	Dortmund
Germany	Abteilung für Neuroradiologie Universitätsklinikum Erlangen	Erlangen
Germany	Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie Universitätsklinikum Essen	Essen
Germany	Klinik für Radiologie und Neuroradiologie Alfried Krupp Krankenhaus	Essen
Germany	Klinik für Neuroradiologie Universitätsklinikum Freiburg	Freiburg
Germany	Institut für Diagnostische & Interventionelle Neuroradiologie Universitätsmedizin Göttingen	Goettingen
Germany	Asklepios Klinik Altona	Hamburg
Germany	Klinik und Poliklinik für Neuroradiologische Diagnostik und Intervention	Hamburg
Germany	Universität Heidelberg, Neuroradiologie	Heidelberg
Germany	Diagnostik , Neuroradiologie, Universitätsklinikum Köln	Köln
Germany	Abteilung für Diagnostische & Interventionelle Neuroradiogie Klinikum rechts der Isar der TU München	München
Germany	Abteilung für Neuroradiologie Klinikum der Universität München Campus	München
Germany	Klinik für Radiologie, Neuroradiologie und Nuklearmedizin Behandlungszentrum Knappschaftskrankenhaus Recklinghausen	Recklinghausen
Germany	Abteilung für Neuroradiologie Universitätsklinikum Würzburg	Würzburg

Sponsors (20)

Lead Sponsor

Collaborator

University Hospital Heidelberg

Alfried Krupp Krankenhaus Essen, Asklepios Kliniken Hamburg GmbH, Klinikum Augsburg, Klinikum der Universitaet Muenchen, Klinikum Dortmund Wirbelsäulenchirurgie, Klinikum rechst der Isar Technische Universitaet Muenchen, KLINIKUM VEST Recklinghausen, Ruhr University of Bochum, The Wagner-Jauregg Provincial Neuropsychiatric Clinic, Universitätsklinik für Neurologie, Innsbruck, Universitätsklinikum Hamburg-Eppendorf, Universitätsklinikum Köln, University Hospital Freiburg, University Hospital, Aachen, University Hospital, Essen, University Medical Center Goettingen, University of Erlangen-Nürnberg Medical School, Vivantes Krankenhaus Berlin Neukölln, Wuerzburg University Hospital

Countries where clinical trial is conducted

Austria,  Germany, 

References & Publications (5)

Albers GW, Goldstein LB, Hess DC, Wechsler LR, Furie KL, Gorelick PB, Hurn P, Liebeskind DS, Nogueira RG, Saver JL; STAIR VII Consortium. Stroke Treatment Academic Industry Roundtable (STAIR) recommendations for maximizing the use of intravenous thrombolytics and expanding treatment options with intra-arterial and neuroprotective therapies. Stroke. 2011 Sep;42(9):2645-50. doi: 10.1161/STROKEAHA.111.618850. Epub 2011 Aug 18. — View Citation

Kelly ME, Furlan AJ, Fiorella D. Recanalization of an acute middle cerebral artery occlusion using a self-expanding, reconstrainable, intracranial microstent as a temporary endovascular bypass. Stroke. 2008 Jun;39(6):1770-3. doi: 10.1161/STROKEAHA.107.506212. Epub 2008 Apr 3. — View Citation

Nogueira RG, Lutsep HL, Gupta R, Jovin TG, Albers GW, Walker GA, Liebeskind DS, Smith WS; TREVO 2 Trialists. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet. 2012 Oct 6;380(9849):1231-40. doi: 10.1016/S0140-6736(12)61299-9. Epub 2012 Aug 26. Erratum in: Lancet. 2012 Oct 6;380(9849):1230. — View Citation

Penumbra Pivotal Stroke Trial Investigators. The penumbra pivotal stroke trial: safety and effectiveness of a new generation of mechanical devices for clot removal in intracranial large vessel occlusive disease. Stroke. 2009 Aug;40(8):2761-8. doi: 10.1161/STROKEAHA.108.544957. Epub 2009 Jul 9. — View Citation

Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG, Clark W, Budzik R, Zaidat OO; SWIFT Trialists. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet. 2012 Oct 6;380(9849):1241-9. doi: 10.1016/S0140-6736(12)61384-1. Epub 2012 Aug 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety endpoints	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	within 90 (+/- 14) days after treatment
Primary	mRS Shift	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 ß = 0 and ß < 0, respectively, where ß is the treatment arm parameter in a proportional-odds logistic model with mRS category as response variable.	90 (+/-14) days after treatment
Secondary	Neurological outcome	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	90 (+/- 14) days after treatment
Secondary	Health Status	Functional health status and quality of life 90 (±14) days after stroke (EQ-5D)	90 (+/-14) days after treatment
Secondary	Infarct volume	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.	30 (-/+ 6) hours after treatment
Secondary	Successful Recanalization	For the endovascular treatment group successful recanalization will be defined as Thrombolysis in Cerebral Infarction scale (TICI) 2b or 3.	30 (-/+ 6) hours after treatment

External Links

•   THRILL 'Thrombectomy in patients ineligible for iv tPA' Study Website