Thrombectomy in Patients Ineligible for iv tPA

NCT ID: NCT02135926

Last Updated: 2018-06-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

4 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-31

Study Completion Date

2017-02-01

Brief Summary

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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

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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").

Conditions

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Ischemic Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Best medical care

Best clinical care in dedicated stroke unit

Group Type ACTIVE_COMPARATOR

Best medical care

Intervention Type OTHER

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.).

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).

Group Type ACTIVE_COMPARATOR

Thrombectomy

Intervention Type DEVICE

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.

Interventions

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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.

Intervention Type DEVICE

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.).

Intervention Type OTHER

Other Intervention Names

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Stent Retrievers Solitaire (Covidien) Trevo (Stryker) clinical care conservative treatment

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Aachen

OTHER

Sponsor Role collaborator

University Hospital Augsburg

OTHER

Sponsor Role collaborator

Vivantes Krankenhaus Berlin Neukölln

UNKNOWN

Sponsor Role collaborator

Ruhr University of Bochum

OTHER

Sponsor Role collaborator

Klinikum Dortmund Wirbelsäulenchirurgie

OTHER

Sponsor Role collaborator

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role collaborator

Alfried Krupp Krankenhaus

OTHER

Sponsor Role collaborator

University Hospital, Essen

OTHER

Sponsor Role collaborator

University Hospital Freiburg

OTHER

Sponsor Role collaborator

University Medical Center Goettingen

OTHER

Sponsor Role collaborator

Universitätsklinikum Hamburg-Eppendorf

OTHER

Sponsor Role collaborator

Universitätsklinik für Neurologie, Innsbruck

OTHER

Sponsor Role collaborator

Universitätsklinikum Köln

OTHER

Sponsor Role collaborator

The Wagner-Jauregg Provincial Neuropsychiatric Clinic

INDIV

Sponsor Role collaborator

LMU Klinikum

OTHER

Sponsor Role collaborator

Klinikum rechst der Isar Technische Universitaet Muenchen

UNKNOWN

Sponsor Role collaborator

KLINIKUM VEST Recklinghausen

UNKNOWN

Sponsor Role collaborator

Wuerzburg University Hospital

OTHER

Sponsor Role collaborator

Asklepios Kliniken Hamburg GmbH

OTHER

Sponsor Role collaborator

University Hospital Heidelberg

OTHER

Sponsor Role lead

Responsible Party

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Susanne Bonekamp

Prof. Dr. Martin Bendszus

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Martin Bendszus, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Heidelberg

Locations

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Institut für Radiologie Oö. Gesundheits- und Spitals-AG Landes-Nervenklinik Wagner-Jauregg

Linz, , Austria

Site Status

Klinik für Diagnostische und Interventionelle Neuroradiologie Universitätsklinikum Aachen

Aachen, , Germany

Site Status

Klinische und interventionelle Neuroradiologie Vivantes Klinikum Neukölln

Berlin, , Germany

Site Status

Institut für Diagnostische und Interventionelle Radiologie, Neuroradiologie und Nuklearmedizin Universitätsklinikum Knappschaftskrankenhaus Bochum

Bochum, , Germany

Site Status

University Clinic Bochum

Bochum, , Germany

Site Status

Diagnostik , Neuroradiologie, Universitätsklinikum Köln

Cologne, , Germany

Site Status

Kinik für Radiologie und Neuroradiologie

Dortmund, , Germany

Site Status

Abteilung für Neuroradiologie Universitätsklinikum Erlangen

Erlangen, , Germany

Site Status

Klinik für Radiologie und Neuroradiologie Alfried Krupp Krankenhaus

Essen, , Germany

Site Status

Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie Universitätsklinikum Essen

Essen, , Germany

Site Status

Klinik für Neuroradiologie Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Site Status

Institut für Diagnostische & Interventionelle Neuroradiologie Universitätsmedizin Göttingen

Göttingen, , Germany

Site Status

Klinik und Poliklinik für Neuroradiologische Diagnostik und Intervention

Hamburg, , Germany

Site Status

Asklepios Klinik Altona

Hamburg, , Germany

Site Status

Universität Heidelberg, Neuroradiologie

Heidelberg, , Germany

Site Status

Abteilung für Neuroradiologie Klinikum der Universität München Campus

München, , Germany

Site Status

Abteilung für Diagnostische & Interventionelle Neuroradiogie Klinikum rechts der Isar der TU München

München, , Germany

Site Status

Klinik für Radiologie, Neuroradiologie und Nuklearmedizin Behandlungszentrum Knappschaftskrankenhaus Recklinghausen

Recklinghausen, , Germany

Site Status

Abteilung für Neuroradiologie Universitätsklinikum Würzburg

Würzburg, , Germany

Site Status

Countries

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Austria Germany

References

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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.

Reference Type BACKGROUND
PMID: 18388338 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22932714 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19590057 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22932715 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21852620 (View on PubMed)

Kastner B, Behre S, Lutz N, Burger F, Luntz S, Hinderhofer K, Bendszus M, Hoffmann GF, Ries M. Clinical Research in Vulnerable Populations: Variability and Focus of Institutional Review Boards' Responses. PLoS One. 2015 Aug 14;10(8):e0135997. doi: 10.1371/journal.pone.0135997. eCollection 2015.

Reference Type DERIVED
PMID: 26275228 (View on PubMed)

Bendszus M, Thomalla G, Knauth M, Hacke W, Bonekamp S, Fiehler J. Thrombectomy in patients ineligible for iv tPA (THRILL). Int J Stroke. 2015 Aug;10(6):950-5. doi: 10.1111/ijs.12527. Epub 2015 Jun 4.

Reference Type DERIVED
PMID: 26044962 (View on PubMed)

Other Identifiers

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DRKS00005792

Identifier Type: REGISTRY

Identifier Source: secondary_id

UH-Heidelberg-THRILL

Identifier Type: -

Identifier Source: org_study_id

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