Clinical trial NCT02135926: Thrombectomy in Patients Ineligible for iv tPA
Official title: Comparison of Thrombectomy and Standard Care for Ischemic Stroke in Patients Ineligibility for Tissue Plasminogen Activator Treatment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Ischemic Stroke
Keywords: Cerebral Stroke, Stroke, Acute, Brain Infarction
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
Collaborators: name: University Hospital, Aachen
name: University Hospital Augsburg
name: Vivantes Krankenhaus Berlin Neukölln
name: Ruhr University of Bochum
name: Klinikum Dortmund Wirbelsäulenchirurgie
name: University of Erlangen-Nürnberg Medical School
name: Alfried Krupp Krankenhaus
name: University Hospital, Essen
name: University Hospital Freiburg
name: University Medical Center Goettingen
name: Universitätsklinikum Hamburg-Eppendorf
name: Universitätsklinik für Neurologie, Innsbruck
name: Universitätsklinikum Köln
name: The Wagner-Jauregg Provincial Neuropsychiatric Clinic
name: LMU Klinikum
name: Klinikum rechst der Isar Technische Universitaet Muenchen
name: KLINIKUM VEST Recklinghausen
name: Wuerzburg University Hospital
name: Asklepios Kliniken Hamburg GmbH
First posted: 2014-05-12
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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").

Eligibility criteria: 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.

Primary outcomes:
measure: mRS Shift
timeFrame: 90 (+/-14) days after treatment
Secondary outcomes:
measure: Neurological outcome
timeFrame: 90 (+/- 14) days after treatment
measure: Health Status
timeFrame: 90 (+/-14) days after treatment
measure: Infarct volume
timeFrame: 30 (-/+ 6) hours after treatment
measure: Successful Recanalization
timeFrame: 30 (-/+ 6) hours after treatment
Other outcomes:
measure: Safety endpoints
timeFrame: within 90 (+/- 14) days after treatment
Locations:
city: Linz
country: Austria
facility: Institut für Radiologie Oö. Gesundheits- und Spitals-AG Landes-Nervenklinik Wagner-Jauregg
city: Aachen
country: Germany
facility: Klinik für Diagnostische und Interventionelle Neuroradiologie Universitätsklinikum Aachen
city: Berlin
country: Germany
facility: Klinische und interventionelle Neuroradiologie Vivantes Klinikum Neukölln
city: Bochum
country: Germany
facility: Institut für Diagnostische und Interventionelle Radiologie, Neuroradiologie und Nuklearmedizin Universitätsklinikum Knappschaftskrankenhaus Bochum
city: Bochum
country: Germany
facility: University Clinic Bochum
city: Dortmund
country: Germany
facility: Kinik für Radiologie und Neuroradiologie
city: Erlangen
country: Germany
facility: Abteilung für Neuroradiologie Universitätsklinikum Erlangen
city: Essen
country: Germany
facility: Klinik für Radiologie und Neuroradiologie Alfried Krupp Krankenhaus
city: Essen
country: Germany
facility: Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie Universitätsklinikum Essen
city: Freiburg
country: Germany
facility: Klinik für Neuroradiologie Universitätsklinikum Freiburg
city: Goettingen
country: Germany
facility: Institut für Diagnostische & Interventionelle Neuroradiologie Universitätsmedizin Göttingen
city: Hamburg
country: Germany
facility: Klinik und Poliklinik für Neuroradiologische Diagnostik und Intervention
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Heidelberg
country: Germany
facility: Universität Heidelberg, Neuroradiologie
city: Köln
country: Germany
facility: Diagnostik , Neuroradiologie, Universitätsklinikum Köln
city: München
country: Germany
facility: Abteilung für Neuroradiologie Klinikum der Universität München Campus
city: München
country: Germany
facility: Abteilung für Diagnostische & Interventionelle Neuroradiogie Klinikum rechts der Isar der TU München
city: Recklinghausen
country: Germany
facility: Klinik für Radiologie, Neuroradiologie und Nuklearmedizin Behandlungszentrum Knappschaftskrankenhaus Recklinghausen
city: Würzburg
country: Germany
facility: Abteilung für Neuroradiologie Universitätsklinikum Würzburg
Study officials:
affiliation: University Hospital Heidelberg
name: Martin Bendszus, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.
citation: 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.