Thrombectomy in Patients Ineligible for iv tPA

NCT02135926 | Terminated DMC

• 2 other identifiers: UH-Heidelberg-THRILLDRKS00005792
• Study Type: interventional
• Target: 4
• Locations: 2 countries
• Sites: 19

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.

Conditions

Ischemic Stroke

Keywords

Cerebral Stroke, Stroke, Acute, Brain Infarction

Outcome Measures

Primary Outcomes (1)

• 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 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.

  90 (+/-14) days after treatment

Secondary Outcomes (4)

• Neurological outcome

  90 (+/- 14) days after treatment

• Health Status

  90 (+/-14) days after treatment

• Infarct volume

  30 (-/+ 6) hours after treatment

• Successful Recanalization

  30 (-/+ 6) hours after treatment

Other Outcomes (1)

• Safety endpoints

  within 90 (+/- 14) days after treatment

Study Arms (2)

Best medical care

ACTIVE COMPARATOR

Best clinical care in dedicated stroke unit

Other: Best medical care

Thrombectomy

ACTIVE COMPARATOR

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).

Device: Thrombectomy

Interventions

Thrombectomy 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.

Also known as: Stent Retrievers, Solitaire (Covidien), Trevo (Stryker)

Thrombectomy

Best medical care 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.).

Also known as: clinical care, conservative treatment

Best medical care

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (19)

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

Linz, 4020, Austria

Location

Klinik für Diagnostische und Interventionelle Neuroradiologie Universitätsklinikum Aachen

Aachen, 52074, Germany

Location

Klinische und interventionelle Neuroradiologie Vivantes Klinikum Neukölln

Berlin, 12351, Germany

Location

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

Bochum, 44892, Germany

Location

University Clinic Bochum

Bochum, Germany

Location

Diagnostik , Neuroradiologie, Universitätsklinikum Köln

Cologne, 50937, Germany

Location

Kinik für Radiologie und Neuroradiologie

Dortmund, 44137, Germany

Location

Abteilung für Neuroradiologie Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

Klinik für Radiologie und Neuroradiologie Alfried Krupp Krankenhaus

Essen, 45131, Germany

Location

Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie Universitätsklinikum Essen

Essen, 45147, Germany

Location

Klinik für Neuroradiologie Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Institut für Diagnostische & Interventionelle Neuroradiologie Universitätsmedizin Göttingen

Göttingen, 37075, Germany

Location

Klinik und Poliklinik für Neuroradiologische Diagnostik und Intervention

Hamburg, 20246, Germany

Location

Asklepios Klinik Altona

Hamburg, 22763, Germany

Location

Universität Heidelberg, Neuroradiologie

Heidelberg, 69120, Germany

Location

Abteilung für Neuroradiologie Klinikum der Universität München Campus

München, 81377, Germany

Location

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

München, 81675, Germany

Location

Klinik für Radiologie, Neuroradiologie und Nuklearmedizin Behandlungszentrum Knappschaftskrankenhaus Recklinghausen

Recklinghausen, 45657, Germany

Location

Abteilung für Neuroradiologie Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Related Publications (7)

• 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.

  PMID: 18388338 BACKGROUND

• 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.

  PMID: 22932714 BACKGROUND

• 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.

  PMID: 19590057 BACKGROUND

• 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.

  PMID: 22932715 BACKGROUND

• 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.

  PMID: 21852620 BACKGROUND

• 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.

  PMID: 26275228 DERIVED

• 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.

  PMID: 26044962 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Stroke; Brain Infarction

Interventions

Thrombectomy; Conservative Treatment

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Ischemia; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Therapeutics

Study Officials

• Martin Bendszus, MD

  University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Martin Bendszus

Study Record Dates

• First Submitted: April 30, 2014
• First Posted: May 12, 2014
• Study Start: March 1, 2014
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: June 7, 2018

Record last verified: 2018-06

Locations

AU (1); DE (18)