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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University Hospital Heidelberg
Sponsor:
Collaborators:
University Hospital, Aachen
Klinikum Augsburg
Vivantes Krankenhaus Berlin Neukölln
Knappschaftskrankenhaus Ruhr University of Bochum
Klinikum Dortmund gGmbH
University of Erlangen-Nürnberg Medical School
Alfried Krupp Krankenhaus Essen
University Hospital, Essen
University Hospital Freiburg
University Medical Center Goettingen
Universitätsklinikum Hamburg-Eppendorf
Universitätsklinik für Neuroradiologie Innsbruck
Universitätsklinikum Köln
Nervenklinik Linz
Klinikum der Universitaet Muenchen
Klinikum rechst der Isar Technische Universitaet Muenchen
KLINIKUM VEST Recklinghausen
Wuerzburg University Hospital
Asklepios Kliniken Hamburg GmbH
Information provided by (Responsible Party):
Susanne Bonekamp, University Hospital Heidelberg
ClinicalTrials.gov Identifier:
NCT02135926
First received: April 30, 2014
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention
Ischemic Stroke
Device: Thrombectomy
Other: Best medical care

Study Type: Interventional
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

Further study details as provided by University Hospital Heidelberg:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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


Estimated Enrollment: 600
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)
Arms Assigned Interventions
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.).
Other Names:
  • clinical care
  • conservative treatment
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).
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 Names:
  • Stent Retrievers
  • Solitaire (Covidien)
  • Trevo (Stryker)

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02135926

Contacts
Contact: Martin Bendszus, MD +496221 567566 Martin.Bendszus@med.uni-heidelberg.de
Contact: Susanne Bonekamp, PhD +496221 5635710 susanne.bonekamp@med.uni-heidelberg.de

Locations
Austria
Institut für Radiologie Oö. Gesundheits- und Spitals-AG Landes-Nervenklinik Wagner-Jauregg Not yet recruiting
Linz, Austria, 4020
Contact: Johannes Trenkler, MD       johannes.trenkler@gespag.at   
Contact: Karin Nussbaumer       karin.nussbaumer@gespag.at   
Sub-Investigator: Karin Nussbaumer, MD         
Principal Investigator: Johannes Trenkler, MD         
Sub-Investigator: Hans-Peter Haring, MD         
Germany
Klinik für Diagnostische und Interventionelle Neuroradiologie Universitätsklinikum Aachen Not yet recruiting
Aachen, Germany, 52074
Contact: Martin Wiesmann, MD       mwiesmann@ukaachen.de   
Contact: Daniela Probst       dprobst@ukaachen.de   
Principal Investigator: Martin Wiesmann, MD         
Klinische und interventionelle Neuroradiologie Vivantes Klinikum Neukölln Recruiting
Berlin, Germany, 12351
Contact: Alexander Bock, MD       alexander.bock@vivantes.de   
Contact: Boris Dimitrijeski, MD       boris.dimitrijeski@vivantes.de   
Principal Investigator: Alexander Bock, MD         
Sub-Investigator: Boris Dimitrijeski, MD         
Institut für Diagnostische und Interventionelle Radiologie, Neuroradiologie und Nuklearmedizin Universitätsklinikum Knappschaftskrankenhaus Bochum Not yet recruiting
Bochum, Germany, 44892
Contact: Annika Kowoll       akowoll@googlemail.com   
Contact: Werner Weber, MD       werner.weber@kk-bochum.de   
Principal Investigator: Werner Weber, MD         
Sub-Investigator: Jens Eyding, MD         
Kinik für Radiologie und Neuroradiologie Recruiting
Dortmund, Germany, 44137
Contact: Sibylle Ademi       sibylle.ademi@klinikumdo.de   
Contact: Alexander Ranft, MD       alexander.ranft@klinikumdo.de   
Principal Investigator: Stefan Thode, MD         
Sub-Investigator: Alexander Ranft, MD         
Sub-Investigator: Gernot Rudel, MD         
Abteilung für Neuroradiologie Universitätsklinikum Erlangen Recruiting
Erlangen, Germany, 91054
Contact: Tobias Engelhorn, MD       neuroradiologie@uk-erlangen.de   
Contact: Martina Weibart, MSc       Marina.Weibart@uk-erlangen.de   
Principal Investigator: Tobias Engelhorn, MD         
Sub-Investigator: Martin Köhrmann, MD         
Sub-Investigator: Arnd Dörfler, MD         
Klinik für Radiologie und Neuroradiologie Alfried Krupp Krankenhaus Not yet recruiting
Essen, Germany, 45131
Contact: Nicole Müller       Nicole.Mueller@krupp-krankenhaus.de   
Contact: Rene Chapot, MD       neuroradiologie@krupp-krankenhaus.de   
Principal Investigator: Rene Chapot, MD         
Sub-Investigator: Peter Berlit, MD         
Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie Universitätsklinikum Essen Not yet recruiting
Essen, Germany, 45147
Contact: Sabrina Keil, PhD       Sabrina.Keil@uk-essen.de   
Contact: Michael Forsting, MD       michael.forsting@uk-essen.de   
Principal Investigator: Michael Forsting, MD         
Sub-Investigator: Marc Schlamann, MD         
Sub-Investigator: Christian Weimar, MD         
Klinik für Neuroradiologie Universitätsklinikum Freiburg Not yet recruiting
Freiburg, Germany, 79106
Contact: Ulrike Bergmann       ulrike.bergmann@uniklinik-freiburg.de   
Contact: Horst Urbach, MD       horst.urbach@uniklinik-freiburg.de   
Principal Investigator: Horst Urbach, MD         
Sub-Investigator: Christian Taschner, MD         
Institut für Diagnostische & Interventionelle Neuroradiologie Universitätsmedizin Göttingen Not yet recruiting
Goettingen, Germany, 37075
Contact: Annika Richter       a.richter@med.uni-goettingen.de   
Contact: Marios Nikos Psychogios, MD       m.psychogios@med.uni-goettingen.de   
Sub-Investigator: Marios Nikos Psychogios, MD         
Principal Investigator: Michael Knauth, MD         
Klinik und Poliklinik für Neuroradiologische Diagnostik und Intervention Recruiting
Hamburg, Germany, 20246
Contact: Jens Fiehler, MD       fiehler@uke.de   
Contact: Jan-Hendrik Buhk, MD       j.buhk@uke.de   
Sub-Investigator: Jan-Hendrik Buhk, MD         
Principal Investigator: Jens Fiehler, MD         
Sub-Investigator: Andre Kemmling, MD         
Sub-Investigator: Götz Thomalla, MD         
Asklepios Klinik Altona Recruiting
Hamburg, Germany, 22763
Contact: Bernd Eckert, MD    ++49401818818527    b.eckert@asklepios.com   
Contact: Felix Kaemmerer, MD       f.kaemmerer@asklepios.com   
Principal Investigator: Bernd Eckert, MD         
Sub-Investigator: Felix Kämmerer, MD         
Sub-Investigator: Joachim Röther, MD         
Universität Heidelberg, Neuroradiologie Recruiting
Heidelberg, Germany, 69120
Contact: Susanne Bonekamp, PhD    ++4962215635710    susanne.bonekamp@med.uni-heidelberg.de   
Contact: Martin Bendszus, MD    ++496221567566    thrill@med.uni-heidelberg.de   
Principal Investigator: Martin Bendszus, MD         
Sub-Investigator: Peter A Ringleb, MD         
Sub-Investigator: Oliver Menn, MD         
Sub-Investigator: Jan Purrucker, MD         
Sub-Investigator: Markus Moehlenbruch, MD         
Sub-Investigator: Mirko Pham, MD         
Sub-Investigator: Christian Herweh, MD         
Sub-Investigator: Christoph Gumbinger, MD         
Klinik für Radiologie und Neuroradiologie Universitätsklinikum Schleswig-Holstein Campus Kiel Not yet recruiting
Kiel, Germany, 24105
Contact: Susanne Becke       Susanne.Becke@uksh.de   
Contact: Sabine Krieter       s.krieter@rad.uni-kiel.de   
Principal Investigator: Olav Jansen, MD         
Diagnostik , Neuroradiologie, Universitätsklinikum Köln Not yet recruiting
Köln, Germany, 50937
Contact: Silke Vent       silke.vent@uk-koeln.de   
Contact: Thomas Liebig, MD       thomas.liebig@uk-koeln.de   
Principal Investigator: Thomas Liebig, MD         
Sub-Investigator: Anastasios Mpostsaris, MD         
Sub-Investigator: Christoph Kabbasch, MD         
Sub-Investigator: Özgür Onur, MD         
Sub-Investigator: Christian Dohmen, MD         
Abteilung für Neuroradiologie Klinikum der Universität München Campus Not yet recruiting
München, Germany, 81377
Contact: Gunther Fesl, MD       Gunther.Fesl@med.uni-muenchen.de   
Contact: Klaus Jahn, MD       klaus.jahn@med.uni-muenchen.de   
Principal Investigator: Gunther Fesl, MD         
Sub-Investigator: Klaus Jahn, MD         
Sub-Investigator: Hartmut Brückmann, MD         
Abteilung für Diagnostische & Interventionelle Neuroradiogie Klinikum rechts der Isar der TU München Recruiting
München, Germany, 81675
Contact: Manuela Dietz       manuela.dietz@tum.de   
Contact: Claus Zimmer, MD       claus.zimmer@tum.de   
Principal Investigator: Claus Zimmer, MD         
Sub-Investigator: Tobias Boeckh-Behrens, MD         
Sub-Investigator: Silke Wunderlich, MD         
Sub-Investigator: Holger Poppert, MD         
Klinik für Radiologie, Neuroradiologie und Nuklearmedizin Behandlungszentrum Knappschaftskrankenhaus Recklinghausen Not yet recruiting
Recklinghausen, Germany, 45657
Contact: Annika Kowoll       akowoll@googlemail.com   
Contact: Werner Weber, MD       Werner.Weber@Klinikum-Vest.de   
Principal Investigator: Werner Weber, MD         
Sub-Investigator: Jens Eyding, MD         
Abteilung für Neuroradiologie Universitätsklinikum Würzburg Not yet recruiting
Würzburg, Germany, 97080
Contact: Christine Leypold       leypold_c@ukw.de   
Contact: László Solymosi, MD       solymosi_l@ukw.de   
Principal Investigator: László Solymosi, MD         
Sub-Investigator: György Homola, PhD         
Sub-Investigator: Christoph Kleinschnitz, MD         
Sponsors and Collaborators
University Hospital Heidelberg
University Hospital, Aachen
Klinikum Augsburg
Vivantes Krankenhaus Berlin Neukölln
Knappschaftskrankenhaus Ruhr University of Bochum
Klinikum Dortmund gGmbH
University of Erlangen-Nürnberg Medical School
Alfried Krupp Krankenhaus Essen
University Hospital, Essen
University Hospital Freiburg
University Medical Center Goettingen
Universitätsklinikum Hamburg-Eppendorf
Universitätsklinik für Neuroradiologie Innsbruck
Universitätsklinikum Köln
Nervenklinik Linz
Klinikum der Universitaet Muenchen
Klinikum rechst der Isar Technische Universitaet Muenchen
KLINIKUM VEST Recklinghausen
Wuerzburg University Hospital
Asklepios Kliniken Hamburg GmbH
Investigators
Principal Investigator: Martin Bendszus, MD University Hospital Heidelberg
  More Information

Additional Information:
Publications:

Responsible Party: Susanne Bonekamp, Prof. Dr. Martin Bendszus, University Hospital Heidelberg
ClinicalTrials.gov Identifier: NCT02135926     History of Changes
Other Study ID Numbers: UH-Heidelberg-THRILL, DRKS00005792
Study First Received: April 30, 2014
Last Updated: September 16, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Heidelberg:
Cerebral Stroke, Stroke, Acute, Brain Infarction

Additional relevant MeSH terms:
Stroke
Cerebral Infarction
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Pathologic Processes
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on September 18, 2014