Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has suspended participant recruitment.
(Recruitment is on hold until MR CLEAN, ESCAPE, EXTEND-IA, and SWIFt PRIME have been evaluated.)
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
Landes-Nervenklinik Wagner-Jauregg, 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: January 30, 2015
Last verified: January 2015
  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

Locations
Austria
Institut für Radiologie Oö. Gesundheits- und Spitals-AG Landes-Nervenklinik Wagner-Jauregg
Linz, Austria, 4020
Germany
Klinik für Diagnostische und Interventionelle Neuroradiologie Universitätsklinikum Aachen
Aachen, Germany, 52074
Klinische und interventionelle Neuroradiologie Vivantes Klinikum Neukölln
Berlin, Germany, 12351
Institut für Diagnostische und Interventionelle Radiologie, Neuroradiologie und Nuklearmedizin Universitätsklinikum Knappschaftskrankenhaus Bochum
Bochum, Germany, 44892
University Clinic Bochum
Bochum, Germany
Kinik für Radiologie und Neuroradiologie
Dortmund, Germany, 44137
Abteilung für Neuroradiologie Universitätsklinikum Erlangen
Erlangen, Germany, 91054
Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie Universitätsklinikum Essen
Essen, Germany, 45147
Klinik für Radiologie und Neuroradiologie Alfried Krupp Krankenhaus
Essen, Germany, 45131
Klinik für Neuroradiologie Universitätsklinikum Freiburg
Freiburg, Germany, 79106
Institut für Diagnostische & Interventionelle Neuroradiologie Universitätsmedizin Göttingen
Goettingen, Germany, 37075
Asklepios Klinik Altona
Hamburg, Germany, 22763
Klinik und Poliklinik für Neuroradiologische Diagnostik und Intervention
Hamburg, Germany, 20246
Universität Heidelberg, Neuroradiologie
Heidelberg, Germany, 69120
Diagnostik , Neuroradiologie, Universitätsklinikum Köln
Köln, Germany, 50937
Abteilung für Diagnostische & Interventionelle Neuroradiogie Klinikum rechts der Isar der TU München
München, Germany, 81675
Abteilung für Neuroradiologie Klinikum der Universität München Campus
München, Germany, 81377
Klinik für Radiologie, Neuroradiologie und Nuklearmedizin Behandlungszentrum Knappschaftskrankenhaus Recklinghausen
Recklinghausen, Germany, 45657
Abteilung für Neuroradiologie Universitätsklinikum Würzburg
Würzburg, Germany, 97080
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
Landes-Nervenklinik Wagner-Jauregg, 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: January 30, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

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

ClinicalTrials.gov processed this record on March 03, 2015