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Efficacy and Safety of Thrombectomy in Stroke With Extended Lesion and Extended Time Window (Tension)

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ClinicalTrials.gov Identifier: NCT03094715
Recruitment Status : Recruiting
First Posted : March 29, 2017
Last Update Posted : April 29, 2019
Sponsor:
Collaborators:
Karolinska University Hospital
Eppdata GmbH Hamburg, Germany
Aarhus University Hospital
Medical University Innsbruck
Groupe Hospitalier Pitie-Salpetriere
Oslo University Hospital
University Hospital, Martin
Charles University, Czech Republic
Hospices Civils de Lyon
CHU de Reims
Epidemiological and Clinical Research Information Network
STROKE ALLIANCE FOR EUROPE
INTERNATIONAL CONSORTIUM FOR HEALTHOUTCOMES MEASUREMENT INC.
Europan Society for Minimally Invasive Neurological Therapy
Universitätsklinikum Hamburg-Eppendorf
Information provided by (Responsible Party):
Martin Bendszus, University Hospital Heidelberg

Brief Summary:
TENSION (Efficacy and safety of ThrombEctomy iN Stroke with extended leSION and extended time window) is a prospective, open label, blinded endpoint (PROBE), European two-arm, randomized, controlled, post-market study to compare the safety and effectiveness of endovascular thrombectomy as compared to best medical care alone in the treatment of acute ischemic stroke patients with extended stroke lesions defined by an Alberta Stroke Program Early CT Score (ASPECTS) score of 3-5 and in an extended time window (up to 12 hours or unknown time of symptom onset). Up to 714 subjects will be randomized. Primary endpoint will be functional outcome assessed by the modified Rankin scale at 90 days post-stroke ("mRS shift analysis"). By this, TENSION will provide evidence of efficacy and safety of thrombectomy in an acute stroke population with uncertain benefit of endovascular stroke treatment.

Condition or disease Intervention/treatment Phase
Stroke, Acute Cerebral Stroke Cerebrovascular Stroke Apoplexy; Brain Device: Thrombectomy Other: Best medical care Not Applicable

Detailed Description:

This study is a prospective, open label, blinded endpoint (PROBE),European, two-arm, randomized, controlled, post-market study to compare the safety and effectiveness of endovascular thrombectomy as compared to best medical care alone in the treatment of acute ischemic stroke (AIS) in patients with extended stroke lesions defined by an ASPECT score of 3-5 and in an extended time window (up to 12 hours, or unknown time of symptom onset). This is an adaptive design study, with prospectively stated interim analyses with specified stopping rules allowing for the possibility early termination based on either a determination of study success or futility.

Up to 714 subjects will be enrolled in the study and randomized for the Intention to treat analysis set. The randomization will be stratified by time from symptom onset (0-6h and 6-11h/wake up stroke), and stroke severity (NIHSS ≤18, NIHSS >18).

Interim data analysis is planned after the primary endpoint has been obtained for one third and two thirds of the patients. At each of these sample sizes, the available 90-day mRS data for each treatment arm will be evaluated. Safety interim analysis will be performed after one third and two thirds of the patients have been included.

Subjects who meet the inclusion criteria will be randomized in a 1:1 ratio to one of the following two treatment arms:

Arm 1: best medical care Arm 2: endovascular thrombectomy and best medical care The primary objective of this study is to test efficacy and safety of thrombectomy in acute stroke patients with uncertain benefit of endovascular stroke treatment, i.e. extended ischemic lesion size with an ASPECT score of 3-5 or late (up to 12 hours) or unknown time window as compared to best medical care alone.

Approximately 40 sites in Up to 20 sites in 8-10 European countries Patients presenting with acute ischemic stroke (AIS) based on focal occlusion in the M1 segment of the middle cerebral artery (MCA), and/or the intracranial segment of the distal internal carotid artery (ICA), determined by Magnetic Resonance Angiography (MRA) or Computed Tomographic Angiography (CTA), and who meet all eligibility criteria will be considered for study enrollment.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 714 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: prospective, open label, blinded endpoint (PROBE), European, two-arm, randomized, controlled, post-market study
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Thrombectomy in Stroke With Extended Lesion and Extended Time Window: a Randomized, Controlled Trial
Actual Study Start Date : June 20, 2018
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : September 30, 2022

Arm Intervention/treatment
Active Comparator: Thrombectomy
Endovascular thrombectomy and best medical care
Device: Thrombectomy
Mechanical thrombectomy with state of the art thrombectomy devices (i.e. stent-retrievers, aspiration catheters). Devices will be used per instructions for use (IFU).
Other Name: Mechanical thrombectomy

Best medical care
Best medical treatment
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.). If applicable, the reason for iv tissue plasminogen activator (tPA) ineligibility has to be documented on the eCRF.
Other Name: Control group




Primary Outcome Measures :
  1. Clinical outcome-modified Rankin Scale at 90 days [ Time Frame: 90 days ]
    The primary endpoint of the trial is the modified Rankin Scale (mRS) outcome at 90 days post-stroke. The primary effectiveness endpoint analysis is a chi-square test of the difference in linear trends in ordinal mRS outcomes at 90 days post-procedure between treatment groups ("mRS shift analysis").


Secondary Outcome Measures :
  1. Independence - modified Rankin Scale≤2 at 90 days [ Time Frame: 90 days ]
    Independent neurological outcomes with 90-day mRS≤2

  2. Moderate Outcome - modified Rankin Scale≤3 at 90 days [ Time Frame: 90 days ]
    Moderate neurological outcome with 90-day mRS≤3

  3. Infarct volume 24 hours post procedure [ Time Frame: 18-36 hours ]
    Infarct volume at 24 hours on post-procedure imaging

  4. Infarct growth [ Time Frame: 18-36 hours ]
    Difference of infarct volume from infarct volume as predicted by pre-treatment imaging

  5. Functional neurological outcome at 12 months - modified Rankin Scale [ Time Frame: 12 month ]
    Functional neurological outcome at 12 months (±14 days) after stroke (simplified modified Rankin Scale questionnaire, smRSq)

  6. Quality of life - PROMIS-10 [ Time Frame: 90 days ]
    Patient-Reported Outcomes Measurement Information System (PROMIS)-10 questionaire at 90 (±14) days. PROMIS Global-10 short form consists of 10 items that assess general domains of health and functioning including overall physical health, mental health, social health, pain, fatigue, and overall perceived quality of life.

  7. Quality of life - EQ-5D [ Time Frame: 90 days ]
    Patient-reported functional health status and quality of life 90 (±14) days. EuroQol five-dimension scale. A standardised instrument created by the EuroQol Group as a measure of health outcome. EQ-5D is a descriptive system of health-related quality of life states consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each of which can take one of three responses reflecting severity (no problems/some or moderate problems/extreme problems).

  8. Post-stroke depression - Patient Health Questionnaire-4 [ Time Frame: 90 days ]
    Post-stroke depression 90 (±14) days after stroke based on the Patient Health Questionnaire-4 (PHQ-4), Patient Health Questionnaire-4, Psychological distress in PHQ-4 is being rated based on 4 questions as none (0-2") mild (3-5) moderate (6-8) severe (9-12)

  9. Parenchymal hemorrhage type 2 [ Time Frame: 90 days ]
    blood clots in >30% of the infarcted area with a substantial space-occupying effect.

  10. modified Rankin Scale between 4-6 [ Time Frame: 12 month ]
    Death or dependency

  11. Frequencies of Adverse Events (AE) in both treatment arms within the first 7 days [ Time Frame: 7 days ]

    Serious AEs (SAEs), overall (all-cause mortality) and stroke-related death (i.e., related to intracranial bleeding, midline shift, brain herniation, progression of stroke symptoms, or systemic complications from stroke such as pneumonia).

    • Space-occupying infarction (malignant brain edema)
    • New ischemic stroke

  12. Serious AEs [ Time Frame: 12 month ]
    Serious AEs (SAEs), overall (all-cause mortality) and stroke-related death (i.e., related to intracranial bleeding, midline shift, brain herniation, progression of stroke symptoms, or systemic complications from stroke such as pneumonia).

  13. Space-occupying infarction [ Time Frame: 18-36 hours ]
    Malignant brain edema after treatment

  14. New ischemic stroke [ Time Frame: 12 month ]
    New AIS after treatment

  15. Symptomatic intracranial hemorrhage (sICH) at 24 (18-36) hours (CT or MRI) [ Time Frame: 18-36 hours ]

    sICH as defined in Safe Implementation of Treatments in Stroke-Monitoring Study (SITS-MOST)

    • parenchymal hemorrhage type 2 (PH-2)
    • Frequencies of Adverse Events (AE) in both treatment arms within the first 7 days after treatment
    • Serious AEs (SAEs), overall (all-cause mortality) and stroke-related death (i.e., related to intracranial bleeding, midline shift, brain herniation, progression of stroke symptoms, or systemic complications from stroke such as pneumonia).
    • Space-occupying infarction (malignant brain edema)
    • New ischemic stroke

  16. Cost Utility Assessment [ Time Frame: 12 month ]
    Assessment of costs from the time of randomization to the 12-months follow-up, including costs of hospitalization, institutionalized living, outpatient care, informal care provided by relatives and cost of lost productivity

  17. Quality of life - PROMIS-10 [ Time Frame: 12 month ]
    Patient-Reported Outcomes Measurement Information System (PROMIS)-10 questionaire at 12 month (±14 days). PROMIS Global-10 short form consists of 10 items that assess general domains of health and functioning including overall physical health, mental health, social health, pain, fatigue, and overall perceived quality of life.

  18. Quality of life - EQ-5D [ Time Frame: 12 month ]
    Health related quality of life assessment at 12 months (±14 days). EuroQol five-dimension scale. A standardised instrument created by the EuroQol Group as a measure of health outcome. EQ-5D is a descriptive system of health-related quality of life states consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each of which can take one of three responses reflecting severity (no problems/some or moderate problems/extreme problems).

  19. Post-stroke depression - Patient Health Questionnaire-4 [ Time Frame: 12 month ]
    Health related quality of life assessment at 12 months (±14 days) to assess post stroke depression - Patient Health Questionnaire-4 (PHQ-4) Psychological distress in PHQ-4 is being rated based on 4 questions as none (0-2") mild (3-5) moderate (6-8) severe (9-12)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Randomization within 11 hours after stroke onset (if known) or last seen well.
  • Endovascular treatment is expected to be finished within 12 hours after known symptom onset or last seen well by judgment of the interventional neuroradiologist in charge (if stroke onset is known).
  • 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 above 18 up to 80 years of age
  • NIHSS Score of <26
  • Signed informed consent (IC) form by patient or legal guardian, or inclusion of patient's presumptive will by investigator under emergency situation, but after consultation of an independent physician who is familiar with these types of illness if the other options are not possible according to local approval.
  • Prior to new focal neurological deficit, mRS score was ≤2.

Imaging Inclusion Criteria

  • 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).
  • CT (non-contrast CT) or DWI with an ASPECT score of 3-5

Clinical exclusion criteria

  • 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 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
  • Patient's anticipated life expectancy is less than 6 Months12 months

Imaging exclusion criteria

  • ExtracaranialExtracranial CT scan or MR angiography showing high grade stenosis expected to require acute stent placement (especially e.g. ICAACI stenting) during the procedure to get access to the occlusion
  • CT or MRI with evidence of: Mass mass effect or intracranial tumor, or hypodensity on unenhanced CT and
  • If CT perfusion is done per institutional standard: CBV drop on CBV maps on CTP, or, alternatively as with an ASPECT score of 0-2
  • If DWI is done per institutional standard,: restricted diffusion on DWI with an ASPECT score of 0-2, or above 5

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03094715


Contacts
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Contact: Susanne Bonekamp, DVM, PhD +49 6221 5635710 susanne.bonekamp@med.uni-heidelberg.de
Contact: Sylvia P Danner +49 6221 56-35197 SylviaPatricia.Danner@med.uni-heidelberg.de

  Show 37 Study Locations
Sponsors and Collaborators
University Hospital Heidelberg
Karolinska University Hospital
Eppdata GmbH Hamburg, Germany
Aarhus University Hospital
Medical University Innsbruck
Groupe Hospitalier Pitie-Salpetriere
Oslo University Hospital
University Hospital, Martin
Charles University, Czech Republic
Hospices Civils de Lyon
CHU de Reims
Epidemiological and Clinical Research Information Network
STROKE ALLIANCE FOR EUROPE
INTERNATIONAL CONSORTIUM FOR HEALTHOUTCOMES MEASUREMENT INC.
Europan Society for Minimally Invasive Neurological Therapy
Universitätsklinikum Hamburg-Eppendorf
Investigators
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Study Chair: Götz Thomalla, MD Coordination and Project Management Tension, Neurology, UKE Hamburg, Germany
Principal Investigator: Martin Bendszus, MD Central Trial Management Tension, Neuroradiology, UHHeidelberg, Germany

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Martin Bendszus, Central trial management, Coordinating investigator, University Hospital Heidelberg
ClinicalTrials.gov Identifier: NCT03094715     History of Changes
Other Study ID Numbers: TENSION
First Posted: March 29, 2017    Key Record Dates
Last Update Posted: April 29, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Martin Bendszus, University Hospital Heidelberg:
Mechanical thrombectomy
Endovascular thrombectomy
Additional relevant MeSH terms:
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Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases