Clinical trial NCT03094715: Efficacy and Safety of Thrombectomy in Stroke With Extended Lesion and Extended Time Window
Official title: Efficacy and Safety of Thrombectomy in Stroke With Extended Lesion and Extended Time Window: a Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Stroke, Acute
Cerebral Stroke
Cerebrovascular Stroke
Apoplexy; Brain
Keywords: Mechanical thrombectomy
Endovascular thrombectomy
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
Collaborators: name: Karolinska University Hospital
name: Eppdata GmbH Hamburg, Germany
name: Aarhus University Hospital
name: Medical University Innsbruck
name: Groupe Hospitalier Pitie-Salpetriere
name: Oslo University Hospital
name: University Hospital, Martin
name: Charles University, Czech Republic
name: Hospices Civils de Lyon
name: CHU de Reims
name: Epidemiological and Clinical Research Information Network
name: STROKE ALLIANCE FOR EUROPE
name: International Consortium for Health Outcome Measurement, Inc.
name: Europan Society for Minimally Invasive Neurological Therapy
name: Universitätsklinikum Hamburg-Eppendorf
First posted: 2017-03-29
Enrollment: 253
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, open label, blinded endpoint (PROBE), European, two-arm, randomized, controlled, post-market study
Primary purpose: TREATMENT

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 665 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.

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 665 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.

Eligibility 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 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

Primary outcomes:
measure: Clinical outcome-modified Rankin Scale at 90 days
timeFrame: 90 days
Secondary outcomes:
measure: Independence - modified Rankin Scale≤2 at 90 days
timeFrame: 90 days
measure: Moderate Outcome - modified Rankin Scale≤3 at 90 days
timeFrame: 90 days
measure: Infarct volume 24 hours post procedure
timeFrame: 18-36 hours
measure: Infarct growth
timeFrame: 18-36 hours
measure: Functional neurological outcome at 12 months - modified Rankin Scale
timeFrame: 12 month
measure: Quality of life - PROMIS-10
timeFrame: 90 days
measure: Quality of life - EQ-5D
timeFrame: 90 days
measure: Post-stroke depression - Patient Health Questionnaire-4
timeFrame: 90 days
measure: Parenchymal hemorrhage type 2
timeFrame: 90 days
measure: modified Rankin Scale between 4-6
timeFrame: 12 month
measure: Frequencies of Adverse Events (AE) in both treatment arms within the first 7 days
timeFrame: 7 days
measure: Serious AEs
timeFrame: 12 month
measure: Space-occupying infarction
timeFrame: 18-36 hours
measure: New ischemic stroke
timeFrame: 12 month
measure: Symptomatic intracranial hemorrhage (sICH) at 24 (18-36) hours (CT or MRI)
timeFrame: 18-36 hours
measure: Cost Utility Assessment
timeFrame: 12 month
measure: Quality of life - PROMIS-10
timeFrame: 12 month
measure: Quality of life - EQ-5D
timeFrame: 12 month
measure: Post-stroke depression - Patient Health Questionnaire-4
timeFrame: 12 month
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University Graz
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
city: Linz
country: Austria
facility: Neuroradiology, Keppler University Hospital Linz
city: Salzburg
country: Austria
facility: Department of Neurology, Reseach Institute of Neurointervention, Christian Doppler Clinic, Paracelsus Medical University Salzburg
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Brno
country: Czechia
facility: St. Anne's University Hospital Brno
city: Hradec Kralove,
country: Czechia
facility: Faculty Hospital Hradec Kralove
city: Ostrava
country: Czechia
facility: Comprehensive stroke center,University Hospital Ostrava
city: Prague
country: Czechia
facility: Homolka Hospital Prague
city: Usti nad Labem
country: Czechia
facility: Dept. of Radiology, Masaryk hospital
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: University Hospital Rigshospitalet
city: Clermont-Ferrand
country: France
facility: CHU Gabriel Montpied, Clermont-Ferrand
city: Le Kremlin-Bicêtre
country: France
facility: Hôpiteaux Universitaires Paris-Sud, Hôpital Bicêtre
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
city: Reims
country: France
facility: Université Reims Champagne Ardenne/ Department of Neuroradiology, Hôpital Maison Blanche
city: Rennes
country: France
facility: CHU de Rennes/Centre Urgences-Réanimations
city: Tours
country: France
facility: CHRU Hôpiteaux de Tours / Hôpital Bretonneau
city: Minden
country: Germany
facility: Universitätsinstitut für Diagnostische Radiologie, Neuroradiologie und Nuklearmedizin Johannes Wesling Klinikum Minden
state: Nordrhein-Westfalen
city: Magdeburg
country: Germany
facility: Otto-von-Guericke-University Magdeburg
state: Sachsen-Anhalt
city: Bochum
country: Germany
facility: Universitätsklinikum KK Bochum-Langendreer Institut für Diagnostische und Interventionelle Radiologie, Neuroradiologie und Nuklearmedizin
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Bremen
country: Germany
facility: Gesundheit Nord gGmbH Klinikverbund Bremen
city: Dortmund
country: Germany
facility: Klinik für Radiologie und Neuroradiologie am Klinikum Mitte
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
city: Essen
country: Germany
facility: Alfried Krupp Krankenhaus Rüttenscheid
city: Flensburg
country: Germany
facility: Diakonissenkrankenhaus Flensburg
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: Neuroradiologie Universitätsklinikum Heidelberg
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig AöR
city: Lübeck
country: Germany
facility: UKSH Universitätsklinikum Schleswig-Holstein Campus Lübeck
city: München
country: Germany
facility: Klinikum der Universität München
city: München
country: Germany
facility: Technische Universität München / Klinikum rechts der Isar
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Tromsø
country: Norway
facility: The Arctic University of Norway
city: Martin
country: Slovakia
facility: Comenius University's Jessenius Faculty of Medicine and University Hospital
city: Trnava
country: Slovakia
facility: Faculty Hospital Trnava
city: Madrid
country: Spain
facility: La Paz University Hospital
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: Coordination and Project Management Tension, Neurology, UKE Hamburg, Germany
name: Götz Thomalla, MD
role: STUDY_CHAIR
affiliation: Central Trial Management Tension, Neuroradiology, UHHeidelberg, Germany
name: Martin Bendszus, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bendszus M, Bonekamp S, Berge E, Boutitie F, Brouwer P, Gizewski E, Krajina A, Pierot L, Randall G, Simonsen CZ, Zelenak K, Fiehler J, Thomalla G. A randomized controlled trial to test efficacy and safety of thrombectomy in stroke with extended lesion and extended time window. Int J Stroke. 2019 Jan;14(1):87-93. doi: 10.1177/1747493018798558. Epub 2018 Aug 29.
citation: Bendszus M, Fiehler J, Subtil F, Bonekamp S, Aamodt AH, Fuentes B, Gizewski ER, Hill MD, Krajina A, Pierot L, Simonsen CZ, Zelenak K, Blauenfeldt RA, Cheng B, Denis A, Deutschmann H, Dorn F, Flottmann F, Gellissen S, Gerber JC, Goyal M, Haring J, Herweh C, Hopf-Jensen S, Hua VT, Jensen M, Kastrup A, Keil CF, Klepanec A, Kurca E, Mikkelsen R, Mohlenbruch M, Muller-Hulsbeck S, Munnich N, Pagano P, Papanagiotou P, Petzold GC, Pham M, Puetz V, Raupach J, Reimann G, Ringleb PA, Schell M, Schlemm E, Schonenberger S, Tennoe B, Ulfert C, Valis K, Vitkova E, Vollherbst DF, Wick W, Thomalla G; TENSION Investigators. Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial. Lancet. 2023 Nov 11;402(10414):1753-1763. doi: 10.1016/S0140-6736(23)02032-9. Epub 2023 Oct 11.
citation: van Horn N, Kniep H, Broocks G, Meyer L, Flottmann F, Bechstein M, Gotz J, Thomalla G, Bendszus M, Bonekamp S, Pfaff JAR, Dellani PR, Fiehler J, Hanning U. ASPECTS Interobserver Agreement of 100 Investigators from the TENSION Study. Clin Neuroradiol. 2021 Dec;31(4):1093-1100. doi: 10.1007/s00062-020-00988-x. Epub 2021 Jan 27.
citation: Roaldsen MB, Jusufovic M, Berge E, Lindekleiv H. Endovascular thrombectomy and intra-arterial interventions for acute ischaemic stroke. Cochrane Database Syst Rev. 2021 Jun 14;6(6):CD007574. doi: 10.1002/14651858.CD007574.pub3.