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

Conditions

Apoplexy; Brain, Cerebral Stroke, Cerebrovascular Stroke, Stroke, Acute

Keywords

Mechanical thrombectomy, Endovascular thrombectomy

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.

Schlemm E, Jensen M, Schell M, Fiehler J, Subtil F, Bonekamp S, Aamodt AH, Fuentes B, Gizewski ER, Hill MD, Krajina A, Pierot L, Simonsen CZ, Zeleňák K, Blauenfeldt RA, Denis A, Deutschmann H, Dorn F, Flottmann F, Gellißen S, Gerber JC, Goyal M, Haring J, Herweh C, Hopf-Jensen S, Hua VT, Kastrup A, Keil CF, Klepanec A, Kurča E, Meyer L, Mikkelsen R, Möhlenbruch M, Müller-Hülsbeck S, Münnich N, Pagano P, Papanagiotou P, Petzold GC, Pham M, Puetz V, Raupach J, Reimann G, Ringleb PA, Schönenberger S, Tennøe B, Ulfert C, Vališ K, Vítková E, Vollherbst DF, Wick W, Bendszus M, Cheng B, Thomalla G, TENSION Investigators *.

2026-06-09

10.1161/jaha.125.047192

Net Water Uptake at CT Predicts the Treatment Effect of Thrombectomy for Low ASPECTS Stroke.

Broocks G, Bendszus M, Simonsen CZ, Thomalla G, Gizewski ER, Aamodt AH, Krajina A, Pierot L, Zeleňák K, Fuentes B, Hill MD, Kemmling A, Gellissen S, Fiehler J, Meyer L, Kniep H, TENSION investigators, Tension Investigators.

2025-11-011 citations

10.1148/radiol.250708

Arterial Collaterals and Endovascular Treatment Effect in Acute Ischemic Stroke with Large Infarct: A Secondary Analysis of the TENSION Trial.

Winkelmeier L, Kniep H, Thomalla G, Bendszus M, Subtil F, Bonekamp S, Aamodt AH, Fuentes B, Gizewski ER, Hill MD, Krajina A, Pierot L, Simonsen CZ, Zeleňák K, Blauenfeldt RA, Cheng B, Denis A, Deutschmann H, Dorn F, Gellissen S, Gerber JC, Goyal M, Haring J, Herweh C, Hopf-Jensen S, Hua VT, Jensen M, Kastrup A, Keil CF, Klepanec A, Kurča E, Mikkelsen R, Möhlenbruch M, Müller-Hülsbeck S, Münnich N, Pagano P, Papanagiotou P, Petzold GC, Pham M, Puetz V, Raupach J, Reimann G, Ringleb PA, Schell M, Schlemm E, Schönenberger S, Tennøe B, Ulfert C, Vališ K, Vítková E, Vollherbst DF, Wick W, Fiehler J, Flottmann F, TENSION Investigators.

2025-02-016 citations

10.1148/radiol.242401

Endovascular thrombectomy for acute ischaemic stroke with established large infarct (TENSION): 12-month outcomes of a multicentre, open-label, randomised trial.

Thomalla G, Fiehler J, Subtil F, Bonekamp S, Aamodt AH, Fuentes B, Gizewski ER, Hill MD, Krajina A, Pierot L, Simonsen CZ, Zeleňák 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, Kurča E, Mikkelsen R, Möhlenbruch M, Müller-Hülsbeck S, Münnich N, Pagano P, Papanagiotou P, Petzold GC, Pham M, Puetz V, Raupach J, Reimann G, Ringleb PA, Schell M, Schlemm E, Schönenberger S, Tennøe B, Ulfert C, Vališ K, Vítková E, Vollherbst DF, Wick W, Bendszus M, TENSION Investigators.

2024-07-2632 citations

10.1016/s1474-4422(24)00278-3

Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial.

Bendszus M, Fiehler J, Subtil F, Bonekamp S, Aamodt AH, Fuentes B, Gizewski ER, Hill MD, Krajina A, Pierot L, Simonsen CZ, Zeleňák 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, Kurča E, Mikkelsen R, Möhlenbruch M, Müller-Hülsbeck S, Münnich N, Pagano P, Papanagiotou P, Petzold GC, Pham M, Puetz V, Raupach J, Reimann G, Ringleb PA, Schell M, Schlemm E, Schönenberger S, Tennøe B, Ulfert C, Vališ K, Vítková E, Vollherbst DF, Wick W, Thomalla G, TENSION Investigators.

2023-10-11279 citations

10.1016/s0140-6736(23)02032-9

Mechanical Thrombectomy in Ischemic Stroke Patients With Alberta Stroke Program Early Computed Tomography Score 0–5

Johannes Kaesmacher, Panagiotis Chaloulos-Iakovidis, Leonidas D Panos, Pasquale Mordasini, Patrik Michel et al. (18 authors)

Stroke2019-03-04130 citations

10.1161/strokeaha.118.023465

A randomized controlled trial to test efficacy and safety of thrombectomy in stroke with extended lesion and extended time window

Martin Bendszus, Susanne Bonekamp, Eivind Berge, Florent Boutitie, Patrick A. Brouwer et al. (13 authors)

International Journal of Stroke2018-08-2984 citations

10.1177/1747493018798558

Interventions

DEVICEThrombectomy

Mechanical thrombectomy with state of the art thrombectomy devices (i.e. stent-retrievers, aspiration catheters). Devices will be used per instructions for use (IFU).

OTHERBest 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Intervention model description

prospective, open label, blinded endpoint (PROBE), European, two-arm, randomized, controlled, post-market study

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Clinical outcome-modified Rankin Scale at 90 days	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

Measure	Time frame	Description
Moderate Outcome - modified Rankin Scale≤3 at 90 days	90 days	Moderate neurological outcome with 90-day mRS≤3
Infarct volume 24 hours post procedure	18-36 hours	Infarct volume at 24 hours on post-procedure imaging
Infarct growth	18-36 hours	Difference of infarct volume from infarct volume as predicted by pre-treatment imaging
Functional neurological outcome at 12 months - modified Rankin Scale	12 month	Functional neurological outcome at 12 months (±14 days) after stroke (simplified modified Rankin Scale questionnaire, smRSq)
Quality of life - PROMIS-10	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.
Quality of life - EQ-5D	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).
Post-stroke depression - Patient Health Questionnaire-4	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)
Independence - modified Rankin Scale≤2 at 90 days	90 days	Independent neurological outcomes with 90-day mRS≤2
modified Rankin Scale between 4-6	12 month	Death or dependency
Frequencies of Adverse Events (AE) in both treatment arms within the first 7 days	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
Serious AEs	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).
Space-occupying infarction	18-36 hours	Malignant brain edema after treatment
New ischemic stroke	12 month	New AIS after treatment
Symptomatic intracranial hemorrhage (sICH) at 24 (18-36) hours (CT or MRI)	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
Cost Utility Assessment	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
Parenchymal hemorrhage type 2	90 days	blood clots in \>30% of the infarcted area with a substantial space-occupying effect.

Countries

Austria, Canada, Czechia, Denmark, France, Germany, Norway, Slovakia, Spain, Switzerland

Outcome results

None listed