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

Stroke, Acute Clinical Trial

— Tension  

Official title:

Efficacy and Safety of Thrombectomy in Stroke With Extended Lesion and Extended Time Window: a Randomized, Controlled Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03094715
• Other study ID #: TENSION
• Status: Terminated
• Phase: N/A
• Start date: June 20, 2018
• Est. completion date: November 15, 2023

Study information

• Verified date: November 2023
• Source: University Hospital Heidelberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 253
• Est. completion date: November 15, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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:
• 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.

Locations

Country	Name	City	State
Austria	Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University Graz	Graz
Austria	Medical University Innsbruck	Innsbruck
Austria	Neuroradiology, Keppler University Hospital Linz	Linz
Austria	Department of Neurology, Reseach Institute of Neurointervention, Christian Doppler Clinic, Paracelsus Medical University Salzburg	Salzburg
Canada	University of Calgary	Calgary	Alberta
Czechia	St. Anne's University Hospital Brno	Brno
Czechia	Faculty Hospital Hradec Kralove	Hradec Kralove,
Czechia	Comprehensive stroke center,University Hospital Ostrava	Ostrava
Czechia	Homolka Hospital Prague	Prague
Czechia	Dept. of Radiology, Masaryk hospital	Usti nad Labem
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	University Hospital Rigshospitalet	Copenhagen
France	CHU Gabriel Montpied, Clermont-Ferrand	Clermont-Ferrand
France	Hôpiteaux Universitaires Paris-Sud, Hôpital Bicêtre	Le Kremlin-Bicêtre
France	Hôpital Pitié-Salpêtrière	Paris
France	Université Reims Champagne Ardenne/ Department of Neuroradiology, Hôpital Maison Blanche	Reims
France	CHU de Rennes/Centre Urgences-Réanimations	Rennes
France	CHRU Hôpiteaux de Tours / Hôpital Bretonneau	Tours
Germany	Universitätsklinikum KK Bochum-Langendreer Institut für Diagnostische und Interventionelle Radiologie, Neuroradiologie und Nuklearmedizin	Bochum
Germany	Universitätsklinikum Bonn	Bonn
Germany	Gesundheit Nord gGmbH Klinikverbund Bremen	Bremen
Germany	Klinik für Radiologie und Neuroradiologie am Klinikum Mitte	Dortmund
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Alfried Krupp Krankenhaus Rüttenscheid	Essen
Germany	Diakonissenkrankenhaus Flensburg	Flensburg
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Neuroradiologie Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Leipzig AöR	Leipzig
Germany	UKSH Universitätsklinikum Schleswig-Holstein Campus Lübeck	Lübeck
Germany	Otto-von-Guericke-University Magdeburg	Magdeburg	Sachsen-Anhalt
Germany	Universitätsinstitut für Diagnostische Radiologie, Neuroradiologie und Nuklearmedizin Johannes Wesling Klinikum Minden	Minden	Nordrhein-Westfalen
Germany	Klinikum der Universität München	München
Germany	Technische Universität München / Klinikum rechts der Isar	München
Germany	Universitätsklinikum Würzburg	Würzburg
Norway	Haukeland University Hospital	Bergen
Norway	Oslo University Hospital	Oslo
Norway	The Arctic University of Norway	Tromsø
Slovakia	Comenius University's Jessenius Faculty of Medicine and University Hospital	Martin
Slovakia	Faculty Hospital Trnava	Trnava
Spain	La Paz University Hospital	Madrid
Switzerland	University Hospital Basel	Basel

Sponsors (16)

Lead Sponsor

Collaborator

University Hospital Heidelberg

Aarhus University Hospital, Charles University, Czech Republic, CHU de Reims, Epidemiological and Clinical Research Information Network, Eppdata GmbH Hamburg, Germany, Europan Society for Minimally Invasive Neurological Therapy, Groupe Hospitalier Pitie-Salpetriere, Hospices Civils de Lyon, International Consortium for Health Outcome Measurement, Inc., Karolinska University Hospital, Medical University Innsbruck, Oslo University Hospital, STROKE ALLIANCE FOR EUROPE, Universitätsklinikum Hamburg-Eppendorf, University Hospital, Martin

Countries where clinical trial is conducted

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

References & Publications (3)

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. — View 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 — View 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 — View Citation

Outcome

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