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

Not Applicable

Terminated

• Conditions: Apoplexy; Brain; Cerebral Stroke; Cerebrovascular Stroke; Stroke, Acute
• Interventions: Device: Thrombectomy; Other: Best medical care

• Registration Number: NCT03094715
• Lead Sponsor: 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 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.

Study Timeline

• Study First Submitted: 2017-03-16
• Study First Submitted QC: 2017-03-22
• Study First Posted: 2017-03-29
• Study Start: 2018-06-20
• Primary Completion: 2023-05-31
• Status Verified: 2023-11
• Study Completion: 2023-11-15
• Last Update Submitted: 2023-11-28
• Last Update Posted: 2023-12-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 253

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Thrombectomy	Thrombectomy	Endovascular thrombectomy and best medical care
Best medical care	Best medical care	Best medical treatment

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
New ischemic stroke	12 month	New AIS after treatment
Infarct volume 24 hours post procedure	18-36 hours	Infarct volume at 24 hours on post-procedure imaging
Independence - modified Rankin Scale≤2 at 90 days	90 days	Independent neurological outcomes with 90-day mRS≤2
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
Quality of life - PROMIS-10	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.
Moderate Outcome - modified Rankin Scale≤3 at 90 days	90 days	Moderate neurological outcome with 90-day mRS≤3
Post-stroke depression - Patient Health Questionnaire-4	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)
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)
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
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
Quality of life - EQ-5D	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).
Parenchymal hemorrhage type 2	90 days	blood clots in \>30% of the infarcted area with a substantial space-occupying effect.
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

Trial Locations

Locations (42)

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

University of Calgary; 🇨🇦 Calgary, Alberta, Canada

Department of Neurology, Reseach Institute of Neurointervention, Christian Doppler Clinic, Paracelsus Medical University Salzburg; 🇦🇹 Salzburg, Austria

Haukeland University Hospital; 🇳🇴 Bergen, Norway

St. Anne's University Hospital Brno; 🇨🇿 Brno, Czechia

Faculty Hospital Hradec Kralove; 🇨🇿 Hradec Kralove,, Czechia

Dept. of Radiology, Masaryk hospital; 🇨🇿 Usti nad Labem, Czechia

Comprehensive stroke center,University Hospital Ostrava; 🇨🇿 Ostrava, Czechia

Aalborg University Hospital; 🇩🇰 Aalborg, Denmark

Homolka Hospital Prague; 🇨🇿 Prague, Czechia

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

CHU Gabriel Montpied, Clermont-Ferrand; 🇫🇷 Clermont-Ferrand, France

University Hospital Rigshospitalet; 🇩🇰 Copenhagen, Denmark

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

CHRU Hôpiteaux de Tours / Hôpital Bretonneau; 🇫🇷 Tours, France

Otto-von-Guericke-University Magdeburg; 🇩🇪 Magdeburg, Sachsen-Anhalt, Germany

CHU de Rennes/Centre Urgences-Réanimations; 🇫🇷 Rennes, France

Universitätsklinikum KK Bochum-Langendreer Institut für Diagnostische und Interventionelle Radiologie, Neuroradiologie und Nuklearmedizin; 🇩🇪 Bochum, Germany

Universitätsinstitut für Diagnostische Radiologie, Neuroradiologie und Nuklearmedizin Johannes Wesling Klinikum Minden; 🇩🇪 Minden, Nordrhein-Westfalen, Germany

Gesundheit Nord gGmbH Klinikverbund Bremen; 🇩🇪 Bremen, Germany

Universitätsklinikum Bonn; 🇩🇪 Bonn, Germany

Alfried Krupp Krankenhaus Rüttenscheid; 🇩🇪 Essen, Germany

Klinik für Radiologie und Neuroradiologie am Klinikum Mitte; 🇩🇪 Dortmund, Germany

Universitätsklinikum Carl Gustav Carus Dresden; 🇩🇪 Dresden, Germany

Diakonissenkrankenhaus Flensburg; 🇩🇪 Flensburg, Germany

Klinikum der Universität München; 🇩🇪 München, Germany

Universitätsklinikum Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Neuroradiologie Universitätsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Universitätsklinikum Leipzig AöR; 🇩🇪 Leipzig, Germany

UKSH Universitätsklinikum Schleswig-Holstein Campus Lübeck; 🇩🇪 Lübeck, Germany

Technische Universität München / Klinikum rechts der Isar; 🇩🇪 München, Germany

Universitätsklinikum Würzburg; 🇩🇪 Würzburg, Germany

Oslo University Hospital; 🇳🇴 Oslo, Norway

The Arctic University of Norway; 🇳🇴 Tromsø, Norway

Comenius University's Jessenius Faculty of Medicine and University Hospital; 🇸🇰 Martin, Slovakia

Faculty Hospital Trnava; 🇸🇰 Trnava, Slovakia

University Hospital Basel; 🇨🇭 Basel, Switzerland

La Paz University Hospital; 🇪🇸 Madrid, Spain