EnDovascular Therapy Plus Best Medical Treatment (BMT) Versus BMT Alone for MedIum VeSsel Occlusion sTroke

Study Overview
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Brief Summary
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Acute ischemic stroke (AIS) is one of the main causes of disability and loss of quality adjusted life years. This study is to analyze whether endovascular therapy (EVT) in addition to best medical treatment (BMT) reduces the degree of disability and dependency in daily activities after a Medium Vessel Occlusion (MeVO) stroke compared to BMT alone.

Detailed Description
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Acute ischemic stroke (AIS) is one of the main causes of death and disability and thereby the third leading cause of loss of quality adjusted life years. For patients with an AIS due to an occlusion of the large vessels of the anterior circulation, endovascular therapy (EVT) has become a treatment standard. 20-40% of all AIS patients have occlusions of smaller vessels and present with a more distal isolated Medium Vessel Occlusion (MeVO). The primary objective of this randomized trial is to determine whether patients experiencing an AIS due to an isolated medium vessel occlusion have superior functional outcome (measured with the Modified Rankin Scale mRS at 90 days) when treated with EVT plus best medical treatment (BMT) compared to patients treated with BMT alone. In this trial, all commercially available, CE-certified revascularisation devices (i.e. stent-retriever, aspiration catheters and balloon guide catheters) can be used for EVT. All established techniques for the endovascular treatment of AIS patients are permitted and all decisions regarding treatment technique and choice of devices and/or medications are made solely by the treating physician.

Official Title
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EnDovascular Therapy Plus Best Medical Treatment (BMT) Versus BMT Alone for MedIum VeSsel Occlusion sTroke - a prAgmatic, International, Multicentre, Randomized triaL (DISTAL)

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Procedure: Endovascular Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute ischemic stroke Treatment (arterial puncture) can be initiated 2.1. Within 6 hours of last seen well (LSW) OR 2.2. Within 6 to 24 hours of LSW AND CT Criteria: Evidence of a hypoperfusion-hypodensity mismatch (Absence of hypodensity on the noncontrast CT within ≥ 90% of the area of the hypoperfused lesion on perfusion CT) MRI Criteria: Evidence of a diffusion-hyperintensity mismatch (Absence of hyperintensity on fluid-attenuated inversion recovery (FLAIR) imaging within ≥ 90% of the area of the diffusion weighted imaging(DWI) lesion) Isolated medium vessel occlusion (i.e. an occlusion of the co-/non-dominant M2, the M3/M4 segment of theMCA, the A1/A2/A3 segment of the ACA or the P1/P2/P3 segment of the PCA) confirmed by CT or MRIAngiography National Institute of Health Stroke Scale (NIHSS) Score of ≥ 4 points or symptoms deemed clearly disabling by treating physician (i.e. aphasia, hemianopia, etc.) Informed Consent as documented by signature or fulfilling the criteria for emergency consent/ deferral consent Agreement of treating physician to perform endovascular procedure Exclusion Criteria: Acute intracranial haemorrhage Patient bedridden or presenting from a nursing home In-Hospital Stroke Known (serious) sensitivity to radiographic contrast agents, nickel, titanium metals or their alloys Foreseeable difficulties in follow-up due to geographic reasons (e.g. patients living abroad) Pregnancy or lactating women. A negative pregnancy test before randomisation is required for all women with child-bearing potential. Known history of arterial tortuosity, pre-existing stent, other arterial disease and/or known disease at the arterial access site that would prevent the device from reaching the target vessel and/or preclude safe recovery after EVT Severe comorbidities, which will likely prevent improvement or follow-up Radiological confirmed evidence of mass effect or intracranial tumour (except small meningioma) Radiological confirmed evidence of cerebral vasculitis Evidence of vessel recanalization prior to randomisation Participation in another interventional trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pragmatic, parallel group, randomized, open label, superiority trial with blinded endpoint assessment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group: EVT + BMT<br>Patients randomized to the EVT arm will undergo endovascular therapy (EVT) in addition to best medical treatment (BMT). All decisions regarding EVT device and EVT technique will be made by the treating physician. | Procedure: Endovascular Therapy<br>* Endovascular treatment of stroke is the non-surgical treatment for the sudden loss of brain function due to blood clots. The blood clot is removed from the blood via devices (i.e. stent-retriever, aspiration catheters and balloon guide) to achieve revascularization.<br>|
| No Intervention: Control group: BMT<br>Patients randomized to the control arm will NOT undergo EVT but will get best medical treatment (BMT) including intravenous thrombolysis (IVT) or antiplatelet therapy if indicated under current international guidelines and according to routine clinical practice. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of dependency and disability in everyday life (measured with the mRS) | The primary outcome is the degree of dependency and disability in everyday life (measured with the mRS) at 90 days. The mRS is the standard tool to assess neurological outcome in trials with acute severe brain disease. The scale runs from 0-6, running from perfect health without symptoms (= 0) to death (= 6). | at 90 days (± 14 days) after randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in National Institutes of Health Stroke Scale (NIHSS) | The scale is made up of 11 different elements that evaluate specific ability. The score for each ability is a number between 0 and 4, 0 being normal functioning and 4 being completely impaired. The patient's NIHSS score is calculated by adding the number for each element of the scale; 42 is the highest score possible. In the NIHSS, the higher the score, the more impaired a stroke patient is. | 24 hours post-randomization (+/- 6 hours) | 
| Assessment of Cognitive function using the validated Montreal cognitive assessment (MoCA) | MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal. | at 90 days (± 14 days) after randomisation | 
| Change in Quality of life as assessed by the EuroQol-5D | The EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. the descriptive system produces a 5-digit health status profile that represents that person's level of reported problems on the five EQ-5D health dimensions | at 90 ± 14 days and at 1 year after randomisation | 
| Degree of dependency and disability in everyday life (measured with the mRS) | Degree of dependency and disability in everyday life (measured with the mRS). The scale runs from 0-6, running from perfect health without symptoms (= 0) to death (= 6). | at one year (± 30 days) after randomisation | 
| Patient residential status | Patient residential status will be obtained through a telephone call to the patient or if not available his next of kin/caregiver one year (± 30 days) after randomisation | at one year (± 30 days) after randomisation | 
| Change in percentage of penumbral tissue saved (Imaging Data Evaluation) | Percentage of penumbral tissue saved (Imaging Data Evaluation): It is defined as the proportion of tissue at risk (defined as the mismatch volume derived from with RAPID Compute tomography perfusion (CTP) (IschemaView Inc.) at baseline that did not progress to infarction at 24h (derived from Magnet Resonance Imaging (MRI) (FLAIR and Diffusion Weighted Imaging (DWI)) or NCCT imaging. | at baseline and post-interventional at 24 hours (± 6 hours) post-randomisation | 
| Radiologic occurrence of intracranial haemorrhages | Radiologic occurrence of intracranial haemorrhages graded according to the modified Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) definition | within 24 hours (± 6 hours) post randomisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Medium Vessel Occlusion, Endovascular Therapy