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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Procedure: Endovascular Therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 543
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium
    • AZ Sint-Jan Brugge
  • Charleroi, Belgium
    • Hôpital Civil Marie Curie Charleroi
  • Gent, Belgium
    • UZ Universiteit Gent
  • Kortrijk, Belgium
    • AZ Groeninge
  • Leuven, Belgium
    • Universitair Ziekenhuis Leuven
  • Liege, Belgium
    • Clinique CHC MontLégia
• Finland
  • Helsinki, Finland
    • Helsinki University Hospital
  • Turku, Finland
    • Turku University Hospital
• Germany
  • Aachen, Germany
    • Uniklinik RHTW Aachen
  • Berlin, Germany
    • Charite-Universitatsmedizin Berlin
  • Bremen, Germany
    • Klinikum Bremen-Mitte
  • Dresden, Germany
    • Uniklinikum Dresden
  • Erfurt, Germany
    • HELIOS Klinikum Erfurt
  • Frankfurt, Germany
    • University Hospital Frankfurt
  • Göttingen, Germany
    • University Medical Center Göttingen
  • Hamburg, Germany
    • University Hospital Hamburg Eppendorf
  • Hamburg, Germany
    • Asklepios Klinik Altona, Hamburg
  • Mannheim, Germany
    • University Medical Center Mannheim
  • München, Germany
    • Universitätsklinikum der Technischen Universität München
  • Münster, Germany
    • University Hospital Münster
  • Nürnberg, Germany
    • Klinikum Nürnberg
  • Recklinghausen, Germany
    • Klinikum VEST GmbH
  • Stuttgart, Germany
    • Klinikum Der Landeshauptstadt Stuttgart gKAöR
• Israel
  • Jerusalem, Israel
    • Hadassah-Hebrew University Medical Center
• Italy
  • Bologna, Italy
    • Maggiore Hospital
  • Firenze, Italy
    • Careggi University Hospital,
  • Napoli, Italy
    • Antonio Cardarelli Hospital
  • Torino, Italy
    • San Giovanni Bosco Hospital
• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam University Medical Center
  • Arnhem, Netherlands
    • Rijnstate Hospital Arnhem
  • Den Haag, Netherlands
    • Haaglanden Medical Center
  • Groningen, Netherlands
    • University Medical Center Groningen
  • Leiden, Netherlands
    • Leiden University Medical Center
  • Maastricht, Netherlands
    • Maastricht University Medical Center
  • Nijmegen, Netherlands
    • Radboud University Medical Center Nijmegen
  • Rotterdam, Netherlands
    • Erasmus MC University Medical Center Rotterdam
• Portugal
  • Lisbon, Portugal
    • Lisbon Central University Hospital
• Spain
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Barcelona, Spain
    • Hospital Clinico Barcelona
  • Barcelona, Spain
    • University Hospital Germans Trias i Pujol
  • Girona, Spain
    • University Hospital Doctor Josep Trueta, Girona
  • Madrid, Spain
    • University Hospital Clínico San Carlos, Madrid
  • Murcia, Spain
    • University Hospital Virgen de la Arrixaca, Murcia
  • Valladolid, Spain
    • Hospital Clinico Universitario de Valladolid
• Sweden
  • Lund, Sweden
    • Skåne University Hospital
• Switzerland
  • Aarau, Switzerland, 5001
    • Kantonsspital Aarau, Department of Interventional and Diagnostical Neuroradiology
  • Basel, Switzerland, 4031
    • Department of Neurology, University Hospital Basel
  • Basel, Switzerland, 4031
    • Department of Interventional and Diagnostical Neuroradiology, Clinic of Radiology and Nuclear Medicine, University Hospital Basel
  • Bern, Switzerland, 3010
    • Inselspital Bern, University Clinic for Neuroradiology
  • Genf, Switzerland, 1211
    • Geneva University Hospitals, Interventional Neuroradiology Unit
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois, CHUV
  • Lugano, Switzerland, 6900
    • Neurocentro (EOC) della Svizzera Italiana Stroke Center, Servizio di Neurologia, Ospedale Civico
  • Luzern, Switzerland
    • Kantonsspital Luzern
  • Saint Gallen, Switzerland
    • Kantonsspital St Gallen
  • Zürich, Switzerland, 8091
    • University Hospital Zurich, Departement of Neuroradiology
• United Kingdom
  • London, United Kingdom
    • Barts NHS Health Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group: EVT + BMT; 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; 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.
No Intervention: Control group: BMT; 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?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in All-cause mortality (Safety Outcome)	Change in All-cause mortality	at days 7-10 or discharge if earlier, 90 day ± 14 days; and one year ± 30 days after randomisation.
Change in Serious Adverse Events (SAEs)	Change in Serious Adverse Events (SAEs)	at 24 h ± 6h, days 7-10 or discharge if earlier and at 90 ± 14 days after randomisation
Change in symptomatic intracranial haemorrhage	Change in symptomatic intracranial haemorrhage by radiologic categorization on the basis of the pre-randomisation imaging at day 0 (Non contrast computed tomography (NCCT)/Magnet Resonance Imaging (MRI), Computed tomography angiography (CTA)/Magnetic Resonance Angiography (MRA), Diffusion Weighted Imaging (DWI)/Perfusion Weighted Imaging (PWI) MRI, Compute tomography (CT) perfusion) and the post-interventional imaging at 24 ± 6 hours.	at 24 ± 6 hours post randomisation

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Stryker Neurovascular; Medtronic; Swiss National Fund for Scientific Research; Phenox GmbH; Penumbra Inc.; Rapid Medical; Gottfried und Julia Bangerter-Rhyner-Stiftung
• Investigators: Principal Investigator: Marios-Nikos Psychogios, Prof.Dr., Department of Interventional and Diagnostical Neuroradiology, University Hospital Basel; Principal Investigator: Urs Fischer, Prof.Dr., Neurology, Inselspital, Bern University Hospital

Publications and helpful links

General Publications

• Marios-Nikos P, Alex B, Jens F, Isabel F, Jan G, Mira K, Ronen L, Paolo M, Marc R, Jeffrey L S, Daniel S, Adriaan VE, Claus Z, Nikki R, Luzia B, Urs F. EnDovascular therapy plus best medical treatment (BMT) versus BMT alone for medIum distal veSsel occlusion sTroke (DISTAL): An international, multicentre, randomized-controlled, two-arm, assessor-blinded trial. Eur Stroke J. 2024 Dec;9(4):1083-1092. doi: 10.1177/23969873241250212. Epub 2024 May 3.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2021
• Primary Completion (Actual): October 10, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Stroke; Endovascular Therapy; Medium Vessel Occlusion
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke
• Other Study ID Numbers: 2021-01692; qu20Psychogios2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No