Clinical trial NCT05029414: EnDovascular Therapy Plus Best Medical Treatment (BMT) Versus BMT Alone for MedIum VeSsel Occlusion sTroke
Official title: EnDovascular Therapy Plus Best Medical Treatment (BMT) Versus BMT Alone for MedIum VeSsel Occlusion sTroke - a prAgmatic, International, Multicentre, Randomized triaL (DISTAL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Acute Ischemic Stroke
Keywords: Stroke
Medium Vessel Occlusion
Endovascular Therapy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Swiss National Fund for Scientific Research
name: Stryker Neurovascular
name: Penumbra Inc.
name: Medtronic
name: Phenox GmbH
name: Rapid Medical
name: Gottfried und Julia Bangerter- Rhyner-Stiftung, Basel
First posted: 2021-08-31
Enrollment: 543
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic, parallel group, randomized, open label, superiority trial with blinded endpoint assessment
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Degree of dependency and disability in everyday life (measured with the mRS)
timeFrame: at 90 days (± 14 days) after randomisation
Secondary outcomes:
measure: Change in National Institutes of Health Stroke Scale (NIHSS)
timeFrame: 24 hours post-randomization (+/- 6 hours)
measure: Assessment of Cognitive function using the validated Montreal cognitive assessment (MoCA)
timeFrame: at 90 days (± 14 days) after randomisation
measure: Change in Quality of life as assessed by the EuroQol-5D
timeFrame: at 90 ± 14 days and at 1 year after randomisation
measure: Degree of dependency and disability in everyday life (measured with the mRS)
timeFrame: at one year (± 30 days) after randomisation
measure: Patient residential status
timeFrame: at one year (± 30 days) after randomisation
measure: Change in percentage of penumbral tissue saved (Imaging Data Evaluation)
timeFrame: at baseline and post-interventional at 24 hours (± 6 hours) post-randomisation
measure: Radiologic occurrence of intracranial haemorrhages
timeFrame: within 24 hours (± 6 hours) post randomisation
Other outcomes:
measure: Change in All-cause mortality (Safety Outcome)
timeFrame: at days 7-10 or discharge if earlier, 90 day ± 14 days; and one year ± 30 days after randomisation.
measure: Change in Serious Adverse Events (SAEs)
timeFrame: at 24 h ± 6h, days 7-10 or discharge if earlier and at 90 ± 14 days after randomisation
measure: Change in symptomatic intracranial haemorrhage
timeFrame: at 24 ± 6 hours post randomisation
Locations:
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge
city: Charleroi
country: Belgium
facility: Hôpital Civil Marie Curie Charleroi
city: Gent
country: Belgium
facility: UZ Universiteit Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Liege
country: Belgium
facility: Clinique CHC MontLégia
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Aachen
country: Germany
facility: Uniklinik RHTW Aachen
city: Berlin
country: Germany
facility: Charité-Universitätsmedizin Berlin
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte
city: Dresden
country: Germany
facility: Uniklinikum Dresden
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
city: Göttingen
country: Germany
facility: University Medical Center Göttingen
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona, Hamburg
city: Hamburg
country: Germany
facility: University Hospital Hamburg Eppendorf
city: Mannheim
country: Germany
facility: University Medical Center Mannheim
city: München
country: Germany
facility: Universitätsklinikum der Technischen Universität München
city: Münster
country: Germany
facility: University Hospital Münster
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg
city: Recklinghausen
country: Germany
facility: Klinikum VEST GmbH
city: Stuttgart
country: Germany
facility: Klinikum der Landeshauptstadt Stuttgart gKAöR
city: Jerusalem
country: Israel
facility: Hadassah-Hebrew University Medical Center
city: Bologna
country: Italy
facility: Maggiore Hospital
city: Firenze
country: Italy
facility: Careggi University Hospital,
city: Napoli
country: Italy
facility: Antonio Cardarelli Hospital
city: Torino
country: Italy
facility: San Giovanni Bosco Hospital
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital Arnhem
city: Den Haag
country: Netherlands
facility: Haaglanden Medical Center
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center Nijmegen
city: Rotterdam
country: Netherlands
facility: Erasmus MC University Medical Center Rotterdam
city: Lisbon
country: Portugal
facility: Lisbon Central University Hospital
city: Barcelona
country: Spain
facility: Hospital Clinico Barcelona
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: University Hospital Germans Trias i Pujol
city: Girona
country: Spain
facility: University Hospital Doctor Josep Trueta, Girona
city: Madrid
country: Spain
facility: University Hospital Clínico San Carlos, Madrid
city: Murcia
country: Spain
facility: University Hospital Virgen de la Arrixaca, Murcia
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario de Valladolid
city: Lund
country: Sweden
facility: Skane University Hospital
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau, Department of Interventional and Diagnostical Neuroradiology
city: Basel
country: Switzerland
facility: Department of Interventional and Diagnostical Neuroradiology, Clinic of Radiology and Nuclear Medicine, University Hospital Basel
city: Basel
country: Switzerland
facility: Department of Neurology, University Hospital Basel
city: Bern
country: Switzerland
facility: Inselspital Bern, University Clinic for Neuroradiology
city: Genf
country: Switzerland
facility: Geneva University Hospitals, Interventional Neuroradiology Unit
city: Lausanne
country: Switzerland
facility: Centre hospitalier universitaire vaudois, CHUV
city: Lugano
country: Switzerland
facility: Neurocentro (EOC) della Svizzera Italiana Stroke Center, Servizio di Neurologia, Ospedale Civico
city: Luzern
country: Switzerland
facility: Kantonsspital Luzern
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St Gallen
city: Zürich
country: Switzerland
facility: University Hospital Zurich, Departement of Neuroradiology
city: London
country: United Kingdom
facility: Barts NHS Health Trust
Study officials:
affiliation: Department of Interventional and Diagnostical Neuroradiology, University Hospital Basel
name: Marios-Nikos Psychogios, Prof.Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurology, Inselspital, Bern University Hospital
name: Urs Fischer, Prof.Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.