Bridging Thrombolysis Versus Direct Mechanical Thrombectomy in Acute Ischemic Stroke

NCT03192332 | Completed DMC

• 1 other identifier: 2017-00974
• Study Type: interventional
• Target: 410
• Locations: 8 countries
• Sites: 48

Brief Summary

Intravenous thrombolysis with recombinant tissue-type plasminogen activator (IV t-PA) has been the only proven therapy for acute ischemic stroke (AIS) for almost 20 years. Whether IV t-PA prior to endovascular clot retrieval is beneficial for AIS patients with a proximal vessel occlusion in the anterior circulation has currently become a matter of debate and is a relevant unanswered question in clinical practice. The main objective is to determine whether subjects experiencing an AIS due to large intracranial vessel occlusion in the anterior circulation will have non-inferior functional outcome at 90 days when treated with direct mechanical thrombectomy (MT) compared to subjects treated with combined IV t-PA and MT. The secondary objectives are to study causes of mortality, dependency and quality of life in these AIS patients.

Conditions

Ischemic Stroke

Keywords

Intravenous thrombolysis; Endovascular treatment; Mechanical thrombectomy; Bridging thrombolysis; Acute ischemic stroke

Outcome Measures

Primary Outcomes (1)

• Score in modified Rankin Scale (mRS)

  90 days after randomization

Secondary Outcomes (8)

• Mortality

  90 days after randomization

• Modified Rankin Scale (mRS) shift analysis

  day 0 and 90 days after randomization

• National Institute of Health Score Scale (NIHSS)

  day 0 and day 1 after randomization

• Thrombolysis in Cerebral Infarction (TICI) scale

  day 0 and day 1 after randomization

• Serious adverse events

  day 0 until 90 days after randomization

Study Arms (2)

Direct mechanical thrombectomy

EXPERIMENTAL

Treatment with direct mechanical thrombectomy with a commercially available stent-retriever revascularization device of the Solitaire™ type.

Device: Stent-retriever thrombectomy with revascularization device of the Solitaire™ type

Combined intravenous thrombolysis and mechanical thrombectomy

ACTIVE COMPARATOR

Treatment with intravenous thrombolysis with recombinant tissue-type plasminogen activator (IV t-PA) followed by mechanical thrombectomy with a commercially available stent-retriever revascularization device of the Solitaire™ type.

Device: Stent-retriever thrombectomy with revascularization device of the Solitaire™ type; Drug: Intravenous thrombolysis with recombinant tissue-type plasminogen activator (IV t-PA)

Interventions

Stent-retriever thrombectomy with revascularization device of the Solitaire™ type DEVICE

Mechanical thrombectomy with a stent-retriever revascularization device

Combined intravenous thrombolysis and mechanical thrombectomy; Direct mechanical thrombectomy

Intravenous thrombolysis with recombinant tissue-type plasminogen activator (IV t-PA) DRUG

Bridging thrombolysis (IV t-PA plus mechanical thrombectomy) according to current European and North American stroke guidelines.

Combined intravenous thrombolysis and mechanical thrombectomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent as documented by signature
• Age ≥ 18
• Clinical signs consistent with an acute ischemic stroke
• Neurological deficit with a NIHSS of ≥ 5 and \< 30 (deficits judged to be clearly disabling at presentation)
• Patient is eligible for intravenous thrombolysis
• Patient is eligible for endovascular treatment
• Randomization no later than 4 hours 15 minutes after stroke symptom onset and initiation of IV t-PA must be started within 4 hours 30 minutes of stroke symptoms onset (onset time is measured from the time when the subject was last seen well)
• Occlusion (TICI 0-1) of the intracranial internal carotid artery (ICA), the M1 segment of the middle cerebral artery (MCA), or both confirmed by CT or MR angiography, accessible for MT
• Core-infarct volume of Alberta Stroke Program Early CT Score (ASPECTS) greater than or equal to 4 (≥ 4) based on baseline CT or MR imaging (MRI) (a region has to have diffusion abnormality in 20% or more of its volume to be considered MR-ASPECTS positive)

You may not qualify if:

• Acute intracranial hemorrhage
• Any contraindication for IV t-PA
• Pre-treatment with IV t-PA
• In-hospital stroke
• Pregnancy or lactating women. A negative pregnancy test before randomization is required for all women with child-bearing potential.
• Known (serious) sensitivity to radiographic contrast agents, nickel, titanium metals, or their alloys
• Known current participation in a clinical trial (investigational drug or medical device)
• Renal insufficiency as defined by a serum creatinine \> 2.0 mg/dl (or 176.8 µmol/l) or glomerular filtration rate (GFR) \< 30 mL/min or requirement for hemodialysis or peritoneal dialysis
• Severe comorbid condition with life expectancy less than 90 days at baseline
• Known advanced dementia or significant pre-stroke disability (mRS score of ≥2)
• Foreseeable difficulties in follow-up due to geographic reasons (e.g. patients living abroad)
• Comorbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments.
• Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than four alcoholic drinks per day).
• Known history of arterial tortuosity, pre-existing stent, other arterial disease and/or known disease at the femoral access site that would prevent the device from reaching the target vessel and/or preclude safe recovery after MT
• Radiological confirmed evidence of mass effect or intracranial tumor (except small meningioma)

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Medtronic: collaborator

Study Sites (48)

Keppler Universitätsklinikum

Linz, Upper Austria, 4020, Austria

Location

Medical University of Innsbruck

Innsbruck, 6020, Austria

Location

University of Calgary, Alberta Health Services

Calgary, Canada

Location

Mc Gill University

Montreal, Canada

Location

Royal University Hospital, University of Saskatchewan

Saskatoon, Canada

Location

Toronto Western Hospital

Toronto, Canada

Location

Helsinki University Hospital

Helsinki, 00290, Finland

Location

Hôpital Cavale Blanche CHU Brest

Brest, Finistère, 29200, France

Location

CHU de Reims

Reims, Marne, 51100, France

Location

CHU de Clermont-Ferrand

Clermont-Ferrand, Puy-de-Dôme, 63000, France

Location

CHU de Bordeaux

Bordeaux, 33404, France

Location

CHU de Caen Normandie

Caen, 14033, France

Location

CHU de Lille

Lille, 59037, France

Location

CHU de Limoges

Limoges, 87042, France

Location

Hospices Civils de Lyon

Lyon, 69002, France

Location

CHU de Montpellier

Montpellier, France

Location

CHRU Nancy

Nancy, 54035, France

Location

CHU de Nantes

Nantes, 44093, France

Location

Hôpital Bicêtre

Paris, 75010, France

Location

GHU Paris Psychiatrie et Neurosciences, Sainte Anne

Paris, 75014, France

Location

Fondation Ophtalmologique A. de Rothschild

Paris, 75019, France

Location

CHU Rouen Normandie

Rouen, 76031, France

Location

CHRU Strasbourg

Strasbourg, 67091, France

Location

CHU de Toulouse

Toulouse, 31059, France

Location

CHU Tours

Tours, 37044, France

Location

Hôpital Foch

Suresnes, Île-de-France Region, 92150, France

Location

Universitätsmedizin Mannheim, Universität Heidelber

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Klinikum Osnabrück GmbH

Osnabrück, Lower Saxony, 49076, Germany

Location

Universitätsklinikum RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Universitätsklinikum Schleswig-Holstein, Campus Kiel

Kiel, Schleswig-Holstein, 24105, Germany

Location

Universitätsklinikum Knappschaftskrankenhaus GmbH Bochum

Bochum, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, 60528, Germany

Location

Universitätsmedizin Göttingen

Göttingen, 37075, Germany

Location

Medizinische Fakultät der Otto-von-Guericke-Universität Magdeburg

Magdeburg, Germany

Location

Klinikum rechts der Isar der Technischen Universität München

München, Germany

Location

Klinikum Vest GmbH

Recklinghausen, Germany

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitari Germans Trias i Pujol

Barcelona, 08916, Spain

Location

Dept. of Neurology, Kantonsspital Aarau

Aarau, Canton of Aargau, 5001, Switzerland

Location

Dept. of Neurology, Centre hospitalier universitaire vaudois (CHUV)

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Dept. of Neurology, Ospedale Civo of Lugano

Lugano, Canton Ticino, 6900, Switzerland

Location

Dept. of Neurology, Bern University Hospital

Bern, 3010, Switzerland

Location

Hôpitaux Universitaires de Genève - HUG

Geneva, 1211, Switzerland

Location

Kantonsspital St.Gallen

Sankt Gallen, 9007, Switzerland

Location

Dept. of Neuroradiology, UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

Belfast City Hospital

Belfast, United Kingdom

Location

St George's University Hospitals NHS Foundation Trust

London, United Kingdom

Location

Salford Royal

Salford, United Kingdom

Location

Related Publications (5)

• Fladt J, Kaesmacher J, Meinel TR, Butikofer L, Strbian D, Eker OF, Albucher JF, Desal H, Marnat G, Papagiannaki C, Richard S, Requena M, Lapergue B, Pagano P, Ernst M, Wiesmann M, Boulanger M, Liebeskind DS, Gralla J, Fischer U. MRI vs CT for Baseline Imaging Evaluation in Acute Large Artery Ischemic Stroke: A Subanalysis of the SWIFT-DIRECT Trial. Neurology. 2024 Jan 23;102(2):e207922. doi: 10.1212/WNL.0000000000207922. Epub 2023 Dec 14.

  PMID: 38165324 DERIVED

• Mujanovic A, Eker O, Marnat G, Strbian D, Ijas P, Preterre C, Triquenot A, Albucher JF, Gauberti M, Weisenburger-Lile D, Ernst M, Nikoubashman O, Mpotsaris A, Gory B, Tuan Hua V, Ribo M, Liebeskind DS, Dobrocky T, Meinel TR, Buetikofer L, Gralla J, Fischer U, Kaesmacher J; SWIFT DIRECT investigators. Association of intravenous thrombolysis and pre-interventional reperfusion: a post hoc analysis of the SWIFT DIRECT trial. J Neurointerv Surg. 2023 Nov;15(e2):e232-e239. doi: 10.1136/jnis-2022-019585. Epub 2022 Nov 17.

  PMID: 36396433 DERIVED

• Meinel TR, Kaesmacher J, Buetikofer L, Strbian D, Eker OF, Cognard C, Mordasini P, Deppeler S, Mendes Pereira V, Albucher JF, Darcourt J, Bourcier R, Guillon B, Papagiannaki C, Costentin G, Sibolt G, Raty S, Gory B, Richard S, Liman J, Ernst M, Boulanger M, Barbier C, Mechtouff L, Zhang L, Marnat G, Sibon I, Nikoubashman O, Reich A, Consoli A, Weisenburger D, Requena M, Garcia-Tornel A, Saleme S, Moulin S, Pagano P, Saliou G, Carrera E, Janot K, Boix M, Pop R, Della Schiava L, Luft A, Piotin M, Gentric JC, Pikula A, Pfeilschifter W, Arnold M, Siddiqui A, Froehler MT, Furlan AJ, Chapot R, Wiesmann M, Machi P, Diener HC, Kulcsar Z, Bonati L, Bassetti C, Escalard S, Liebeskind D, Saver JL, Fischer U, Gralla J; SWIFT-DIRECT investigators. Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial. J Neurointerv Surg. 2023 Sep;15(e1):e102-e110. doi: 10.1136/jnis-2022-019207. Epub 2022 Jul 28.

  PMID: 35902234 DERIVED

• Fischer U, Kaesmacher J, Strbian D, Eker O, Cognard C, Plattner PS, Butikofer L, Mordasini P, Deppeler S, Pereira VM, Albucher JF, Darcourt J, Bourcier R, Benoit G, Papagiannaki C, Ozkul-Wermester O, Sibolt G, Tiainen M, Gory B, Richard S, Liman J, Ernst MS, Boulanger M, Barbier C, Mechtouff L, Zhang L, Marnat G, Sibon I, Nikoubashman O, Reich A, Consoli A, Lapergue B, Ribo M, Tomasello A, Saleme S, Macian F, Moulin S, Pagano P, Saliou G, Carrera E, Janot K, Hernandez-Perez M, Pop R, Schiava LD, Luft AR, Piotin M, Gentric JC, Pikula A, Pfeilschifter W, Arnold M, Siddiqui AH, Froehler MT, Furlan AJ, Chapot R, Wiesmann M, Machi P, Diener HC, Kulcsar Z, Bonati LH, Bassetti CL, Mazighi M, Liebeskind DS, Saver JL, Gralla J; SWIFT DIRECT Collaborators. Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial. Lancet. 2022 Jul 9;400(10346):104-115. doi: 10.1016/S0140-6736(22)00537-2.

  PMID: 35810756 DERIVED

• Fischer U, Kaesmacher J, S Plattner P, Butikofer L, Mordasini P, Deppeler S, Cognard C, Pereira VM, Siddiqui AH, Froehler MT, Furlan AJ, Chapot R, Strbian D, Wiesmann M, Bressan J, Lerch S, Liebeskind DS, Saver JL, Gralla J; SWIFT DIRECT study investigators. SWIFT DIRECT: Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA Versus DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke: Methodology of a randomized, controlled, multicentre study. Int J Stroke. 2022 Jul;17(6):698-705. doi: 10.1177/17474930211048768. Epub 2021 Oct 14.

  PMID: 34569878 DERIVED

Related Links

• Trial Website

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Urs Fischer, Prof. Dr.

  Dept. of Neurology, Inselspital Bern

  PRINCIPAL INVESTIGATOR

• Jan Gralla, Prof. Dr.

  Dept. of Neuroradiology, Inselspital Bern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Assessment of the primary outcome will be performed by an independent and blinded person.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, randomized, open label, blinded endpoint (PROBE)

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: June 20, 2017
• Study Start: November 29, 2017
• Primary Completion: May 14, 2021
• Study Completion: August 11, 2021
• Last Updated: November 14, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1); DE (10); GB (3); AU (2); CH (7); FR (19); ES (2); CA (4)