Bridging Thrombolysis Versus Direct Mechanical Thrombectomy in Acute Ischemic Stroke

NCT ID: NCT03192332

Last Updated: 2024-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 410 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-29
• Study Completion Date: 2021-08-11

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.

Detailed Description

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. Since December 2014 a new era in acute stroke treatment has begun: randomized controlled studies have consistently shown that endovascular clot retrieval in addition to best medical treatment (± IV t-PA) improves outcome in acute anterior circulation stroke patients with proximal vessel occlusion compared to best medical treatment alone. Whether pre-treatment with IV t-PA prior to endovascular clot retrieval is beneficial has now become a matter of debate. A pooled analysis of 5 RCTs (MR CLEAN, SWIFT-PRIME, EXTEND IA, ESCAPE and REVASCAT) suggested that the treatment effect size of MT does not differ between patients receiving intravenous thrombolysis (IVT) and those treated with MT alone (p interaction: 0.4311). Besides post-hoc RCT analyses, there are a myriad of observational studies reporting on rates of successful reperfusion and functional outcome stratified according to IV t-PA pretreatment status. There is evidence that reperfusion rates after IV t-PA in patients with occlusions of the internal carotid artery and the main stem of the middle cerebral artery are low, but may reach more than 80% after mechanical thrombectomy (MT). Therefore the most important factor for vessel recanalization, which is linked with favorable outcome, is MT.

No randomized controlled trial has ever assessed whether direct MT in patients with AIS is equally effective as MT in combination with IV t-PA (bridging thrombolysis). In a patient-level pooled analysis of five randomized controlled studies (HERMES collaboration) similar rates of functional independence and mortality at 90 days were observed between patients who received IV t-PA+MT and those who received direct MT. However, patients in the direct MT group had contraindications for IV t-PA. Two larger studies based on registries compared the outcome of patients after bridging thrombolysis with direct MT in patients eligible for IV t-PA. In both studies, the outcome of patients after bridging thrombolysis and direct MT was similar. For these reasons the investigators hypothesize that immediate and direct MT is not inferior and might even be superior to bridging thrombolysis in patients directly referred to a stroke center with rapid access to endovascular procedures.

In this trial all commercially available stent-retriever revascularization devices manufactured by Medtronic (e.g. Solitaire™) will be used as tool for direct MT. The investigators aim to provide conclusive information on the efficacy and safety of direct MT, in comparison with bridging thrombolysis.

If direct MT in patients with AIS would not be inferior to bridging thrombolysis, the organization of acute stroke management would change essentially. Direct MT would then be the therapy of choice in stroke centers with endovascular facilities. Furthermore, this trial could have an impact on healthcare guidelines and costs. However, this trial does not address the question, whether patients arriving in stroke units with no endovascular facilities should be pre-treated with IV t-PA or whether they should directly be referred to stroke centers with endovascular facilities.

Conditions

Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Direct mechanical thrombectomy

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

Group Type: EXPERIMENTAL

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

Intervention Type: DEVICE

Mechanical thrombectomy with a stent-retriever revascularization device

Combined intravenous thrombolysis and mechanical thrombectomy

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.

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: DEVICE

Mechanical thrombectomy with a stent-retriever revascularization device

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

Intervention Type: DRUG

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

Interventions

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

Mechanical thrombectomy with a stent-retriever revascularization device

Intervention Type: DEVICE

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

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Informed consent as documented by signature

2. Age ≥ 18

3. Clinical signs consistent with an acute ischemic stroke

4. Neurological deficit with a NIHSS of ≥ 5 and < 30 (deficits judged to be clearly disabling at presentation)

5. Patient is eligible for intravenous thrombolysis

6. Patient is eligible for endovascular treatment

7. 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)

8. 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

9. 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)

Exclusion Criteria

1. Acute intracranial hemorrhage

2. Any contraindication for IV t-PA

3. Pre-treatment with IV t-PA

4. In-hospital stroke

5. Pregnancy or lactating women. A negative pregnancy test before randomization is required for all women with child-bearing potential.

6. Known (serious) sensitivity to radiographic contrast agents, nickel, titanium metals, or their alloys

7. Known current participation in a clinical trial (investigational drug or medical device)

8. 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

9. Severe comorbid condition with life expectancy less than 90 days at baseline

10. Known advanced dementia or significant pre-stroke disability (mRS score of ≥2)

11. Foreseeable difficulties in follow-up due to geographic reasons (e.g. patients living abroad)

12. Comorbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments.

13. 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).

14. 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

15. Radiological confirmed evidence of mass effect or intracranial tumor (except small meningioma)

16. Radiological confirmed evidence of cerebral vasculitis

17. CTA or MRA evidence of carotid artery dissection

18. Evidence of additional distal intracranial vessel occlusion in another territory (i.e. A2 segment of anterior cerebral artery or M3, M4 segment of MCA) on initial NCCT/MRI or CTA/MRA

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medtronic

INDUSTRY

Sponsor Role: collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Urs Fischer, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Dept. of Neurology, Inselspital Bern

Jan Gralla, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Dept. of Neuroradiology, Inselspital Bern

Locations

Keppler Universitätsklinikum

Linz, Upper Austria, Austria

Medical University of Innsbruck

Innsbruck, , Austria

University of Calgary, Alberta Health Services

Calgary, , Canada

Mc Gill University

Montreal, , Canada

Royal University Hospital, University of Saskatchewan

Saskatoon, , Canada

Toronto Western Hospital

Toronto, , Canada

Helsinki University Hospital

Helsinki, , Finland

Hôpital Cavale Blanche CHU Brest

Brest, Finistère, France

CHU de Reims

Reims, Marne, France

CHU de Clermont-Ferrand

Clermont-Ferrand, Puy-de-Dôme, France

CHU de Bordeaux

Bordeaux, , France

CHU de Caen Normandie

Caen, , France

CHU de Lille

Lille, , France

CHU de Limoges

Limoges, , France

Hospices Civils de Lyon

Lyon, , France

CHU de Montpellier

Montpellier, , France

CHRU Nancy

Nancy, , France

CHU de Nantes

Nantes, , France

Hôpital Bicêtre

Paris, , France

GHU Paris Psychiatrie et Neurosciences, Sainte Anne

Paris, , France

Fondation Ophtalmologique A. de Rothschild

Paris, , France

CHU Rouen Normandie

Rouen, , France

CHRU Strasbourg

Strasbourg, , France

CHU de Toulouse

Toulouse, , France

CHU Tours

Tours, , France

Hôpital Foch

Suresnes, Île-de-France Region, France

Universitätsmedizin Mannheim, Universität Heidelber

Mannheim, Baden-Wurttemberg, Germany

Klinikum Osnabrück GmbH

Osnabrück, Lower Saxony, Germany

Universitätsklinikum RWTH Aachen

Aachen, North Rhine-Westphalia, Germany

Universitätsklinikum Schleswig-Holstein, Campus Kiel

Kiel, Schleswig-Holstein, Germany

Universitätsklinikum Knappschaftskrankenhaus GmbH Bochum

Bochum, , Germany

Universitätsklinikum Frankfurt

Frankfurt, , Germany

Universitätsmedizin Göttingen

Göttingen, , Germany

Medizinische Fakultät der Otto-von-Guericke-Universität Magdeburg

Magdeburg, , Germany

Klinikum rechts der Isar der Technischen Universität München

München, , Germany

Klinikum Vest GmbH

Recklinghausen, , Germany

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitari Germans Trias i Pujol

Barcelona, , Spain

Dept. of Neurology, Kantonsspital Aarau

Aarau, Canton of Aargau, Switzerland

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

Lausanne, Canton of Vaud, Switzerland

Dept. of Neurology, Ospedale Civo of Lugano

Lugano, Canton Ticino, Switzerland

Dept. of Neurology, Bern University Hospital

Bern, , Switzerland

Hôpitaux Universitaires de Genève - HUG

Geneva, , Switzerland

Kantonsspital St.Gallen

Sankt Gallen, , Switzerland

Dept. of Neuroradiology, UniversitätsSpital Zürich

Zurich, , Switzerland

Belfast City Hospital

Belfast, , United Kingdom

St George's University Hospitals NHS Foundation Trust

London, , United Kingdom

Salford Royal

Salford, , United Kingdom

Countries

Austria; Canada; Finland; France; Germany; Spain; Switzerland; United Kingdom

References

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Reference Type: DERIVED

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Reference Type: DERIVED

PMID: 36396433 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35902234 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35810756 (View on PubMed)

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.

Reference Type: DERIVED

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Related Links

http://www.swift-direct.com/

Trial Website

Other Identifiers

2017-00974

Identifier Type: -

Identifier Source: org_study_id