Bridging Thrombolysis Versus Direct Mechanical Thrombectomy in Acute Ischemic Stroke (SWIFT DIRECT)

March 6, 2023 updated by: University Hospital Inselspital, Berne

Solitaire™ With the Intention For Thrombectomy Plus Intravenous t-PA Versus DIRECT Solitaire™ Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

410

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
        • Medical University of Innsbruck
    • Oberösterreich
      • Linz, Oberösterreich, Austria, 4020
        • Keppler Universitätsklinikum
  • Canada
      • Calgary, Canada
        • University of Calgary, Alberta Health Services
      • Montréal, Canada
        • Mc Gill University
      • Saskatoon, Canada
        • Royal University Hospital, University of Saskatchewan
      • Toronto, Canada
        • Toronto Western Hospital
  • Finland
      • Helsinki, Finland, 00290
        • Helsinki University Hospital
  • France
      • Bordeaux, France, 33404
        • CHU de Bordeaux
      • Caen, France, 14033
        • Chu de Caen Normandie
      • Lille, France, 59037
        • CHU de Lille
      • Limoges, France, 87042
        • CHU de Limoges
      • Lyon, France, 69002
        • Hospices Civils de Lyon
      • Montpellier, France
        • CHU de Montpellier
      • Nancy, France, 54035
        • CHRU Nancy
      • Nantes, France, 44093
        • CHU de Nantes
      • Paris, France, 75019
        • Fondation Ophtalmologique A. de Rothschild
      • Paris, France, 75010
        • Hôpital Bicêtre
      • Paris, France, 75014
        • GHU Paris Psychiatrie et Neurosciences, Sainte Anne
      • Rouen, France, 76031
        • CHU Rouen Normandie
      • Strasbourg, France, 67091
        • CHRU Strasbourg
      • Toulouse, France, 31059
        • CHU de Toulouse
      • Tours, France, 37044
        • CHU Tours
    • Finistère
      • Brest, Finistère, France, 29200
        • Hôpital Cavale Blanche CHU Brest
    • Marne
      • Reims, Marne, France, 51100
        • CHU de Reims
    • Puy-de-Dôme
      • Clermont-Ferrand, Puy-de-Dôme, France, 63000
        • CHU de Clermont-Ferrand
    • Île De France
      • Suresnes, Île De France, France, 92150
        • Hopital FOCH
  • Germany
      • Bochum, Germany
        • Universitätsklinikum Knappschaftskrankenhaus GmbH Bochum
      • Frankfurt, Germany, 60528
        • Universitatsklinikum Frankfurt
      • Göttingen, Germany, 37075
        • Universitätsmedizin Göttingen
      • Magdeburg, Germany
        • Medizinische Fakultät der Otto-von-Guericke-Universität Magdeburg
      • München, Germany
        • Klinikum rechts der Isar der Technischen Universität München
      • Recklinghausen, Germany
        • Klinikum Vest GmbH
    • Baden-Württemberg
      • Mannheim, Baden-Württemberg, Germany, 68167
        • Universitätsmedizin Mannheim, Universität Heidelber
    • Niedersachsen
      • Osnabrück, Niedersachsen, Germany, 49076
        • Klinikum Osnabrück GmbH
    • Nordrhein-Westfalen
      • Aachen, Nordrhein-Westfalen, Germany, 52074
        • Universitätsklinikum RWTH Aachen
    • Schleswig-Holstein
      • Kiel, Schleswig-Holstein, Germany, 24105
        • Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08916
        • Hospital Universitari Germans Trias i Pujol
  • Switzerland
      • Bern, Switzerland, 3010
        • Dept. of Neurology, Bern University Hospital
      • Geneva, Switzerland, 1211
        • Hopitaux Universitaires de Geneve - HUG
      • Saint Gallen, Switzerland, 9007
        • Kantonsspital St.Gallen
      • Zürich, Switzerland, 8091
        • Dept. of Neuroradiology, UniversitätsSpital Zürich
    • Aargau
      • Aarau, Aargau, Switzerland, 5001
        • Dept. of Neurology, Kantonsspital Aarau
    • Ticino
      • Lugano, Ticino, Switzerland, 6900
        • Dept. of Neurology, Ospedale Civo of Lugano
    • Vaud
      • Lausanne, Vaud, Switzerland, 1011
        • Dept. of Neurology, Centre hospitalier universitaire vaudois (CHUV)
  • United Kingdom
      • Belfast, United Kingdom
        • Belfast City Hospital
      • London, United Kingdom
        • St George's University Hospitals NHS Foundation Trust
      • Salford, United Kingdom
        • Salford Royal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Direct mechanical thrombectomy
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
Mechanical thrombectomy with a stent-retriever revascularization device
Active Comparator: 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.
Device: Stent-retriever thrombectomy with revascularization device of the Solitaire™ type
Mechanical thrombectomy with a stent-retriever revascularization device
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Score in modified Rankin Scale (mRS)
Time Frame: 90 days after randomization
90 days after randomization

Secondary Outcome Measures

Outcome Measure
Time Frame
Mortality
Time Frame: 90 days after randomization
90 days after randomization
Modified Rankin Scale (mRS) shift analysis
Time Frame: day 0 and 90 days after randomization
day 0 and 90 days after randomization
National Institute of Health Score Scale (NIHSS)
Time Frame: day 0 and day 1 after randomization
day 0 and day 1 after randomization
Thrombolysis in Cerebral Infarction (TICI) scale
Time Frame: day 0 and day 1 after randomization
day 0 and day 1 after randomization
Serious adverse events
Time Frame: day 0 until 90 days after randomization
day 0 until 90 days after randomization
Intracranial hemorrhage
Time Frame: day 1 after randomization
day 1 after randomization
Quality of life assessed by questionnaire
Time Frame: 90 days after randomization
90 days after randomization
Overall costs incurred during hospitalisation
Time Frame: 90 days after randomization
90 days after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Inselspital, Berne

Collaborators

Medtronic

Investigators

  • Principal Investigator: Urs Fischer, Prof. Dr., Dept. of Neurology, Inselspital Bern
  • Principal Investigator: Jan Gralla, Prof. Dr., Dept. of Neuroradiology, Inselspital Bern

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 29, 2017

Primary Completion (Actual)

May 14, 2021

Study Completion (Actual)

August 11, 2021

Study Registration Dates

First Submitted

June 12, 2017

First Submitted That Met QC Criteria

June 15, 2017

First Posted (Actual)

June 20, 2017

Study Record Updates

Last Update Posted (Estimate)

March 7, 2023

Last Update Submitted That Met QC Criteria

March 6, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017-00974

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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