Bridging Thrombolysis Versus Direct Mechanical Thrombectomy in Acute Ischemic Stroke

Ischemic Stroke Clinical Trial

— SWIFT DIRECT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03192332
• Other study ID #: 2017-00974
• Status: Completed
• Phase: N/A
• Start date: November 29, 2017
• Est. completion date: August 11, 2021

Study information

• Verified date: March 2023
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 410
• Est. completion date: August 11, 2021
• Est. primary completion date: May 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ischemia
• Ischemic Stroke
• Stroke

Intervention

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.

Locations

Country	Name	City	State
Austria	Medical University of Innsbruck	Innsbruck
Austria	Keppler Universitätsklinikum	Linz	Oberösterreich
Canada	University of Calgary, Alberta Health Services	Calgary
Canada	Mc Gill University	Montréal
Canada	Royal University Hospital, University of Saskatchewan	Saskatoon
Canada	Toronto Western Hospital	Toronto
Finland	Helsinki University Hospital	Helsinki
France	CHU de Bordeaux	Bordeaux
France	Hôpital Cavale Blanche CHU Brest	Brest	Finistère
France	CHU de Caen Normandie	Caen
France	CHU de Clermont-Ferrand	Clermont-Ferrand	Puy-de-Dôme
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	Fondation Ophtalmologique A. de Rothschild	Paris
France	GHU Paris Psychiatrie et Neurosciences, Sainte Anne	Paris
France	Hôpital Bicêtre	Paris
France	CHU de Reims	Reims	Marne
France	CHU Rouen Normandie	Rouen
France	CHRU Strasbourg	Strasbourg
France	Hôpital Foch	Suresnes	Île De France
France	CHU de Toulouse	Toulouse
France	CHU Tours	Tours
Germany	Universitätsklinikum RWTH Aachen	Aachen	Nordrhein-Westfalen
Germany	Universitätsklinikum Knappschaftskrankenhaus GmbH Bochum	Bochum
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel	Schleswig-Holstein
Germany	Medizinische Fakultät der Otto-von-Guericke-Universität Magdeburg	Magdeburg
Germany	Universitätsmedizin Mannheim, Universität Heidelber	Mannheim	Baden-Württemberg
Germany	Klinikum rechts der Isar der Technischen Universität München	München
Germany	Klinikum Osnabrück GmbH	Osnabrück	Niedersachsen
Germany	Klinikum Vest GmbH	Recklinghausen
Spain	Hospital Universitari Germans Trias i Pujol	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Switzerland	Dept. of Neurology, Kantonsspital Aarau	Aarau	Aargau
Switzerland	Dept. of Neurology, Bern University Hospital	Bern
Switzerland	Hôpitaux Universitaires de Genève - HUG	Geneva
Switzerland	Dept. of Neurology, Centre hospitalier universitaire vaudois (CHUV)	Lausanne	Vaud
Switzerland	Dept. of Neurology, Ospedale Civo of Lugano	Lugano	Ticino
Switzerland	Kantonsspital St.Gallen	Saint Gallen
Switzerland	Dept. of Neuroradiology, UniversitätsSpital Zürich	Zürich
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	St George's University Hospitals NHS Foundation Trust	London
United Kingdom	Salford Royal	Salford

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne	Medtronic

Countries where clinical trial is conducted

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

Outcome

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

External Links

•   Trial Website