From the start this is bad research; looking for noninferior outcomes rather than 100% recovery. THIS IS WHY SURVIVORS NEED TO BE IN CHARGE. We would never approve such crapola.
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
Urs Fischerhttps://orcid.org/0000-0003-0521-40511, Johannes Kaesmacherhttps://orcid.org/0000-0002-9177-22892, Patricia S Plattner2, Lukas Bütikofer3, Pasquale Mordasini2, Sandro Deppeler2, Christoph Cognard4, Vitor M Pereira5, Adnan H Siddiqui6, Michael T Froehler7, Anthony J Furlan8, René Chapot9, Daniel Strbian10, Martin Wiesmann11, Jenny Bressanhttps://orcid.org/0000-0002-5078-569X1, Stefanie Lerchhttps://orcid.org/0000-0002-9929-92891, David S Liebeskind13, Jeffery L Saver12, Jan Gralla2, and on behalf of the SWIFT DIRECT study investigators
Rationale
Whether treatment with intravenous alteplase prior to mechanical thrombectomy (MT) in acute ischemic stroke patients with large vessel occlusion is beneficial remains unclear.
Aim
To determine whether patients experiencing acute ischemic stroke due to occlusion of the intracranial internal carotid artery or the M1 segment of the middle cerebral artery who are referred to an endovascular stroke center and who are candidates for intravenous alteplase will have non-inferior functional outcome at 90 days when treated with MT alone (direct MT) with stent retrievers compared to patients treated with combined intravenous thrombolysis (IVT) with alteplase plus MT (IVT + MT) with stent retrievers.
Sample sizeTo randomize 404 patients 1:1 to direct MT or combined IVT+MT.
Sample sizeTo randomize 404 patients 1:1 to direct MT or combined IVT+MT.
Methods and design
A multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial utilizing an adaptive statistical design.
Outcomes
The primary efficacy endpoint is functional independence (modified Rankin Scale 0–2) at 90 days. Secondary clinical efficacy outcomes include change in National Institutes of Health Stroke Scale score from baseline to day 1 and health-related quality of life at 90 days. Secondary technical efficacy outcomes include successful reperfusion prior to start of MT and time from randomization to successful reperfusion. Safety outcomes include all serious adverse events, symptomatic intracranial hemorrhage, and mortality up to 90 days.
Discussion
SWIFT DIRECT will inform physicians whether direct MT in acute ischemic stroke patients with large vessel occlusion is equally or more efficacious than combined treatment with intravenous alteplase and MT.
Trial registrationClinicalTrials.gov Identifier: NCT03192332
Keywords
Ischemic stroke, large vessel occlusion, alteplase, stent retriever
1Department of Neurology, University Hospital and University of Bern, Bern, Switzerland
2Institute of Diagnostic and Interventional Neuroradiology, University Hospital and University of Bern, Bern, Switzerland
3CTU Bern, University of Bern, Bern, Switzerland
4Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Toulouse, Toulouse, France
5Division of Neuroradiology and Division of Neurosurgery, Departments of Medical Imaging and Surgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Canada
6Department of Neurosurgery and Toshiba Stroke and Vascular Research Center, State University of New York at Buffalo, Buffalo, USA
7Vanderbilt Cerebrovascular Program, Vanderbilt University Medical Center, Nashville, USA
8School of Medicine, Case Western Reserve University, Cleveland, OH, USA
9Department of Intracranial Endovascular Therapy, Alfried Krupp Krankenhaus Essen, Essen, Germany
10Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
11Department of Neuroradiology, University Hospital RWTH Aachen, Aachen, Germany
12Department of Neurology and Comprehensive Stroke Center, David Geffen School of Medicine, University of California, Los Angeles, USA
13Department of Neurology and UCLA Stroke Center, Los Angeles, California, USA
Corresponding author(s):
Urs Fischer, Department of Neurology, Inselspital, Freiburgstrasse 8, CH-3010 Bern, Switzerland. Email: urs.fischer@insel.ch
Introduction and rationale
Randomized-controlled studies have shown that patients with an acute ischemic stroke (AIS) with a large vessel occlusion (LVO) in the anterior circulation who are eligible for intravenous thrombolysis (IVT) with alteplase benefit more from mechanical thrombectomy (MT) following IVT than from IVT alone.1 However, as all these studies evaluated MT on the background of administering IVT to IVT-eligible patients, they did not address, in a randomized fashion, whether IVT before MT adds additional benefit compared with direct MT alone.2–4 An individual patient data meta-analysis comparing use versus non-use of MT in IVT-eligible patients treated with IVT+MT with use versus non-use of MT in IVT-ineligible patients treated with direct MT found no significant difference in the treatment benefit conferred by MT.1
IVT prior to MT may benefit patients by yielding faster reperfusion, before MT device placement, by conditioning thrombi to respond better to MT resulting in more frequent endovascular clot removal, and by dissolving residual or newly embolized thrombi in distal vessels beyond device reach.2 Conversely, IVT prior to MT may harm patients by causing clot fragmentation and distal embolization beyond device reach before the start of device treatment and by increasing the risk of symptomatic intra- and extracranial haemorrhage.2 Furthermore, the benefit from fast reperfusion with IVT alone is constrained by the low responsiveness of LVO thrombi to systemic lytic treatment. In a large cohort study, rates of pre-interventional reperfusion with IVT in directly admitted patients with occlusions of the intracranial internal carotid artery (ICA) or M1 segment of the middle cerebral artery (MCA) were low.5
Several meta-analyses compared direct MT with IVT+MT in observational series.6,7 However, these meta-analyses are prone to selection bias and results are conflicting. Therefore, randomized trial evidence is needed to demonstrate whether direct MT in patients with anterior circulation LVO is equally or more efficacious than IVT+MT.
Trial registrationClinicalTrials.gov Identifier: NCT03192332
Keywords
Ischemic stroke, large vessel occlusion, alteplase, stent retriever
1Department of Neurology, University Hospital and University of Bern, Bern, Switzerland
2Institute of Diagnostic and Interventional Neuroradiology, University Hospital and University of Bern, Bern, Switzerland
3CTU Bern, University of Bern, Bern, Switzerland
4Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Toulouse, Toulouse, France
5Division of Neuroradiology and Division of Neurosurgery, Departments of Medical Imaging and Surgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Canada
6Department of Neurosurgery and Toshiba Stroke and Vascular Research Center, State University of New York at Buffalo, Buffalo, USA
7Vanderbilt Cerebrovascular Program, Vanderbilt University Medical Center, Nashville, USA
8School of Medicine, Case Western Reserve University, Cleveland, OH, USA
9Department of Intracranial Endovascular Therapy, Alfried Krupp Krankenhaus Essen, Essen, Germany
10Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
11Department of Neuroradiology, University Hospital RWTH Aachen, Aachen, Germany
12Department of Neurology and Comprehensive Stroke Center, David Geffen School of Medicine, University of California, Los Angeles, USA
13Department of Neurology and UCLA Stroke Center, Los Angeles, California, USA
Corresponding author(s):
Urs Fischer, Department of Neurology, Inselspital, Freiburgstrasse 8, CH-3010 Bern, Switzerland. Email: urs.fischer@insel.ch
Introduction and rationale
Randomized-controlled studies have shown that patients with an acute ischemic stroke (AIS) with a large vessel occlusion (LVO) in the anterior circulation who are eligible for intravenous thrombolysis (IVT) with alteplase benefit more from mechanical thrombectomy (MT) following IVT than from IVT alone.1 However, as all these studies evaluated MT on the background of administering IVT to IVT-eligible patients, they did not address, in a randomized fashion, whether IVT before MT adds additional benefit compared with direct MT alone.2–4 An individual patient data meta-analysis comparing use versus non-use of MT in IVT-eligible patients treated with IVT+MT with use versus non-use of MT in IVT-ineligible patients treated with direct MT found no significant difference in the treatment benefit conferred by MT.1
IVT prior to MT may benefit patients by yielding faster reperfusion, before MT device placement, by conditioning thrombi to respond better to MT resulting in more frequent endovascular clot removal, and by dissolving residual or newly embolized thrombi in distal vessels beyond device reach.2 Conversely, IVT prior to MT may harm patients by causing clot fragmentation and distal embolization beyond device reach before the start of device treatment and by increasing the risk of symptomatic intra- and extracranial haemorrhage.2 Furthermore, the benefit from fast reperfusion with IVT alone is constrained by the low responsiveness of LVO thrombi to systemic lytic treatment. In a large cohort study, rates of pre-interventional reperfusion with IVT in directly admitted patients with occlusions of the intracranial internal carotid artery (ICA) or M1 segment of the middle cerebral artery (MCA) were low.5
Several meta-analyses compared direct MT with IVT+MT in observational series.6,7 However, these meta-analyses are prone to selection bias and results are conflicting. Therefore, randomized trial evidence is needed to demonstrate whether direct MT in patients with anterior circulation LVO is equally or more efficacious than IVT+MT.
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