Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial
Background and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outc...
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Korean Stroke Society
2025-01-01
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| Series: | Journal of Stroke |
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| Online Access: | http://j-stroke.org/upload/pdf/jos-2024-03139.pdf |
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| author | Mayank Goyal Bijoy K. Menon Johanna Ospel Mohammed Almekhlafi Charlotte Zerna Raul Nogueira Ryan McTaggart Andrew M. Demchuk Alexandre Y. Poppe Brian Buck Kathy Heard Manish Joshi Diogo Haussen Shawna Cutting Shelagh B. Coutts Daniel Roy Jeremy L. Rempel Thalia S. Field Dar Dowlatshahi Brian van Adel Richard Swartz Ruchir Shah Eric Sauvageau Volker Puetz Frank L. Silver Bruce Campbell René Chapot Michael Tymianski Michael D. Hill on Behalf of the ESCAPE-NA1 Investigators |
| author_facet | Mayank Goyal Bijoy K. Menon Johanna Ospel Mohammed Almekhlafi Charlotte Zerna Raul Nogueira Ryan McTaggart Andrew M. Demchuk Alexandre Y. Poppe Brian Buck Kathy Heard Manish Joshi Diogo Haussen Shawna Cutting Shelagh B. Coutts Daniel Roy Jeremy L. Rempel Thalia S. Field Dar Dowlatshahi Brian van Adel Richard Swartz Ruchir Shah Eric Sauvageau Volker Puetz Frank L. Silver Bruce Campbell René Chapot Michael Tymianski Michael D. Hill on Behalf of the ESCAPE-NA1 Investigators |
| author_sort | Mayank Goyal |
| collection | DOAJ |
| description | Background and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups. Methods ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model. Results Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome. Conclusion Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles. |
| format | Article |
| id | doaj-art-a97f2799c8824e1785d2d9ca3c783f8f |
| institution | DOAJ |
| issn | 2287-6391 2287-6405 |
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| publishDate | 2025-01-01 |
| publisher | Korean Stroke Society |
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| spelling | doaj-art-a97f2799c8824e1785d2d9ca3c783f8f2025-08-20T03:03:08ZengKorean Stroke SocietyJournal of Stroke2287-63912287-64052025-01-012719510110.5853/jos.2024.03139564Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 TrialMayank Goyal0Bijoy K. Menon1Johanna Ospel2Mohammed Almekhlafi3Charlotte Zerna4Raul Nogueira5Ryan McTaggart6Andrew M. Demchuk7Alexandre Y. Poppe8Brian Buck9Kathy Heard10Manish Joshi11Diogo Haussen12Shawna Cutting13Shelagh B. Coutts14Daniel Roy15Jeremy L. Rempel16Thalia S. Field17Dar Dowlatshahi18Brian van Adel19Richard Swartz20Ruchir Shah21Eric Sauvageau22Volker Puetz23Frank L. Silver24Bruce Campbell25René Chapot26Michael Tymianski27Michael D. Hill28on Behalf of the ESCAPE-NA1 Investigators Department of Diagnostic Imaging, Cumming School of Medicine, University of Calgary, Calgary, Canada Department of Diagnostic Imaging, Cumming School of Medicine, University of Calgary, Calgary, Canada Department of Diagnostic Imaging, Cumming School of Medicine, University of Calgary, Calgary, Canada Department of Diagnostic Imaging, Cumming School of Medicine, University of Calgary, Calgary, Canada Städtisches Klinikum Dresden, Dresden, Germany Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Warren Alpert School of Medicine, Brown University, Providence, RI, USA Department of Diagnostic Imaging, Cumming School of Medicine, University of Calgary, Calgary, Canada Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada University of Alberta Hospital, Edmonton, Alberta, Canada NoNO Inc., Toronto, Canada Department of Diagnostic Imaging, Cumming School of Medicine, University of Calgary, Calgary, Canada NoNO Inc., Toronto, Canada Warren Alpert School of Medicine, Brown University, Providence, RI, USA Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Canada Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada University of Alberta Hospital, Edmonton, Alberta, Canada University of British Columbia, Vancouver, BC, Canada Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada McMaster University, Hamilton, ON, Canada Sunnybrook Health Sciences Centre, Toronto, Canada Erlanger Hospital, Chattanooga, TN, USA Lyerly Neurosurgery, Baptist Hospital, Jacksonville, FL, USA University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden Neurovascular Center, Dresden, Germany University Health Network, University of Toronto, Toronto, Canada The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia Neuroradiology, Alfried Krupp Krankenhaus, Essen, Germany NoNO Inc., Toronto, Canada Department of Diagnostic Imaging, Cumming School of Medicine, University of Calgary, Calgary, CanadaBackground and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups. Methods ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model. Results Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome. Conclusion Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.http://j-stroke.org/upload/pdf/jos-2024-03139.pdfacute ischemic strokethrombectomyneuroprotectioncerebroprotectionnerinetide |
| spellingShingle | Mayank Goyal Bijoy K. Menon Johanna Ospel Mohammed Almekhlafi Charlotte Zerna Raul Nogueira Ryan McTaggart Andrew M. Demchuk Alexandre Y. Poppe Brian Buck Kathy Heard Manish Joshi Diogo Haussen Shawna Cutting Shelagh B. Coutts Daniel Roy Jeremy L. Rempel Thalia S. Field Dar Dowlatshahi Brian van Adel Richard Swartz Ruchir Shah Eric Sauvageau Volker Puetz Frank L. Silver Bruce Campbell René Chapot Michael Tymianski Michael D. Hill on Behalf of the ESCAPE-NA1 Investigators Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial Journal of Stroke acute ischemic stroke thrombectomy neuroprotection cerebroprotection nerinetide |
| title | Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial |
| title_full | Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial |
| title_fullStr | Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial |
| title_full_unstemmed | Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial |
| title_short | Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial |
| title_sort | factors influencing nerinetide effect on clinical outcome in patients without alteplase treatment in the escape na1 trial |
| topic | acute ischemic stroke thrombectomy neuroprotection cerebroprotection nerinetide |
| url | http://j-stroke.org/upload/pdf/jos-2024-03139.pdf |
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