{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T14:31:37Z","timestamp":1793802697237,"version":"4.6.1"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Nerinetide is a neuroprotective agent recently evaluated in the ESCAPE\u2010NEXT (Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis) trial (NCT04462536), which was terminated after failing to meet its Day 90 primary end point; however, by that time, Year 1 follow\u2010up outcomes were already available for 513 participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">The primary end point at Year 1 was functional independence, defined as modified Rankin Scale score 0 to 2, analyzed by logistic regression adjusted for treatment and baseline covariates. In a post hoc analysis, the interaction between early (&lt;3\u2009hours) versus late (3\u201312\u2009hours) enrollment window and treatment effect was also tested and the results reported separately by enrollment window.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      A total of 513 of 850 participants had documented Year 1 outcomes before study termination, of whom 442 reached their scheduled Year 1 visit. In the nerinetide group, 110 (48.0%) of 229 participants achieved functional independence at Year 1 compared with 102 (47.9%) of 213 in the placebo group (adjusted odds ratio [\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">aOR<\/jats:styled-content>\n                      ], 1.12 [95%\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">CI,<\/jats:styled-content>\n                      0.74\u20131.71];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.593). There was treatment effect modification by enrollment window (early versus late;\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      =0.044). Among early window participants (n=163), 51 (52.6%) in the nerinetide group and 30 (45.5%) in placebo achieved functional independence (\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">aOR,<\/jats:styled-content>\n                      2.80 [95%\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">CI,<\/jats:styled-content>\n                      1.18\u20136.66],\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.019) at Year 1. Additionally, the nerinetide group exhibited improved survival (\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">aOR,<\/jats:styled-content>\n                      2.61 [95%\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">CI,<\/jats:styled-content>\n                      1.17\u20135.83],\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.019). Conversely, no significant clinical benefit of nerinetide at Year 1 was observed among late window participants. Analyses on all 513 participants with documented Year 1 outcomes provided similar results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Long\u2010term benefits of early administration of neuroprotection may emerge up to 1\u2009year after stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.044080","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:32:48Z","timestamp":1782210768000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Safety and Efficacy of Nerinetide at Year 1 in Participants Enrolled in ESCAPE\u2010NEXT: A Multicenter, Double\u2010Blind, Randomized Controlled 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Calgary","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6297-3153","authenticated-orcid":false,"given":"Jorg","family":"Berrouschot","sequence":"additional","affiliation":[{"name":"Klinikum Altenburger Land, Neurology","place":["Altenburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7984-6062","authenticated-orcid":false,"given":"Brian","family":"Buck","sequence":"additional","affiliation":[{"name":"University of Alberta Hospital","place":["Edmonton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4930-7789","authenticated-orcid":false,"given":"Andrew","family":"Demchuk","sequence":"additional","affiliation":[{"name":"University of Calgary","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9234-3515","authenticated-orcid":false,"given":"Diederik","family":"Dippel","sequence":"additional","affiliation":[{"name":"Erasmus MC University Medical Center Rotterdam","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9093-8307","authenticated-orcid":false,"given":"Franziska","family":"Dorn","sequence":"additional","affiliation":[{"name":"University of Bonn","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1176-0633","authenticated-orcid":false,"given":"Thalia","family":"Field","sequence":"additional","affiliation":[{"name":"University of British Columbia","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Muto","sequence":"additional","affiliation":[{"name":"Antonio 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