{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:52:08Z","timestamp":1777888328644,"version":"3.51.4"},"reference-count":21,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2011,3,18]],"date-time":"2011-03-18T00:00:00Z","timestamp":1300406400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Stroke"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Reperfusion in ischemic stroke can be pursued by either systemic intravenous thrombolysis or endovascular treatment. However, systemic intravenous thrombolysis with alteplase within 4\u00b75\u2009h of symptom onset in selected patients is the only medication of proven efficacy. No randomized-controlled trials have so far compared the two modalities. To explore this, after a pilot phase, we started the SYNTHESIS Expansion trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To determine whether endovascular treatment (i.e., intra-arterial thrombolysis with alteplase \u2013 if necessary, associated to or substituted by mechanical clot disruption and\/or retrieval) compared with systemic intravenous thrombolysis with alteplase, administered according to European labelling, increases the proportion of independent survivors at three-months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>SYNTHESIS Expansion is an open-label, multicenter randomized-controlled trial, with blinded follow-up. Eligibility applies to; patients with symptomatic ischemic stroke, seen within 4\u00b75\u2009h of onset; being able to initiate intravenous alteplase immediately, and endovascular treatment as soon as possible (not later than six-hours of stroke onset). The study is pragmatically based on the \u2018uncertainty principle\u2019 between endovascular treatment and systemic intravenous thrombolysis for patients eligible for intravenous alteplase. There are no prespecified clinical or instrumental criteria to further select a patient, although investigators are left free to use them. Enrollment will be completed with 350 randomized patients. Primary analysis is on an intent-to-treat basis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study outcomes<\/jats:title>\n                    <jats:p>Primary: modified Rankin scale score of 0 or 1 at three-months. Secondary: neurological deficit seven-days after thrombolysis and the safety of the procedure on the basis of events reported within seven-days following thrombolysis \u2013 symptomatic cerebral hemorrhage, fatal and nonfatal stroke, death from any cause, neurological deterioration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/j.1747-4949.2011.00587.x","type":"journal-article","created":{"date-parts":[[2011,3,18]],"date-time":"2011-03-18T02:41:08Z","timestamp":1300416068000},"page":"259-265","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["SYNTHESIS Expansion: Design of a Nonprofit, Pragmatic, Randomized, Controlled Trial on the Best Fast-Track Endovascular Treatment Vs. Standard Intravenous Alteplase for Acute Ischemic Stroke"],"prefix":"10.1177","volume":"6","author":[{"given":"Alfonso","family":"Ciccone","sequence":"first","affiliation":[{"name":"Stroke Unit, Department of Neurosciences, Niguarda Ca' Granda Hospital, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Valvassori","sequence":"additional","affiliation":[{"name":"Neurointerventional Unit, Department of Neurosciences, Niguarda Ca' Granda Hospital, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Nichelatti","sequence":"additional","affiliation":[{"name":"Service of Biostatistics, Niguarda Ca' Granda Hospital, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the SYNTHESIS Expansion investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2011,3,18]]},"reference":[{"key":"bibr1-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60149-4"},{"key":"bibr2-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410320113"},{"key":"bibr3-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70182-6"},{"key":"bibr4-j.1747-4949.2011.00587.x","first-page":"1169","volume":"19","author":"Endo S","year":"1998","journal-title":"Am J Neuroradiol"},{"key":"bibr5-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000257304.21967.ba"},{"key":"bibr6-j.1747-4949.2011.00587.x","first-page":"1596","volume":"23","author":"Rabinstein AA","year":"2002","journal-title":"Am J Neuroradiol"},{"key":"bibr7-j.1747-4949.2011.00587.x","first-page":"79","volume":"17","author":"Tomsick T","year":"1996","journal-title":"Am J Neuroradiol"},{"key":"bibr8-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.29.1.4"},{"key":"bibr9-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000258112.14918.24"},{"key":"bibr10-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.21.2003"},{"key":"bibr11-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.488551"},{"key":"bibr12-j.1747-4949.2011.00587.x","first-page":"1772","volume":"24","author":"Friedman DP","year":"2003","journal-title":"Am J Neuroradiol"},{"key":"bibr13-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.106.465567"},{"key":"bibr14-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1136\/jnis.2009.001388"},{"key":"bibr15-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804656"},{"key":"bibr16-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199911043411901"},{"key":"bibr17-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-4949.2008.00151.x"},{"key":"bibr18-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.506196"},{"key":"bibr19-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1159\/000108505"},{"key":"bibr20-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.19.5.604"},{"key":"bibr21-j.1747-4949.2011.00587.x","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.492348"}],"container-title":["International Journal of Stroke"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1747-4949.2011.00587.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1111\/j.1747-4949.2011.00587.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1111\/j.1747-4949.2011.00587.x","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1111\/j.1747-4949.2011.00587.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:43:28Z","timestamp":1777610608000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1111\/j.1747-4949.2011.00587.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,18]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2011,6]]}},"alternative-id":["10.1111\/j.1747-4949.2011.00587.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1747-4949.2011.00587.x","relation":{},"ISSN":["1747-4930","1747-4949"],"issn-type":[{"value":"1747-4930","type":"print"},{"value":"1747-4949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3,18]]}}}