{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T20:06:42Z","timestamp":1789070802093,"version":"build-2803163510"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["SVIN"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p xml:lang=\"en\">A single dose of intravenous thrombolysis (IVT) is the only effective acute treatment for patients with ischemic stroke who do not qualify for endovascular thrombectomy. However, at least 50% of patients treated with only IVT remain disabled. Studies suggest that incomplete recanalization and reperfusion of the distal or microvasculature contribute to incomplete recovery after a single dose of IVT. Single IVT doses above the approved doses produce excessive bleeding. Another strategy might be to provide a more sustained lytic effect by administering a second dose of IVT. Tenecteplase (TNK) pharmacokinetics and preliminary data from clinical trials suggest a second full dose might be given safely 45 minutes after the first dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p xml:lang=\"en\">We propose a phase 2a preliminary safety study of a second dose of TNK given 45 to60 minutes after the first dose in 20 patients not responding to the first dose. Patients will be included if they qualify for and receive a first dose of TNK within 3 hours of symptom onset, do not qualify for thrombectomy, sign informed consent, have a National Institutes of Health Stroke Scale score \u22656 45 minutes later, no bleeding on a repeat computed tomography scan, and can receive the second TNK dose within 4.5 hours of onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p xml:lang=\"en\">Primary outcome will be symptomatic intracerebral hemorrhage (type 2 parenchymal hemorrhage or parenchymal hemorrhage remote from the area of infarction with neurological deterioration) or major systemic bleeding; secondary outcomes will include other definitions of intracerebral hemorrhage and modified Rankin Scale score at hospital discharge and 90 days after stroke. The study will be stopped, and dual full\u2010dose TNK therapy will be considered unsafe, if 4 symptomatic or major bleeding events occur.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p xml:lang=\"en\">We propose the first study of 2 sequential doses of TNK in patients with stroke. If successful, this study will be followed by a larger phase 2b controlled safety confirmation and pilot efficacy study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/svin.125.002022","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T07:34:41Z","timestamp":1758699281000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Administering a Second Dose of Intravenous Tenecteplase in Acute Ischemic Stroke: Rationale and Design of a Pilot Clinical Trial"],"prefix":"10.1161","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3667-4248","authenticated-orcid":false,"given":"James C.","family":"Grotta","sequence":"first","affiliation":[{"name":"Memorial Hermann Hospital","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60584-5"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01054-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.6.862"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.116.015414"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.124.048872"},{"key":"e_1_3_2_7_2","article-title":"Early tirofiban infusion after intravenous thrombolysis for stroke","author":"Tao C","year":"2025","unstructured":"Tao C, Liu T, Cui T, Liu J, Li Z, Ren Y, Zhao X, Xie F, Li J, Wang H, et\u00a0al. 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