{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:36:04Z","timestamp":1792586164806,"version":"4.5.0"},"reference-count":29,"publisher":"American Medical Association (AMA)","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2026,6,9]]},"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Although recent trials have shown benefit with early tirofiban after thrombolysis, its efficacy remains uncertain in patients with acute ischemic stroke who do not have a large or medium vessel occlusion or a cardioembolic source and who show an inadequate clinical response to intravenous tenecteplase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the efficacy and safety of intravenous tirofiban administered after an inadequate response to intravenous tenecteplase in this specific patient population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>Investigator-initiated, randomized, double-blind, placebo-controlled trial conducted at 37 hospitals in China, enrolling 359 patients with acute ischemic stroke, without large or medium vessel occlusion or cardioembolic etiology, and with an insufficient clinical response to intravenous tenecteplase (defined as no significant change from baseline, neurological deterioration, or neurological fluctuation based on serial assessment of the National Institutes of Health Stroke Scale score within 4-24 hours after infusion). Recruitment took place between April 24, 2024, and July 16, 2025, with final follow-up on October 11, 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Intravenous tirofiban (n\u2009=\u2009177), administered as a 0.3-\u03bcg\/kg\/min bolus over 30 minutes, followed by a continuous infusion of 0.075 \u03bcg\/kg\/min for up to 47.5 hours, or matching placebo (n\u2009=\u2009182), initiated within 4 to 24 hours after intravenous tenecteplase. Oral antiplatelet therapy (aspirin and\/or clopidogrel) was started 24 hours after thrombolysis in the placebo group and 44 hours after thrombolysis in the tirofiban group and continued in all patients through 90-day follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>The primary outcome was an excellent outcome (defined as a score of 0 or 1 on the modified Rankin Scale; range, 0-6, with higher scores indicating more severe disability) at 90 days. Safety outcomes included incidence of symptomatic intracranial hemorrhage within 48 hours and 90-day mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 359 patients randomized (mean age, 66 years; 141 females [39.3%]), 358 (99.7%) completed the trial. An excellent outcome at 90 days was observed in 113 patients (63.8%) in the tirofiban group and in 95 patients (52.2%) in the placebo group (risk ratio, 1.22; 95% CI, 1.02-1.46;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.03). Symptomatic intracranial hemorrhage within 48 hours occurred in 1 patient (0.9%) in the tirofiban group and no patients in the placebo group; 90-day mortality was 0.6% and 1.6%, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Among patients with acute ischemic stroke without large or medium vessel occlusion or a cardioembolic source who had an inadequate clinical response to intravenous tenecteplase, adjunctive intravenous tirofiban increased the likelihood of an excellent outcome at 90 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/study\/NCT05604638\">NCT05604638<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jama.2026.5245","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T11:30:19Z","timestamp":1778239819000},"page":"1949","source":"Crossref","is-referenced-by-count":7,"title":["Intravenous Tirofiban After Tenecteplase in Acute Ischemic Stroke"],"prefix":"10.1001","volume":"335","author":[{"name":"INSTANT Trial Authors for the INSTANT Investigators","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Ganzhou Hospital of Nanchang University (Ganzhou People\u2019s Hospital), Ganzhou, China"},{"name":"Ganzhou Hospital-Nanfang Hospital, Southern Medical University (Ganzhou People\u2019s Hospital), Ganzhou, 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