{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:45:46Z","timestamp":1787323546578,"version":"build-2736575974"},"reference-count":16,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"unspecified","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Self-initiated Research Project of General Hospital of the Northern Theater Command","award":["ZZKY2024014"],"award-info":[{"award-number":["ZZKY2024014"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,8,10]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Recanalisation rates following standard intravenous thrombolysis (IVT) for acute ischaemic stroke due to medium or large vessel occlusion (MeVO\/LVO) remain unsatisfactory, leading to poor clinical outcomes. Tenecteplase (TNK), a fibrin-specific thrombolytic agent, demonstrates potential advantages over alteplase, including higher recanalisation rates in LVO. Preliminary evidence suggests that a second dose of thrombolytic in patients with persistent vessel occlusion after initial IVT may be feasible and beneficial. This study aims to evaluate the efficacy and safety of a second intravenous dose of TNK administered to patients with acute anterior and posterior circulation MeVO\/LVO who have not recanalised 1\u2009hour after standard IVT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>RITIS-TNK2 is a prospective, randomised, open-label, blinded endpoint, multicentre, superiority trial. Eligible patients will be randomly assigned (1:1) to receive a second dose of TNK (0.25\u2009mg\/kg intravenously, capped at a maximum total dose of 16\u2009mg) plus standard medical care or standard medical care alone. The primary efficacy outcome is the recanalisation rate of the occluded artery at 24 hours after randomisation. The primary safety outcome is symptomatic intracranial haemorrhage within 24 hours. Secondary outcomes include functional status at 90 days (modified Rankin Scale score). The expected recanalisation rate at 24 hours in the control group is estimated at 45%. We hypothesise rescue TNK will raise 24-hour recanalisation rate from 45% to 65%, representing an absolute 20 percentage-point improvement and a relative 44.4% increase. A maximum of 198 patients are required to test the superiority hypothesis with 80% power according to a two-sided 0.05 level of significance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study has been approved by the central Institutional Review Board (General Hospital of Northern Theater Command; IRB: Y (2025) 502). The study results will be disseminated through peer-reviewed journals and presentation at relevant national and international scientific conferences, regardless of the direction of the findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT07375966\">NCT07375966<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-120918","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:08:32Z","timestamp":1787321312000},"page":"e120918","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Repeated intravenous thrombolysis for ischaemic stroke with medium to large vessel occlusion presenting within 4.5 hours of onset with tenecteplase in China (RITIS-TNK2): protocol for a prospective, randomised, open-label, blinded assessment of outcome and multicentre study"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct07375966","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct07375966","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04588337","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Zhi-Guo","family":"Yao","sequence":"first","affiliation":[{"name":"General Hospital of Northern Theater Command, Shenyang, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Rui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Han","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong-He","family":"Zhou","sequence":"additional","affiliation":[{"name":"General Hospital of Northern Theater Command, Shenyang, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7486-1992","authenticated-orcid":false,"given":"Hui-Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, General Hospital of Northern Theater Command, 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