{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:38:04Z","timestamp":1786451884095,"version":"build-2736575974"},"reference-count":27,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"unspecified","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002402","name":"Sun Yat-sen University","doi-asserted-by":"publisher","award":["2025015"],"award-info":[{"award-number":["2025015"]}],"id":[{"id":"10.13039\/501100002402","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,7,30]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The coronary slow-flow\/no-reflow phenomenon adversely affects clinical outcomes following percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS), demonstrating a substantial association with increased cardiovascular mortality and heart failure incidence. Despite its significant clinical implications, current therapeutic strategies for this condition lack robust guideline recommendations and are not supported by large-scale clinical evidence. Intracoronary administration of recombinant human prourokinase, a novel fibrin-specific thrombolytic, demonstrates potential for improving microvascular dysfunction through targeted fibrinolysis. Nevertheless, current evidence is limited to small-scale clinical studies, lacking large-scale trials to guideline recommendations. This study aims to investigate whether selective intracoronary administration of prourokinase, in addition to conventional intensive antiplatelet therapy, nitrates and calcium channel blockers, can reduce the incidence of cardiovascular events at 12 months post-PCI in patients with ACS experiencing slow flow\/no-reflow during the procedure without increasing the incidence of major bleeding events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a randomised, double-blind, placebo-controlled study to evaluate the efficacy of low-dose intracoronary administration of prourokinase or placebo via a microcatheter in the infarct-related artery in patients with ACS with slow flow\/no-reflow during PCI. The primary endpoint is the incidence of major adverse cardiovascular events (MACE) 12 months after the intervention, defined as the composite of cardiovascular death, recurrent myocardial infarction, hospitalisation for unstable angina, unplanned repeat revascularisation, hospitalisation for heart failure or non-fatal stroke, whichever occurs first. Secondary endpoints include myocardial reperfusion (thrombolysis in myocardial infarction (TIMI) flow grade, TIMI frame count), myocardial infarction severity (ST-segment resolution, infarct area estimated from area under the curve of cardiac troponin T), angina severity (Canadian Cardiovascular Society grading of angina pectoris), cardiac function (left ventricular ejection fraction, New York Heart Association functional classification) and short-term MACE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics<\/jats:title>\n                    <jats:p>This study will adhere to the principles outlined in the Declaration of Helsinki and other applicable ethical guidelines. The study protocol has been approved by the Medical Research Ethics Committee of Sun Yat-sen Memorial Hospital of Sun Yat-sen University (Approval No: SYSKY-2024-735-04).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Dissemination<\/jats:title>\n                    <jats:p>We will disseminate findings via peer-reviewed journals, international conferences and stakeholder outreach (clinicians, policymakers and patients), supplemented by digital platforms to accelerate knowledge translation and clinical implementation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ChiCTR2500103336.<\/jats:p>\n                  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