The coronary slow‑flow/no‑reflow phenomenon that can occur during percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) is associated with substantially worse clinical outcomes, including increased cardiovascular mortality and a higher incidence of heart failure. Current therapeutic approaches to manage slow‑flow/no‑reflow lack strong guideline recommendations and are not supported by large‑scale randomized evidence. Small studies suggest benefit from targeted intravascular strategies but are insufficient to change practice.
Recombinant human prourokinase is a fibrin‑specific thrombolytic agent proposed to improve microvascular dysfunction through localized fibrinolysis. Intracoronary delivery via microcatheter targets the infarct‑related artery and may restore microcirculatory flow after embolization or microthrombus formation that contributes to no‑reflow. However, evidence for this approach is limited to small‑scale clinical investigations, and large randomized data are lacking.
This national multicentre clinical study protocol aims to determine whether selective intracoronary administration of low‑dose prourokinase, added to conventional intensive antiplatelet therapy, nitrates and calcium channel blockers, can reduce clinically meaningful cardiovascular events at 12 months in ACS patients who develop slow‑flow/no‑reflow during PCI, without increasing major bleeding.
The study is a randomized, double‑blind, placebo‑controlled trial conducted across multiple centres. Eligible patients are those undergoing PCI for ACS who develop slow‑flow or no‑reflow in the infarct‑related artery during the procedure. The protocol specifies intracoronary administration via a microcatheter at the time the phenomenon is identified.
All subjects receive standard background care for ACS and PCI, including intensive antiplatelet therapy as well as nitrates and calcium channel blockers, per the study protocol. Details on inclusion and exclusion criteria, enrolment targets, and centre participation were specified in the full protocol; these details were not reported in the summary provided here.
Patients are randomized in a double‑blind fashion to receive either low‑dose intracoronary prourokinase or matching placebo, delivered through a microcatheter positioned in the infarct‑related artery during PCI. The study design maintains blinding of investigators and participants to treatment allocation. The precise low‑dose regimen and administration protocol were described in the full protocol; dosage specifics were not reported in the available summary.
Concomitant therapy with intensive antiplatelet agents, nitrates and calcium channel blockers is provided to both arms to reflect contemporary standard practice and to isolate the effect of intracoronary prourokinase on outcomes.
The primary endpoint is the incidence of major adverse cardiovascular events (MACE) at 12 months after the intervention. MACE is defined as the composite occurrence of cardiovascular death, recurrent myocardial infarction, hospitalisation for unstable angina, unplanned repeat revascularisation, hospitalisation for heart failure, or non‑fatal stroke, with time‑to‑first event analysis.
Secondary endpoints focus on measures of myocardial reperfusion and injury, angina burden and cardiac function. These include:
These secondary outcomes aim to capture both mechanistic effects on reperfusion and clinical impacts on symptoms and function.
A key safety objective is to evaluate whether intracoronary prourokinase reduces MACE without increasing the incidence of major bleeding events. The study explicitly tracks major bleeding as a critical safety endpoint.
The trial will be conducted in accordance with the Declaration of Helsinki and applicable ethical guidelines. The study protocol received approval from the Medical Research Ethics Committee of Sun Yat‑sen Memorial Hospital of Sun Yat‑sen University (Approval No: SYSKY‑2024‑735‑04).
The primary analysis assesses the incidence of the composite MACE endpoint at 12 months, using time‑to‑first event methods. Secondary analyses evaluate reperfusion measures, infarct severity, angina class, cardiac function and short‑term events. Specific statistical assumptions, sample size calculations, randomisation stratification and interim analysis plans were included in the full protocol; those procedural details were not reported in the summary available here.
Patients will be followed for clinical events and predefined assessments through at least 12 months post‑PCI to capture the primary outcome and secondary endpoints.
Investigators plan to disseminate study results through peer‑reviewed journals, presentations at international conferences and stakeholder outreach targeted to clinicians, policymakers and patients. Digital platforms will be used to accelerate knowledge translation and support potential clinical implementation if results are favorable.
The trial is registered with the Chinese Clinical Trial Registry: ChiCTR2500103336.