IMPROVE-STEMI: pPCI Plus Low-dose r-SK in STEMI

Background:

Acute ST-segment elevation myocardial infarction (STEMI) is a critical condition caused by acute thrombotic occlusion of coronary arteries. Although primary percutaneous coronary intervention (pPCI) is the standard treatment, high thrombus burden often leads to slow flow or no-reflow phenomenon, affecting patient prognosis. Intracoronary thrombolysis has emerged as an adjunctive strategy to improve microvascular perfusion. Recombinant streptokinase, a genetically engineered thrombolytic agent with reduced antigenicity, has shown potential in improving myocardial reperfusion. This study aims to systematically evaluate the efficacy and safety of pPCI combined with intracoronary low-dose recombinant streptokinase in STEMI patients, and to provide high-level evidence for clinical translation.

Study Design:

This study consists of two parts:

Core Study: A multicenter, prospective, open-label, pragmatic, randomized controlled trial. A total of 300 patients will be randomized 1:1 to the experimental group (pPCI + intracoronary recombinant streptokinase, n=150) or the control group (pPCI alone, n=150).

Extended Study: A multicenter, prospective, open-label, observational study. A total of 3,000 patients will be enrolled to receive pPCI + intracoronary recombinant streptokinase.

Intervention:

In the experimental group, patients will receive an intracoronary injection of 300,000 IU recombinant streptokinase dissolved in 5% glucose 5mL, administered distal to, within, and proximal to the thrombus via a microcatheter or perforated balloon after guidewire crossing. The control group will receive standard pPCI only. Concomitant use of other thrombolytic agents (e.g., urokinase, alteplase, reteplase, tenecteplase, recombinant human prourokinase) is prohibited during the observation period.

Outcomes:

The primary outcome is the coronary angiography-derived index of microcirculatory resistance (caIMR) immediately after PCI. Secondary outcomes include:

Incidence of MACE (all-cause death, recurrent myocardial infarction, target vessel revascularization, heart failure rehospitalization, and stroke) at 1 year.

TIMI flow grade and corrected TIMI frame count (CTFC) immediately after PCI.

Coronary angiography-derived fractional flow reserve (caFFR).

ST-segment resolution >50% and >70% at 1 hour post-PCI.

Myocardial infarct size, myocardial salvage index (MSI), left ventricular ejection fraction (LVEF), microvascular obstruction, and intramyocardial hemorrhage (assessed by cardiac MRI at Day 5 ± 2 days).

Length of hospital stay.

Sample Size:

For the core study, assuming a mean caIMR of 28.19 ± 7.26 in the experimental group and 33.56 ± 8.47 in the control group, with a 1:1 ratio, α=0.05 (two-sided), and 90% power, 94 patients are required. Considering a 20% dropout rate, 118 patients are needed. To account for center effects and improve subgroup analysis power, the final sample size is set at 300 patients (150 per group). For the extended study, a single-arm target value method is used, with a planned enrollment of 3,000 patients to describe caIMR distribution and accumulate safety data in various subgroups.

Follow-up:

The observation period is divided into screening/baseline (Day -1 to 0), treatment (Day 0), and follow-up (Day 5 ± 2, Week 4 ± 7, Week 12 ± 7, Week 24 ± 7, and Week 52 ± 7). The primary analysis will use the Full Analysis Set (FAS) and Safety Set (SS). Statistical analysis will be performed using SAS 9.4.

Safety:

Safety endpoints include major and minor bleeding events (TIMI criteria) within 7 days, vital signs, blood routine, liver and kidney function, and the incidence of adverse events. The study has been approved by the Ethics Committee of the Affiliated Hospital of Xuzhou Medical University (Approval Number: XYFY2026-KL268-01).