NCT03753269

Early Intracoronary Administration of Fasudil in the Primary PCI of ST-segment-Elevation Myocardial Infarction

Efficacy of Early Intracoronary Administration of Fasudil Hydrochloride on Myocardial Perfusion in the Primary PCI of ST-elevation Myocardial Infarction: an Prospective, Randomized and Multicenter Trial

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 600 (estimated)
• Sponsor: RenJi Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The study aims to evaluate whether an early intracoronary administration of Fasudil Hydrochloride during primary PCI of STEMI can improve epicardial and myocardial perfusion as well as clinical outcomes.

Detailed description

Timely reperfusion therapy is the most effective treatment for acute STEMI patients. Primary PCI has been documented as the best method for restoration of epicardial blood flow. Nevertheless, recovery of epicardial blood flow does not necessarily equate to a sufficient reperfusion at myocardial level. Although epicardial TIMI 3 flow could be achieved in the majority of STEMI patients by contemporary PPCI, it has been well acknowledged that microvascular obstruction (MVO) is far more prevalent than the epicardial no-reflow phenomenon and has huge detrimental impact on clinical outcomes. Routine thrombus aspiration by special catheter during primary PCI has shown negative or even harmful results in clinical trials. Distal coronary protective devices are also ineffective to improve myocardial perfusion. On the contrary, peri-procedual administration of several medications has shown possibilities to reduce MVO. These medications are mostly anti-platelet agents such as GP IIb/IIIa receptor and microvascular dilators like adenosine, sodium nitroprusside and verapamil. Theoretically, intracoronary delivery of medications can be more effective and potentially decrease side effects. Empirical application of aforementioned agents seems to improve the epicardial flow in patients not achieving TIMI 3 flow after PCI. However, it is debatable whether early administration of intracoronary medication (meaning before PCI) may further reduce MVO assuming it could be better to reduce reperfusion injury. However, this has not been well investigated yet. Rho-associated protein kinase (Rho kinase) is expressed in many cells, including smooth muscle cells and vascular endothelial. Activation of Rho kinase leads to increased smooth muscle intracellular calcium and robust vasoconstriction. Fasudil hydrochloride is a rho-kinase inhibitor that severs clinically as a potent small vessel dilator, especially in the field of cerebral circulation. Meanwhile, It has been empirically used in individual STEMI cases and showed effectiveness in improving coronary flow for PCI therapy. This study aims to evaluate whether an early intracoronary administration of Fasudil Hydrochloride can improve myocardial perfusion and clinical outcomes for STEMI patients undergoing primary PCI. To ensure the complete delivery of agents within coronary, a special-designed targeted perfusion micro-catheter will be used for drug delivery. Patients in the control arm will be administrated by intracoronary saline. For the results, coronary angiography-based index of epical and myocardial perfusion will be analyzed. MVO will be determined by cardiac magnetic resonance imaging and quantified as the percentage of left ventricular myocardial mass (% LV). The rate of composite major adverse cardiac events (MACEs) at 30 days and 6 months since symptom onset will be the clinical outcomes.

Conditions

• ST Segment Elevation Myocardial Infarction

Interventions

Type	Name	Description
DRUG	Fasudil Hydrochloride	2.5mg fasudil hydrochloride (diulted to 15ml by 0.9% saline )will be delivered by targeted perfusion micro-catheter into culprit vessel right after the first wire passage
DRUG	Placebo saline	15ml 0.9% saline will be delivered by targeted perfusion micro-catheter into culprit vessel right after the first wire passage

Timeline

• Start date: 2019-07-01
• Primary completion: 2022-06-30
• Completion: 2022-12-30
• First posted: 2018-11-26
• Last updated: 2018-11-26