Effect of Low-dose Intracoronary Reteplase on Myocardial Infarct Size During Primary Percutaneous Coronary Intervention

Study Overview
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Brief Summary
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OBJECTIVE: To determine whether a therapeutic strategy involving low-dose intracoronary fibrinolytic therapy with reteplase infused after coronary reperfusion will reduce the myocardial infarction size. DESIGN, SETTING, AND PARTICIPANTS: 306 patients presenting at 15 hospitals in China within 12 hours of acute ST-segment elevation myocardial infarction (STEMI) due to a proximal-mid-vessel occlusion of left anterior descending (LAD) coronary artery occlusion will be randomized in a 1:1:1 dose-ranging trial design. Patients will be followed up to 1 month. INTERVENTIONS: Participants will be randomly assigned to treatment with placebo (n = 102), reteplase 9mg (n = 102), or reteplase 18mg (n = 102) by manual infusion over 2 minutes after reperfusion of the infarct-related coronary artery and before stent implant. MAIN OUTCOMES AND MEASURES The primary outcomewas the myocardial infarct size (% left ventricular mass) demonstrated by contrast-enhanced cardiac magnetic resonance imaging (MRI) conducted from days 2 through 7 after enrollment.

Official Title
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Effect of Low-dose Intracoronary Reteplase During Primary Percutaneous Coronary Intervention on Myocardial Infarct Size in Patients With Acute Myocardial Infarction

Conditions
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Acute ST-segment Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: Normal Saline
* Drug: Reteplase Injection 9mg
* Drug: Reteplase Injection 18mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute STEMI with persistent ST-segment elevation or recent left bundle-branch block with a symptom onset to reperfusion time of 12 hours or less. Angiographic criteria included a proximal-mid coronary artery occlusion (TIMI coronary flow grade 0 or 1) or, impaired coronary flow (TIMI flow grade 2, slow but complete filling) in the presence of definite angiographic evidence of large thrombus (TIMI grade ≥2) in left anterior descending (LAD) coronary artery. Exclusion Criteria: Rescue PCI after thrombolytic therapy. Need for emergency coronary artery bypass grafting. Presence of cardiogenic shock. Life expectancy of < 6 months. Inability to provide informed consent. Contraindications for the use of thrombolysis, including active internal bleeding, history of intracranial haemorrhage or ischaemic stroke within 6 months, recent major surgery or trauma, severe uncontrolled hypertension, thrombocytopenia and severe liver or kidney failure.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>intracoronary infusion with saline | Drug: Normal Saline<br>* intracoronary infusion with normal saline<br>* Other names: intracoronary normal saline;|
| Experimental: reteplase 9mg<br>intracoronary infusion with reteplase 9mg | Drug: Reteplase Injection 9mg<br>* low-dose intracoronary fibrinolytic therapy with reteplase 9mg<br>* Other names: intracoronary reteplase 9mg;|
| Experimental: reteplase 18mg<br>intracoronary infusion with reteplase 18mg | Drug: Reteplase Injection 18mg<br>* low-dose intracoronary fibrinolytic therapy with reteplase 18mg<br>* Other names: intracoronary reteplase 18mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial infarct size | Myocardial infarct size (% left ventricular mass) demonstrated by contrast-enhanced cardiac magnetic resonance imaging (MRI) | from days 2 through 7 after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of microvascular obstruction | The amount of microvascular obstruction (% of left ventricular mass) demonstrated by late gadolinium-enhanced MRI | from days 2 through 7 after enrollment | 
| ST-segment resolution | The percentage ST-segment resolution on an electrocardiogram | 60 minutes after reperfusion | 
| CKMB level | CKMB area under the curve (AUC) | immediately before reperfusion (0 hours) and then again at 2 hours and at 24 hours | 
| Left ventricular ejection fraction | Left ventricular ejection fraction assessed by echocardiography | 1 and 30 days after PCI | 
| Incidence of major adverse cardiac events (MACE) | The composite of cardiac mortality, nonfatal myocardial reinfarction and target vessel revascularization | 30 days after PCI | 
| Myocardial Blush Grade | Angiographic measures of reperfusion. The score goes from 0 to 3, with 3 being normal and 0 being absence of myocardial blush | 0-1 hour at the end of PCI | 
| TIMI corrected frame count | Angiographic measures of reperfusion. Thrombolysis in myocardial infarction score with corrected frame count from angiogram to assess myocardial perfusion | 0-1 hour at the end of PCI | 
| TIMI flow grade | Angiographic measures of reperfusion. The score goes from 0 to 3, with 3 being normal and 0 being absence of coronary flow | 0-1 hour at the end of PCI |