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

Overview

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.

Full Title of Study: “Effect of Low-dose Intracoronary Reteplase During Primary Percutaneous Coronary Intervention on Myocardial Infarct Size in Patients With Acute Myocardial Infarction”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: January 31, 2023

Interventions

  • Drug: Normal Saline
    • intracoronary infusion with normal saline
  • Drug: Reteplase Injection 9mg
    • low-dose intracoronary fibrinolytic therapy with reteplase 9mg
  • Drug: Reteplase Injection 18mg
    • low-dose intracoronary fibrinolytic therapy with reteplase 18mg

Arms, Groups and Cohorts

  • Placebo Comparator: placebo
    • intracoronary infusion with saline
  • Experimental: reteplase 9mg
    • intracoronary infusion with reteplase 9mg
  • Experimental: reteplase 18mg
    • intracoronary infusion with reteplase 18mg

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

Inclusion Criteria

1. 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. 2. 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:

1. Rescue PCI after thrombolytic therapy. 2. Need for emergency coronary artery bypass grafting. 3. Presence of cardiogenic shock. 4. Life expectancy of < 6 months. 5. Inability to provide informed consent. 6. 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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Ge Junbo
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Ge Junbo, Director, Dept. of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China – Fudan University
  • Overall Official(s)
    • Junbo Ge, Principal Investigator, Department of Cardiology, Zhongshan Hospital

Citations Reporting on Results

Huang D, Ma Y, Wu H, Zhong X, Gao W, Zhou J, Qian J, Ge J. Impact of intracoronary reteplase during primary percutaneous coronary intervention on infarct size in large anterior myocardial infarction: rationale and design of the RECOVER II trial. Cardiovasc Diagn Ther. 2022 Jun;12(3):352-359. doi: 10.21037/cdt-21-756.

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