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

Phase 3

Terminated

• Conditions: Acute ST-segment Elevation Myocardial Infarction
• Interventions: Drug: Normal Saline; Drug: Reteplase Injection 9mg; Drug: Reteplase Injection 18mg

• Registration Number: NCT04571580
• Lead Sponsor: Ge Junbo

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-19
• Study First Submitted QC: 2020-09-26
• Study First Posted: 2020-10-01
• Study Start: 2021-07-01
• Primary Completion: 2023-01-31
• Study Completion: 2023-01-31
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-13
• Last Update Posted: 2023-09-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 36

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Normal Saline	intracoronary infusion with saline
reteplase 9mg	Reteplase Injection 9mg	intracoronary infusion with reteplase 9mg
reteplase 18mg	Reteplase Injection 18mg	intracoronary infusion with reteplase 18mg

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
TIMI flow grade	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
Amount of microvascular obstruction	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	60 minutes after reperfusion	The percentage ST-segment resolution on an electrocardiogram
CKMB level	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	1 and 30 days after PCI	Left ventricular ejection fraction assessed by echocardiography
Incidence of major adverse cardiac events (MACE)	30 days after PCI	The composite of cardiac mortality, nonfatal myocardial reinfarction and target vessel revascularization
Myocardial Blush Grade	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	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

Trial Locations

Locations (1)

Department of Cardiology, Zhongshan Hospital, Fudan University; 🇨🇳 Shanghai, Shanghai, China