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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute ST-segment Elevation Myocardial Infarction
• Intervention / Treatment: Drug: Normal Saline; Drug: Reteplase Injection 9mg; Drug: Reteplase Injection 18mg

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Department of Cardiology, Zhongshan Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ge Junbo
• Investigators: Principal Investigator: Junbo Ge, Department of Cardiology, Zhongshan Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: September 19, 2020
• First Submitted That Met QC Criteria: September 26, 2020
• First Posted (Actual): October 1, 2020

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Reteplase
• Other Study ID Numbers: RECOVERII

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No