Revascularization Strategy of Multivessel Disease for Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock Undergoing Veno-arterial Extracorporeal Membrane Oxygenator

Study Overview
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Brief Summary
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This study is a prospective, open-label, two-arm, randomized multicenter trial to identify whether immediate multi-vessel PCI would be better in clinical outcomes compared with culprit lesion-only PCI for AMI and multi-vessel disease with an advanced form of CS patients who require veno-arterial extracorporeal membrane oxygenator (VA-ECMO).

Detailed Description
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Cardiogenic shock (CS) is a fatal complication of acute myocardial infarction (AMI). Until now, in this setting, it has been well-known that early revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) was associated with improved clinical outcomes although the rate of mortality remains still high in the mechanical circulatory support (MCS) era. In real-world practice, since clinically significant non-infarct related artery (non-IRA) stenosis or occlusion in addition to an IRA can be found in 70% to 80% of patients with AMI complicated by CS, the decision of revascularization strategy is a crucial issue to improve clinical outcomes in CS patients with multivessel disease. The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) and the 2017 European Society of Cardiology (ESC) guidelines recommend considering PCI of severe stenosis in non-IRA during a primary procedure to improve overall myocardial perfusion and hemodynamic stability for patients with AMI and CS. However, the CULPRIT-SHOCK trial, which is the largest randomized trial in CS, demonstrated the 30-day risk of a composite of death or severe renal failure leading to renal-replacement therapy was higher in the immediate multi-vessel PCI than in the culprit lesion-only PCI group. In this regard, the recently updated guidelines do not recommend the routine non-IRA revascularization during primary PCI and it should be considered in selected cases in which there is a very severe flow-limiting non-IRA stenosis irrigating a large myocardial area. Nevertheless, there is still some unsolved issue regarding the role of non-IRA revascularization in AMI patients with CS. Majority of enrolled patients in the CULPRIT-SHOCK trial might have a mild form of CS (median systolic blood pressure of 100) and few patients received MCS devices (28.3% of study population). Furthermore, the mortality benefits of culprit-only PCI were attenuated at 1-year follow-up with an increased risk of repeat revascularization and hospitalization for heart failure. In contrast to the CULPRIT-SHOCK trial, the recent large United State registry from National Cardiovascular Data Registry demonstrated that the benefits of multi-vessel PCI in patients with non-ST-segment elevation MI and CS was more pronounced in those requiring MCS. In addition, recent data from the Korea Acute Myocardial Infarction National Health Registry showed that multivessel PCI was associated with a lower risk of all-cause death than culprit-only PCI, suggesting possible benefit of nonculprit lesion revascularization during the index hospitalization on long-term clinical outcomes. Therefore, the current randomized trial sought to identify whether immediate multi-vessel PCI would be better in clinical outcomes compared with culprit lesion-only PCI for AMI and multi-vessel disease with advanced form of CS patients who requiring veno-arterial extracorporeal membrane oxygenator (VA-ECMO).

Official Title
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REvaSCUlarization StratEgy of Multivessel Coronary Artery Disease for Patients With Acute Myocardial Infarction Complicated by Cardiogenic SHOCK Undergoing Veno-arterial Extracorporeal Membrane Oxygenator: Randomized-Controlled Trial (RESCUE-SHOCK)

Conditions
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Cardiogenic Shock, Acute Myocardial Infarction, Multi Vessel Coronary Artery Disease, Extracorporeal Membrane Oxygenation

Intervention / Treatment
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* Procedure: Culprit lesion only PCI
* Procedure: Immediate multi-vessel PCI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be at least 19 years of age Patients presented with AMI (ST-segment elevation MI [STEMI] or non-ST-segment elevation MI [NSTEMI]) complicated by CS (SCAI Shock classification C, D or E) who requiring VA-ECMO. Target lesions amenable for planned primary PCI by operators' decision Patients with multi-vessel disease Exclusion Criteria: Other causes of shock (hypovolemia, sepsis, obstructive shock). Shock due to mechanical complication to MI (rupture of papillary muscle, the ventricular septum, or free wall). Unwitnessed out of hospital cardiac arrest with persistent Glasgow coma scale <8 after the return of spontaneous circulation. Patients with single-vessel disease (Patients with single-vessel disease will be enrolled in the RESCUE-SHOCK registry) Onset of shock >24 hours. Known heparin intolerance. Other severe concomitant disease with limited life expectancy < 6 months Pregnancy or breast feeding Do not resuscitate wish

Ages Eligible for Study
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Minimum Age: 19 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
Interventional Model Description: Prospective, open-label, two-arm, randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Culprit-lesion only PCI arm<br>Patients will receive culprit-lesion only PCI. | Procedure: Culprit lesion only PCI<br>* Randomization will be done after coronary angiography before or during primary PCI for IRA. Patients will be randomized to either immediate multi-vesesl PCI group or culprit-lesion only PCI group with 1:1 ratio. This group will be taken culprit-lesion only PCI during primary PCI.<br>|
| Experimental: Immediate multi-vesesl PCI arm<br>Patients will receive immediate multi-vessel PCI. | Procedure: Immediate multi-vessel PCI<br>* Randomization will be done after coronary angiography before or during primary PCI for IRA. Patients will be randomized to either immediate multi-vesesl PCI group or culprit-lesion only PCI group with 1:1 ratio. This group will be taken immediate multi-vesesl PCI during primary PCI.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of all-cause mortality or advanced heart failure requiring cardiac replacement therapy | all-cause mortality or requiring left ventricular assisted device (LVAD) insertion or heart transplantation) | 90 days after primary PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of In-hospital mortality | Death by any cause in hospital | Up to 30 days | 
| Rates of In-hospital cardiac mortality | Death by cardiac cause in hospital | Up to 30 days | 
| Rates of VA-ECMO weaning success | Successful weaning of VA-ECMO was defined as successful removal of VA-ECMO and not requiring further mechanical support because of recurring cardiogenic shock over the following 48 hours. | Up to 30 days | 
| Time to VA-ECMO weaning | Time from VA-ECMO insertion to VA-ECMO weaning | Up to 30 days | 
| Rates of critical limb ischemia after successful VA-ECMO weaning | Critical limb ischemia is defined as limb pain that occurs at rest, or impending limb loss that is caused by severe compromise of blood flow to the affected extremity. (Rutherford classification 4, 5, or 6) | Up to 30 days | 
| Cerebral Performance Category (CPC) 3-5 at discharge | Neurologic performance scale at discharge | Up to 30 days | 
| Length of intensive-care unit (ICU) stay | ICU stay day | Up to 30 days | 
| Total procedural time | Procedural time (minutes) | Immediate after the index procedure | 
| Total amount of contrast use | Contrast use (cc) | Immediate after the index procedure | 
| Rates of all-cause mortality | Death by any cause | 90 Days and 12 months after primary PCI | 
| Rates of cardiac mortality | Death by cardiac cause | 90 Days and 12 months after primary PCI | 
| Requirement of cardiac replacement therapy | LVAD insertion or heart transplantation | 90 Days and 12 months after primary PCI | 
| Requirement of renal replacement therapy | Continuous renal replacement therapy, hemodialysis, or peritoneal dialysis | 90 Days and 12 months after primary PCI | 
| Rates of myocardial infarction (MI) | spontaneous MI during follow-up | 90 Days and 12 months after primary PCI | 
| Rates of MI related to culprit vessel | MI related to culprit vessel during follow-up | 90 Days and 12 months after primary PCI | 
| Rates of MI related to non-culprit vessel | MI related to non-culprit vessel during follow-up | 90 Days and 12 months after primary PCI | 
| Rates of stent thrombosis | Academic Research Consortium (ARC)-defined definite or probable stent thrombosis | 90 Days and 12 months after primary PCI | 
| Rates of Re-hospitalization due to heart failure | Re-hospitalization due to heart failure during follow-up | 90 Days and 12 months after primary PCI | 
| Rates of Re-hospitalization due to any cause | Re-hospitalization due to any cause during follow-up | 90 Days and 12 months after primary PCI | 
| Rates of target-lesion revascularization (TLR) | TLR during follow-up | 90 Days and 12 months after primary PCI | 
| Rates of target-vessel revascularization (TVR) | TVR during follow-up | 90 Days and 12 months after primary PCI | 
| Rates of repeat revascularization | Repeat revascularization during follow-up | 90 Days and 12 months after primary PCI | 
| Rates of cerebrovascular accident | Cerebrovascular accident during follow-up | 90 Days and 12 months after primary PCI | 
| Rates of bleeding | Bleeding ARC [BARC] type 2, 3, or 5 | 90 Days and 12 months after primary PCI | 
| Rates of major bleeding | (BARC type 3 or 5 | 90 Days and 12 months after primary PCI |