The RECOVER IV Trial

Study Overview
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Brief Summary
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The purpose of this study is to assess whether hemodynamic support with an Impella-based treatment strategy initiated prior to percutaneous coronary intervention (PCI) in patients with ST-Segment Elevation Myocardial Infarction (STEMI)-Cardiogenic Shock (CS) improves survival and functional outcomes compared to a non-Impella-based treatment strategy.

Detailed Description
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To demonstrate that hemodynamic support with an Impella-based treatment strategy initiated prior to PCI, when compared with a non-Impella-based standard of care treatment strategy reduces all-cause mortality at 30 days in patients with STEMI-CS.

Official Title
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Early Impella® Support in Patients With ST-Segment Elevation Myocardial Infarction Complicated by Cardiogenic Shock: The RECOVER IV Trial

Conditions
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ST-segment Elevation Myocardial Infarction (STEMI), Cardiogenic Shock

Intervention / Treatment
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* Device: Impella CP®
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cardiogenic shock with onset ≤12 hours after STEMI and prior to index PCI, as defined by having both the following: Persistent SBP <90 mmHg for ≥30 minutes despite fluid resuscitation or pressors/inotropes required to maintain SBP ≥90 mmHg and Signs of impaired organ perfusion (cool extremities and/or altered mental status) One of the following must be present on a standard 12-lead electrocardiogram (ECG): ST-segment elevation (≥2 mm elevation of ST-segments in ≥2 contiguous leads without left bundle branch block) or Anterior (V1-V4) ST-segment depression ≥2 mm in ≥2 contiguous leads consistent with a possible posterior infarction AND coronary angiogram prior to randomization showing acute total or subtotal occlusion of the proximal circumflex artery or aVR ST-segment elevation ≥2 mm without anterior ST-segment elevation AND coronary angiogram prior to randomization confirming left main culprit lesion NOTE: Patients with isolated RV infarction are excluded from this Protocol. If a patient qualifies with cardiogenic shock with only inferior ST-segment elevation, pre-randomization assessment of LV function must be obtained with either point of care echocardiography or contrast left ventriculography to demonstrate a LVEF ≤40% for the patient to be eligible for randomization. Intended emergent PCI to treat the STEMI Subject is able to and agrees to provide written informed consent. If the subject is unable to be consented because of their extreme illness and a legally authorized representative (LAR) is present, the LAR must agree and provide written informed consent. If the subject is unable to provide consent because of their extreme illness and an LAR is not present, the patient may be randomized under Exception from Informed Consent (EFIC) Guidance Exclusion Criteria: High suspicion for isolated right ventricular infarct confirmed with ECG lead V4R Cardiogenic shock with either of the following: High-grade atrioventricular block (heart rate (HR) <50 bpm) NOTE: If patient is paced, via temporary or permanent pacemaker, and still in shock, they are still eligible Isolated narrow complex supraventricular tachycardia with ventricular response >170 bpm or ventricular tachyarrhythmia with ventricular response >150 bpm Known mechanical complications of acute myocardial infarction (AMI) that may cause cardiogenic shock such as free wall rupture, cardiac tamponade, ventricular septal defect or papillary muscle rupture with acute mitral regurgitation Left ventricular function (LVEF >40%) on echocardiography or LV-gram (if performed) indicating shock due to another cause (e.g., RV infarction as the principal cause of shock, hypovolemia, sepsis or high cardiac output shock) Severe bilateral peripheral arterial disease precluding femoral Impella CP insertion (femoral angiogram required) NOTE: Impella insertion via a non-femoral arterial route is not permitted in this Protocol. IABP, Impella or other mechanical circulatory support already in place for present indication (pre-randomization) Known end-stage renal disease, receiving dialysis Severe aortic stenosis, or moderate or worse aortic regurgitation or prior self-expanding transcatheter aortic valve replacement (TAVR), or surgically placed mechanical valve, if known Acute or chronic aortic dissection, if known Large or mobile LV thrombus, if known Prior PCI for the present infarction Prior PCI or coronary artery bypass graft (CABG) within 1 year, if known Ongoing cardiopulmonary resuscitation (CPR) Not obeying verbal commands after preadmission or in-hospital cardiac arrest NOTE: (i) A positive and appropriate response to commands must be repeatable on at least two (2) instances to rule out reflex response to voice (ii) Intubated subjects may be enrolled if: They did not have a cardiac arrest and were following verbal commands prior to intubation or They are clearly following verbal commands after intubation Prior stroke with permanent, significant neurological defect Prior intracranial hemorrhage or known intracerebral mass, aneurysm or fistula Acute or suspected stroke prior to randomization Active infection requiring oral or intravenous antibiotics Prior heparin-induced thrombocytopenia, if known Other severe, concomitant disease with limited life expectancy <1 year (other than cardiogenic shock) Pregnancy, known or suspected Participation in the active treatment or follow-up phase of another clinical study of an investigational drug or device that has not reached its primary endpoint or any cardiogenic shock trial other than a registry If known, subject has previously been symptomatic with or hospitalized for COVID-19 unless he/she has been discharged (if hospitalized) and asymptomatic for ≥4 weeks and has returned to his/her prior baseline (pre-COVID) clinical condition Subject has other medical, social or psychological conditions that, in the opinion of the Investigator, compromises the subject's ability to comply with study procedures (e.g., dementia, severe alcohol or substance abuse) Patient belongs to a vulnerable population [Vulnerable patient populations may include individuals with mental disability, persons in nursing homes, impoverished persons, homeless persons, nomads, refugees and those permanently incapable of giving informed consent. Vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces and persons kept in detention] Patient is wearing a bracelet or other item indicating their wishes to decline participation in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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, multicenter, randomized, controlled, open-label two-arm trial with an adaptive design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Arm<br>Subjects randomized to the Control Arm will be treated based on recommendations for cardiogenic shock in the contemporary AHA/ACC/SCAI and ESC Practice Guidelines for STEMI and Heart Failure Management and local standard of care. | Other: Standard of Care<br>* This may include inotropes and/or vasopressors. An IABP may or may not be used according to local practice and the specific condition of each individual patient. If an IABP is used, it may be placed prior to or after PCI, and its timing of explant is left to the discretion of the Investigator.<br>|
| Experimental: Treatment Arm<br>Subjects randomized to the Treatment Arm will receive hemodynamic support using an Impella-based treatment strategy initiated prior to percutaneous coronary intervention (PCI). | Device: Impella CP®<br>* Subjects randomized to the Treatment Arm will undergo Impella CP placement prior to PCI. Right heart catheterization will be performed prior to or immediately after PCI. Use of IABP will not be allowed in the Treatment Arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-Cause Mortality |  | 30 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) |  | 30 Days | 
| Days Alive Out-of-Hospital |  | 6 Months | 
| Mean Change in Health-Related Quality of Life, as measured by Kansas City Cardiomyopathy Questionnaire |  | 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular Diseases, Myocardial Infarction, Heart Failure, Exception From Informed Consent (EFIC), Cardiogenic Shock