Cardiogenic Shock, ST-segment Elevation Myocardial Infarction (STEMI)
Conditions
Keywords
Cardiovascular Diseases, Myocardial Infarction, Heart Failure, Exception From Informed Consent (EFIC), Cardiogenic Shock
Brief summary
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
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.
Interventions
DEVICEImpella CP®
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.
OTHERStandard of Care
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.
Sponsors
Abiomed Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, multicenter, randomized, controlled, open-label two-arm trial with an adaptive design
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Cardiogenic shock with onset ≤12 hours after STEMI and prior to index PCI, as defined by having both the following: 1. Persistent SBP \<90 mmHg for ≥30 minutes despite fluid resuscitation or pressors/inotropes required to maintain SBP ≥90 mmHg and 2. Signs of impaired organ perfusion (cool extremities and/or altered mental status) 2. One of the following must be present on a standard 12-lead electrocardiogram (ECG): 1. ST-segment elevation (≥2 mm elevation of ST-segments in ≥2 contiguous leads without left bundle branch block) or 2. 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 3. 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. 3. Intended emergent PCI to treat the STEMI 4. 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
1. High suspicion for isolated right ventricular infarct confirmed with ECG lead V4R 2. Cardiogenic shock with either of the following: 1. 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 2. Isolated narrow complex supraventricular tachycardia with ventricular response \>170 bpm or ventricular tachyarrhythmia with ventricular response \>150 bpm 3. 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 4. 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) 5. 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. 6. IABP, Impella or other mechanical circulatory support already in place for present indication (pre-randomization) 7. Known end-stage renal disease, receiving dialysis 8. 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 9. Acute or chronic aortic dissection, if known 10. Large or mobile LV thrombus, if known 11. Prior PCI for the present infarction 12. Prior PCI or coronary artery bypass graft (CABG) within 1 year, if known 13. Ongoing cardiopulmonary resuscitation (CPR) 14. 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: 1. They did not have a cardiac arrest and were following verbal commands prior to intubation or 2. They are clearly following verbal commands after intubation 15. Prior stroke with permanent, significant neurological defect 16. Prior intracranial hemorrhage or known intracerebral mass, aneurysm or fistula 17. Acute or suspected stroke prior to randomization 18. Active infection requiring oral or intravenous antibiotics 19. Prior heparin-induced thrombocytopenia, if known 20. Other severe, concomitant disease with limited life expectancy \<1 year (other than cardiogenic shock) 21. Pregnancy, known or suspected 22. 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 23. 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 24. 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) 25. Patient belongs to a vulnerable population \[Vulnerable patient populations may include individuals with mental disability, persons in nursing homes, impoverished persons, homeless persons, nomads, refugees and those permanently incapable of giving informed consent. Vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces and persons kept in detention\] 26. Patient is wearing a bracelet or other item indicating their wishes to decline participation in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| All-Cause Mortality | 30 Days |
Secondary
| Measure | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Health-Related Quality of Life, as measured by Rose Dyspnea Score | 30 Days Post-Discharge, 6 Months, 1 Year | — |
| Mean Change in Health-Related Quality of Life, as measured by EQ-5D-5L | 30 Days Post-Discharge, 6 Months, 1 Year | — |
| Left Ventricular Ejection Fraction (LVEF) | 30 Days, 6 Months | — |
| Estimated Glomerular Filtration Rate (eGFR) | At hemodynamic stability when the subject is no longer hospitalized, 30 Days, 6 Months, 1 Year | — |
| Number of Participants with need for In-Hospital Hemodialysis or Continuous Renal Replacement Therapy (CRRT) | At hemodynamic stability when the subject is no longer hospitalized | — |
| Number of Participants with need for Dialysis Post-Index Hospitalization | 30 Days, 6 Months, 1 Year | — |
| Number of Participants with any Dialysis | 30 Days, 6 Months, 1 Year | — |
| All-Cause Hospitalizations | 30 Days, 6 Months, 1 Year | — |
| Cardiovascular Hospitalizations | 30 Days, 6 Months, 1 Year | — |
| Heart Failure Hospitalizations | 30 Days, 6 Months, 1 Year | — |
| Number of Participants with new Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT) Implant | At hemodynamic stability when the subject is no longer hospitalized, 30 Days, 6 Months, 1 Year | — |
| Number of Participants with Left Ventricular Assist Device (LVAD) or Heart Transplant (including United Network for Organ Sharing (UNOS) 1/2 listing) | At hemodynamic stability when the subject is no longer hospitalized, 30 Days, 6 Months, 1 Year | — |
| All-Cause Mortality | At hemodynamic stability and when the subject is no longer hospitalized, 6 Months, 1 Year | — |
| Acute Kidney Injury (AKI) | within 7 Days Post-Percutaneous Coronary Intervention (PCI) | — |
| Disability Assessed using the Modified Rankin Scale | At hemodynamic stability when the subject is no longer hospitalized, 30 Days, 6 Months, 1 Year | — |
| 30-day survival with mRS score ≤3 | 30 day | — |
| Number of Participants with Neurologic Academic Research Consortium (NeuroARC) Type 1 Stroke | At hemodynamic stability when the subject is no longer hospitalized | — |
| Major Bleeding | Shock Academic Research Consortium (SHARC) Types 3-5, At hemodynamic stability when the subject is no longer hospitalized | — |
| Major Vascular Complications | SHARC Definition, At hemodynamic stability when the subject is no longer hospitalized | — |
| Major Hemolysis | At hemodynamic stability when the subject is no longer hospitalized | — |
| Major Cath Lab Complications | All adverse events will be recorded and documented through 1 year follow up or study completion | Intubation; new bradyarrhythmia requiring a temporary pacemaker; ventricular arrhythmias requiring cardioversion or defibrillation; persistent severe hypotension or heart failure requiring escalation beyond the randomized study devices (Impella CP in the Treatment Arm and intra-aortic balloon pump (IABP) in the Control Arm). |
| All Stroke | At hemodynamic stability when the subject is no longer hospitalized | — |
| Minor Bleeding | At hemodynamic stability when the subject is no longer hospitalized | — |
| Minor Vascular Complications | At hemodynamic stability when the subject is no longer hospitalized | — |
| Minor Hemolysis | At hemodynamic stability when the subject is no longer hospitalized | — |
| Repeat Target Vessel Revascularization (TVR) | 30 Days, 6 Months, 1 Year | — |
| MACCE | At hemodynamic stability when the subject is no longer hospitalized, 6 Months, 1 Year | — |
| Days Alive Out-of-Hospital | 30 Days, 6 Months | — |
| Mean Change in Health-Related Quality of Life, as measured by Kansas City Cardiomyopathy Questionnaire | 30 Days Post-Discharge, 6 Months | — |
Countries
Denmark, Germany, Switzerland, United States
Outcome results
None listed