Cardiogenic Shock, Heart Failure, Reduced Ejection Fraction Heart Failure
Conditions
Keywords
Impella 5.5, Heart Failure Cardiogenic Shock, Reduced Ejection Fraction Heart Failure, Mechanical Circulatory Support, Cardiovascular Disease, Heart Disease, Guideline Directed Medical Therapy
Brief summary
The study will evaluate the impact of a combined device-drug strategy with Impella 5.5 with best practices and optimized GDMT on heart recovery outcomes in patients with decompensated heart failure and cardiogenic shock.
Detailed description
This is a prospective, single arm, multi-center, post-market, on-label study. For patients presenting with cardiogenic shock in the setting of cardiomyopathy, including peripartum cardiomyopathy, or myocarditis (also known as decompensated heart failure complicated with cardiogenic shock, commonly referred to as heart failure-related cardiogenic shock, HF-CS, including both acute-on-chronic and de novo presentations) as a result of isolated left ventricular failure that is not responsive to optimal medical management and conventional treatment measures (including volume loading and use of pressors and inotropes, with or without IABP), an intentional device-supported strategy with Impella 5.5™ for optimization of guideline-directed medical therapy (GDMT) combined with best practices improves outcomes over standard of care.
Interventions
DEVICEImpella 5.5 SmartAssist
The intervention is Impella 5.5 with SmartAssist® support combined with protocolized guideline directed medical therapy (GDMT) and HF-CS best practices.
Sponsors
Abiomed Inc.
Johnson & Johnson
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 and \< 80 years 2. Subject or subject's legally authorized representative (LAR) has signed the Informed Consent Form 3. LVEF ≤ 40% 4. Subject is presenting with decompensated heart failure and meets at least two (2) of the following cardiogenic shock criteria: 1. Hypotension (sustained episode of systolic blood pressure ≤ 90 mmHg for at least 30 minutes or need for inotropic/vasoactive agents to maintain such blood pressure) 2. Hypoperfusion (physical sign(s) of organ hypoperfusion or serum lactate \>2 mmol/L) 3. Cardiac index (CI) \< 2.2 L/min/m2 determined to be secondary to cardiac dysfunction, in the absence of hypovolemia 4. Required support with an intra-aortic balloon pump (IABP) or Impella CP™ 5. Subject has inadequate heart failure GDMT based on the most recent outpatient prescription prior to index admission, defined as: 1. On 2 or less of the 4-Pillar HF Drug Classes (BB, MRA, SGLT2i, and RASi) 2. If on BB and RASi, at least one of the two medications is \< 50% of the maximal target dose
Exclusion criteria
1. Underlying unmodifiable conditions that limit initiation of GDMT prior to enrollment, including but not limited to: 1. Drug allergies or hypersensitivities\* to HF GDMT medications, unless alternative can be identified \*Drug allergy/hypersensitivity is an immune-mediated reaction to a medication. Adverse reactions must be a result of immune or inflammatory cell stimulations by the mеԁiсаtion. 2. Known bilateral renal artery stenosis 3. Type 1 diabetes 4. 2o or 3o AV block, unless pacemaker is in place 5. Angioedema, hereditary or idiopathic 6. Pregnancy, known or confirmed by a pregnancy test if of childbearing potential 2. ST-segment elevation or acute coronary syndrome (ACS) prior to enrollment 3. Septic shock, shock from non-cardiac origins, or mixed shock 4. SCAI Stage E cardiogenic shock per study definition (Appendix C) prior to enrollment 5. In cardiac arrest prior to enrollment 6. Prolonged use (or use with complication) of Intra-aortic balloon pump (IABP) or Impella CP™ prior to enrollment, meeting at least one of the following: 1. IABP use \>24 hours if placed at the enrolling site or \>48 hours if transferred on IABP 2. Impella CP™ use \>24 hours if placed at the enrolling site or \>48 hours if transferred on Impella CP™ 3. Experienced complication(s) from IABP including clinically significant vascular injury, limb ischemia, end organ damage, or bleeding requiring transfusion(s) per Investigator's discretion 4. Experienced complication(s) from Impella CP™ including clinically significant hemolysis, vascular injury, limb ischemia, end organ damage, or bleeding requiring transfusion(s) per Investigator's discretion 7. On mechanical circulatory support other than IABP or Impella CP™ (i.e. ECMO, etc) or on mechanical ventilation for non-procedural reasons prior to enrollment 8. Revascularization or cardiac surgery within 30-days prior to enrollment 9. Infiltrative/restrictive cardiomyopathy (sarcoidosis and amyloidosis), hypertrophic cardiomyopathy, constrictive pericarditis, pericardiac tamponade, or myocarditis requiring high-dose immunosuppression 10. Complex adult congenital heart disease 11. Primary severe valvular disease 12. Predominant RV dysfunction per Investigator's discretion 13. History of heart transplant or listed for heart transplant or planned for heart transplantation prior to enrollment 14. Planned to be implanted with a permanent VAD within 180-days of the index hospitalization date 15. Continuous outpatient inotropic support prior to the index hospitalization date 16. Planned to pursue palliative care or hospice, or life expectancy of less than 1 year due to non-cardiac illness at the time of index hospitalization date 17. Currently on dialysis, or has pre-existing end-stage chronic kidney disease (stage 4 and above), or has nephropathy of hereditary, infectious, or autoimmune origin 18. Pre-existing functional liver disease including liver cirrhosis, alcoholic hepatitis, metabolic dysfunction associated steatohepatitis (MASH), or genetic liver disease 19. Pre-existing pulmonary disease with oxygen dependency 20. History of stroke or intracranial hemorrhage ≤ 90 days prior to the index hospitalization date, or a history of cerebrovascular disease with significant (\> 80%) uncorrected carotid stenosis, or any permanent neurological deficit with modified Rankin Scale (mRS) \>2 21. Any contraindication that precludes placing an Impella 5.5™, including but not limited to: 1. Aortic valve stenosis/calcification with orifice area ≤ 0.6cm2 or aortic insufficiency of any grade greater than mild on pre-procedure echocardiography 2. Presence of mechanical aortic valve or heart constrictive device 3. Mural thrombus in the left ventricle 4. Severe arterial disease precluding placement of Impella 5. Presence of atrial or ventricular septal defect 6. Left ventricular rupture 7. Cardiac tamponade 8. Combined cardiorespiratory failure 22. Infection of the planned procedural access site or systemic active infection including sepsis and bacteremia 23. Intolerance to anticoagulant or antiplatelet therapies, or will refuse blood transfusions 24. Subject has other medical, social or psychological problems that, in the opinion of the Investigator, compromises the subject's ability to give written informed consent and/or to comply with study procedures 25. Participation in the active treatment or follow-up phase of another clinical study of an investigational drug or device 26. Subject belongs to a vulnerable population, such as prisoners, pregnant women, handicapped, mentally disabled persons, or economically or educationally disadvantaged persons per 21CFR56.111(a)(3) and 111(b)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite of all-cause death, HF hospitalization, and heart replacement (heart transplantation or durable LVAD implantation) | Timeframe: 180-days post-enrollment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite of all-cause death and heart replacement | 90-days, 180-days, 1-year post-enrollment | — |
| Composite of all-cause death, HF hospitalization, and heart replacement | 90-days, 1-year post-enrollment | — |
| All-cause mortality | Hospital Discharge (within 24 hours) , 90-days, 180-days, 1-year post-enrollment | — |
| Cardiovascular mortality | Hospital Discharge (within 24 hours), 90-days, 180-days, 1-year post-enrollment | — |
| Worsening heart failure | 90-days, 180-days, 1-year post-enrollment | HF hospitalization or urgent HF visit |
| Composite of all-cause death and worsening heart failure | 90-days, 180-days, 1-year post-enrollment | — |
| Non-HF cardiovascular hospitalization | 90-days, 180-days, 1-year post-enrollment | — |
| All cardiovascular hospitalization | 90-days, 180-days, 1-year post-enrollment | — |
| Composite of all-cause death and all cardiovascular hospitalization | 90-days, 180-days, 1-year post-enrollment | — |
| Rate of major device-related adverse events | Hospital Discharge (within 24 hours), 30-days post-enrollment | The composite rate of any of the following device-related serious adverse events: 1. Major vascular access site complication 2. Major hemolysis 3. Bleeding, defined as MCS-ARC Type 3 or higher 4. Structural complication requiring repair 5. Stroke |
| Subjects achieving indicated GDMT treatment | Hospital Discharge(within 24 hours), 90-days, 180-days post-enrollment | Achieving any dose of all four classes |
| % of Subjects achieving optimized GDMT treatment | 90-days and 180-days post-enrollment | Achieving at least 50% of the target dose of all four classes |
| Modified Heart Failure Collaboratory (mHFC) score | Hospital Discharge(within 24 hours), 90-days, 180-days post-enrollment | Defined by HFC in 2022. Improvement from baseline |
| Rate of GDMT-Related Serious Adverse Events | Hospital Discharge (within 24 hours), 90-days, and 180-days post-enrollment | The composite rate of any of the following GDMT-related serious adverse events: 1. Recurrence or worsening shock; symptomatic hypotension requiring admission 2. Bradycardia requiring treatment 3. Hyperkalemia requiring intervention 4. Ketoacidosis requiring treatment 5. Need for new renal replacement therapy (RRT) |
| Quality of life assessed by EQ-5D | 180-days and 1-year post-discharge | improvement from baseline |
| 6-Minute Walk Test Distance | 180-days and 1-year post-discharge | improvement from baseline |
| Change in LVEF from baseline | 180-days post-discharge | — |
| Change in LVEDD from baseline | 180-days post-discharge | — |
| Change in NYHA HF Class from baseline | 180-days post-discharge | — |
| Change in HF biomarker | Hospital Discharge (within 24 hours), 30-days, and 90-days post-discharge | NT-proBNP from baseline |
Countries
United States
Contacts
CONTACTRoberta Chapman, MD, FACC, FACP, FHFSA
CONTACTStacie Hallaway
PRINCIPAL_INVESTIGATORAdam DeVore, MD, MHS
Duke University
PRINCIPAL_INVESTIGATORGavin Hickey, MD
University of Pittsburgh
PRINCIPAL_INVESTIGATORManreet Kanwar, MD
University of Chicago
Outcome results
None listed