Clinical trial NCT05506449: The RECOVER IV Trial
Official title: Early Impella® Support in Patients With ST-Segment Elevation Myocardial Infarction Complicated by Cardiogenic Shock: The RECOVER IV Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: ST-segment Elevation Myocardial Infarction (STEMI)
Cardiogenic Shock
Keywords: Cardiovascular Diseases
Myocardial Infarction
Heart Failure
Exception From Informed Consent (EFIC)
Cardiogenic Shock
Lead sponsor: Abiomed Inc.
Sponsor class: INDUSTRY
First posted: 2022-08-18
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, multicenter, randomized, controlled, open-label two-arm trial with an adaptive design
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: All-Cause Mortality
timeFrame: 30 Days
Secondary outcomes:
measure: Major Adverse Cardiovascular and Cerebrovascular Events (MACCE)
timeFrame: 30 Days
measure: Days Alive Out-of-Hospital
timeFrame: 6 Months
measure: Mean Change in Health-Related Quality of Life, as measured by Kansas City Cardiomyopathy Questionnaire
timeFrame: 1 Year
Other outcomes:
measure: All-Cause Mortality
timeFrame: At hemodynamic stability and when the subject is no longer hospitalized, 6 Months, 1 Year
measure: MACCE
timeFrame: At hemodynamic stability when the subject is no longer hospitalized, 6 Months, 1 Year
measure: Days Alive Out-of-Hospital
timeFrame: 30 Days, 6 Months
measure: Mean Change in Health-Related Quality of Life, as measured by Kansas City Cardiomyopathy Questionnaire
timeFrame: 30 Days Post-Discharge, 6 Months
measure: Mean Change in Health-Related Quality of Life, as measured by Rose Dyspnea Score
timeFrame: 30 Days Post-Discharge, 6 Months, 1 Year
measure: Mean Change in Health-Related Quality of Life, as measured by EQ-5D-5L
timeFrame: 30 Days Post-Discharge, 6 Months, 1 Year
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 30 Days, 6 Months
measure: Estimated Glomerular Filtration Rate (eGFR)
timeFrame: At hemodynamic stability when the subject is no longer hospitalized, 30 Days, 6 Months, 1 Year
measure: Number of Participants with need for In-Hospital Hemodialysis or Continuous Renal Replacement Therapy (CRRT)
timeFrame: At hemodynamic stability when the subject is no longer hospitalized
measure: Number of Participants with need for Dialysis Post-Index Hospitalization
timeFrame: 30 Days, 6 Months, 1 Year
measure: Number of Participants with any Dialysis
timeFrame: 30 Days, 6 Months, 1 Year
measure: All-Cause Hospitalizations
timeFrame: 30 Days, 6 Months, 1 Year
measure: Cardiovascular Hospitalizations
timeFrame: 30 Days, 6 Months, 1 Year
measure: Heart Failure Hospitalizations
timeFrame: 30 Days, 6 Months, 1 Year
measure: Number of Participants with new Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT) Implant
timeFrame: At hemodynamic stability when the subject is no longer hospitalized, 30 Days, 6 Months, 1 Year
measure: Number of Participants with Left Ventricular Assist Device (LVAD) or Heart Transplant (including United Network for Organ Sharing (UNOS) 1/2 listing)
timeFrame: At hemodynamic stability when the subject is no longer hospitalized, 30 Days, 6 Months, 1 Year
measure: Repeat Target Vessel Revascularization (TVR)
timeFrame: 30 Days, 6 Months, 1 Year
measure: Acute Kidney Injury (AKI)
timeFrame: within 7 Days Post-Percutaneous Coronary Intervention (PCI)
measure: Disability Assessed using the Modified Rankin Scale
timeFrame: At hemodynamic stability when the subject is no longer hospitalized, 30 Days, 6 Months, 1 Year
measure: 30-day survival with mRS score ≤3
timeFrame: 30 day
measure: Number of Participants with Neurologic Academic Research Consortium (NeuroARC) Type 1 Stroke
timeFrame: At hemodynamic stability when the subject is no longer hospitalized
measure: Major Bleeding
timeFrame: Shock Academic Research Consortium (SHARC) Types 3-5, At hemodynamic stability when the subject is no longer hospitalized
measure: Major Vascular Complications
timeFrame: SHARC Definition, At hemodynamic stability when the subject is no longer hospitalized
measure: Major Hemolysis
timeFrame: At hemodynamic stability when the subject is no longer hospitalized
measure: Major Cath Lab Complications
timeFrame: All adverse events will be recorded and documented through 1 year follow up or study completion
measure: All Stroke
timeFrame: At hemodynamic stability when the subject is no longer hospitalized
measure: Minor Bleeding
timeFrame: At hemodynamic stability when the subject is no longer hospitalized
measure: Minor Vascular Complications
timeFrame: At hemodynamic stability when the subject is no longer hospitalized
measure: Minor Hemolysis
timeFrame: At hemodynamic stability when the subject is no longer hospitalized
Locations:
city: Albuquerque
country: United States
facility: New Mexico Heart Institute
state: New Mexico
city: Copenhagen
country: Denmark
facility: Rigshospitalet Copenhagen
city: Dresden
country: Germany
facility: Herzzentrum Dresden
state: Saxony
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig Holstein
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Brüder Trier
city: Bern
country: Switzerland
facility: Inselspital Bern
Study officials:
affiliation: Tufts Medical Center
name: Navin Kapur, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Henry Ford Health System
name: William O'Neill, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Gregg Stone, MD
role: STUDY_CHAIR
References: