The RECOVER IV Trial (RECOVER IV)

• ClinicalTrials.gov Identifier: NCT05506449
• Recruitment Status: Recruiting
• First Posted: August 18, 2022
• Last Update Posted: January 24, 2024
• Sponsor: Abiomed Inc.
• Information provided by (Responsible Party): Abiomed Inc.

Tracking Information

• First Submitted Date: August 15, 2022
• First Posted Date: August 18, 2022
• Last Update Posted Date: January 24, 2024
• Actual Study Start Date: October 28, 2023
• Estimated Primary Completion Date: April 30, 2026 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 16, 2022): All-Cause Mortality [ Time Frame: 30 Days ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 16, 2022)

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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 16, 2022)

• All-Cause Mortality [ Time Frame: At hemodynamic stability and when the subject is no longer hospitalized, 6 Months, 1 Year ]
• MACCE [ Time Frame: At hemodynamic stability when the subject is no longer hospitalized, 6 Months, 1 Year ]
• Days Alive Out-of-Hospital [ Time Frame: 30 Days, 6 Months ]
• Mean Change in Health-Related Quality of Life, as measured by Kansas City Cardiomyopathy Questionnaire [ Time Frame: 30 Days Post-Discharge, 6 Months ]
• Mean Change in Health-Related Quality of Life, as measured by Rose Dyspnea Score [ Time Frame: 30 Days Post-Discharge, 6 Months, 1 Year ]
• Mean Change in Health-Related Quality of Life, as measured by EQ-5D-5L [ Time Frame: 30 Days Post-Discharge, 6 Months, 1 Year ]
• Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 30 Days, 6 Months ]
• Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: 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) [ Time Frame: At hemodynamic stability when the subject is no longer hospitalized ]
• Number of Participants with need for Dialysis Post-Index Hospitalization [ Time Frame: 30 Days, 6 Months, 1 Year ]
• Number of Participants with any Dialysis [ Time Frame: 30 Days, 6 Months, 1 Year ]
• All-Cause Hospitalizations [ Time Frame: 30 Days, 6 Months, 1 Year ]
• Cardiovascular Hospitalizations [ Time Frame: 30 Days, 6 Months, 1 Year ]
• Heart Failure Hospitalizations [ Time Frame: 30 Days, 6 Months, 1 Year ]
• Number of Participants with new Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT) Implant [ Time Frame: 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) [ Time Frame: At hemodynamic stability when the subject is no longer hospitalized, 30 Days, 6 Months, 1 Year ]
• Repeat Target Vessel Revascularization (TVR) [ Time Frame: 30 Days, 6 Months, 1 Year ]
• Acute Kidney Injury (AKI) [ Time Frame: within 7 Days Post-Percutaneous Coronary Intervention (PCI) ]
• Disability Assessed using the Modified Rankin Scale [ Time Frame: At hemodynamic stability when the subject is no longer hospitalized, 30 Days, 6 Months, 1 Year ]
• 30-day survival with mRS score ≤3 [ Time Frame: 30 day ]
• Number of Participants with Neurologic Academic Research Consortium (NeuroARC) Type 1 Stroke [ Time Frame: At hemodynamic stability when the subject is no longer hospitalized ]
• Major Bleeding [ Time Frame: Shock Academic Research Consortium (SHARC) Types 3-5, At hemodynamic stability when the subject is no longer hospitalized ]
• Major Vascular Complications [ Time Frame: SHARC Definition, At hemodynamic stability when the subject is no longer hospitalized ]
• Major Hemolysis [ Time Frame: At hemodynamic stability when the subject is no longer hospitalized ]
• Major Cath Lab Complications [ Time Frame: 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 [ Time Frame: At hemodynamic stability when the subject is no longer hospitalized ]
• Minor Bleeding [ Time Frame: At hemodynamic stability when the subject is no longer hospitalized ]
• Minor Vascular Complications [ Time Frame: At hemodynamic stability when the subject is no longer hospitalized ]
• Minor Hemolysis [ Time Frame: At hemodynamic stability when the subject is no longer hospitalized ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Prospective, multicenter, randomized, controlled, open-label two-arm trial with an adaptive design

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• ST-segment Elevation Myocardial Infarction (STEMI)
• Cardiogenic Shock

Intervention

• Device: Impella 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.

• Other: Standard 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.

Study Arms

• Active Comparator: Control Arm
  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.
  Intervention: Other: Standard of Care
• Experimental: Treatment Arm
  Subjects randomized to the Treatment Arm will receive hemodynamic support using an Impella-based treatment strategy initiated prior to percutaneous coronary intervention (PCI).
  Intervention: Device: Impella CP®

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 16, 2022): 560
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 30, 2027
• Estimated Primary Completion Date: April 30, 2026 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sameera Dasari, PhD; 978-914-8882; sdasari@abiomed.com

• Listed Location Countries: Germany, United States

Administrative Information

• NCT Number: NCT05506449
• Other Study ID Numbers: ABMD-CIP-22-02
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Abiomed Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Abiomed Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Navin Kapur, MD; Tufts Medical Center
• Principal Investigator: William O'Neill, MD; Henry Ford Health System
• Study Chair: Gregg Stone, MD; Icahn School of Medicine at Mount Sinai

• PRS Account: Abiomed Inc.
• Verification Date: January 2024