INitiation and Titration of Guideline Directed Medical TheRApy in HearT Failure Cardiogenic Shock With ImpElla 5.5 for Cardiac Recovery (INTeGRATE)

Initiation and Titration of Guideline Directed Medical Therapy in Heart Failure Cardiogenic Shock With Impella 5.5 for Cardiac Recovery: INTeGRATE

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure; Cardiogenic Shock; Reduced Ejection Fraction Heart Failure
• Intervention / Treatment: Device: Impella 5.5 SmartAssist

Detailed Description

This is a prospective, single arm, multi-center, post-market, on-label study. Patients presenting with heart failure cardiogenic shock (HF-CS), 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. The study objectives are to 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.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Roberta Chapman, MD, FACC, FACP, FHFSA; Phone Number: +1 978-882-8421; Email: rchapm11@its.jnj.com
• Study Contact Backup: Name: Stacie Hallaway; Phone Number: 839-216-3087; Email: shallawa@its.jnj.com

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
      • Contact: Courtney Nicholas, BS RN, CCRP, CVRN-BC; Phone Number: 813-844-4914; Email: courtneynicholas@tgh.org
      • Principal Investigator: Debbie Rinde-Hoffman, MD, FACC, FACP, FHFSA
  • Minnesota
    • Minneapolis, Minnesota, United States, 555407
      • Abbott Northwestern
      • Contact: Juilanne Feola; Phone Number: 612-863-6066; Email: julianne.feola@allina.com
      • Principal Investigator: Kasia Hryniewicz, MD
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers-Robert Wood Johnson Medical School
      • Contact: Manisha Bajpai, MD; Phone Number: 732-258-3649; Email: bajpaima@rwjms.rutgers.edu
      • Principal Investigator: Maya Guglin, MD, PhD
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Atrium Health
      • Contact: Haley Bonilla; Phone Number: 704-468-3193; Email: haley.bonilla@atriumhealth.org
      • Principal Investigator: Priyesh Patel, M.D.
    • Durham, North Carolina, United States, 27710
      • Duke University
      • Contact: Elyse Wilson; Phone Number: (919) 681-8879; Email: elyse.wilson@duke.edu
      • Principal Investigator: Adam DeVore, MD, MHS, FHFSA, FAHA, FACC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health System
      • Contact: Alyson Brown; Phone Number: 215-662-2128; Email: alyson.brown@pennmedicine.upenn.edu
      • Principal Investigator: Joyce Wald, DO, FACC
  • Tennessee
    • Nashville, Tennessee, United States, 32703
      • Centennial Medical Center
      • Contact: Kristen Kuhn; Phone Number: 615.982.0640; Email: kristen.kuhn2@hcahealthcare.com
      • Principal Investigator: Thomas McRae, MD, FACC
      • Principal Investigator: Zachary J II'Giovine, MD, FACC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 and < 80 years
2. Subject has signed the Informed Consent Form. If the subject has been enrolled via an LAR, the subject must provide assent, the assent will be documented.
3. LVEF ≤ 40%

4. Subject is presenting with decompensated heart failure and meets at least one (1) of the following cardiogenic shock criteria:

   1. Sustained episode of systolic blood pressure ≤ 90 mmHg for at least 30 minutes or need for vasoactive agents to maintain such blood pressure.
   2. Cardiac index (CI) < 2.2 L/min/m2 determined to be secondary to cardiac dysfunction, in the absence of hypovolemia.
   3. Require support with an intra-aortic balloon pump (IABP)
   4. Serum lactate >2 mmol/L

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. Intra-aortic balloon pump (IABP) use >24 hours from the onset of cardiogenic shock if placed at the enrolling site or >48 hours if transferred on IABP prior to enrollment
7. On mechanical circulatory support other than IABP (i.e. ECMO, Impella CP, etc) or on mechanical ventilation for non-procedural reasons prior to enrollment
8. Revascularization or cardiac surgery within 30-days of the index hospitalization date or decision to undergo revascularization or cardiac surgery made prior to enrollment
9. Infiltrative/restrictive cardiomyopathy (sarcoidosis and amyloidosis), hypertrophic cardiomyopathy, constrictive pericarditis, pericardiac tamponade, or fulminant myocarditis (giant cell or immune checkpoint inhibitor)
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 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. Thrombus in the left atrium or ventricle
    4. Infection of the planned procedural access site or suspected systemic active infection.
    5. Severe arterial disease precluding placement of Impella
    6. Presence of Atrial or Ventricular Septal Defect
    7. Left ventricular rupture
    8. Cardiac tamponade
    9. Combined cardiorespiratory failure
22. Intolerance to anticoagulant or antiplatelet therapies, or will refuse blood transfusions.
23. 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 (or assent if LAR) and/or to comply with study procedures.
24. Participation in the active treatment or follow-up phase of another clinical study of an investigational drug or device.
25. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Single arm study; This is a single arm study.	Device: Impella 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.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	HF hospitalization or urgent HF visit	90-days, 180-days, 1-year post-enrollment
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	The composite rate of any of the following device-related serious adverse events: Major vascular access site complication; Major hemolysis; Bleeding, defined as MCS-ARC Type 3 or higher; Structural complication requiring repair; Stroke	Hospital Discharge (within 24 hours), 30-days post-enrollment
Subjects achieving indicated GDMT treatment	Achieving any dose of all four classes	Hospital Discharge(within 24 hours), 90-days, 180-days post-enrollment
% of Subjects achieving optimized GDMT treatment	Achieving at least 50% of the target dose of all four classes	90-days and 180-days post-enrollment
Modified Heart Failure Collaboratory (mHFC) score	Defined by HFC in 2022. Improvement from baseline	Hospital Discharge(within 24 hours), 90-days, 180-days post-enrollment
Rate of GDMT-Related Serious Adverse Events	The composite rate of any of the following GDMT-related serious adverse events: Recurrence or worsening shock; symptomatic hypotension requiring admission; Bradycardia requiring treatment; Hyperkalemia requiring intervention; Ketoacidosis requiring treatment; Need for new renal replacement therapy (RRT)	Hospital Discharge (within 24 hours), 90-days, and 180-days post-enrollment
Quality of life assessed by EQ-5D	improvement from baseline	180-days and 1-year post-discharge
6-Minute Walk Test Distance	improvement from baseline	180-days and 1-year post-discharge
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	NT-proBNP from baseline	Hospital Discharge (within 24 hours), 30-days, and 90-days post-discharge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
% of Subjects achieving optimized GDMT treatment	Achieving any dose of all four classes and at least 50% of the target dose of β-blocker and RASi	Through 1-year post-discharge
Modified Heart Failure Collaboratory (mHFC) score	Defined by HFC in 2022. Improvement from baseline	Through 1-year post-discharge
Rate of GDMT-Related Serious Adverse Events	The composite rate of any of the following GDMT-related serious adverse events: Recurrence or worsening shock; symptomatic hypotension requiring admission; Bradycardia requiring treatment; Hyperkalemia requiring intervention; Ketoacidosis requiring treatment; Need for new renal replacement therapy (RRT)	Through 1-year post-discharge
% of Subjects free from heart replacement	Freedom from durable ventricular assist device (VAD) or heart transplant (HTx)	Through 1-year post-discharge
Rate of subjects with HF hospitalization or urgent HF visit		Through 1-year post-discharge
% of Subjects with cardiovascular mortality and all cause mortality		Through 1-year post-discharge
% of Subjects with all-cause death		Through 1-year post-discharge
Left ventricular ejection fraction (LVEF)	Change from baseline	Through 1-year post-discharge
Left ventricular end-diastolic diameter (LVEDD)	Change from baseline	Through 1-year post-discharge
N-Terminal pro b-type natriuretic peptide (NT-proBNP)	Change from baseline	Through 1-year post-discharge
Quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)	Improvement from baseline	Through 1-year post-discharge
Quality of life assessed by EuroQoL 5-Dimensions 5-Levels (EQ-5D-5L)	Improvement from baseline	Through 1-year post-discharge
6-Minute Walk Test Distance	Improvement from baseline	Through 1-year post-discharge
New York Heart Association (NYHA) heart failure class	Improvement from baseline	Through 1-year post-discharge
Society for Cardiovascular Angiography & Interventions (SCAI) shock stage	Improvement from baseline	Time of device removal
Rate of major device-related adverse events	The composite rate of any of the following device-related serious adverse events: Major vascular access site complication; Major hemolysis; Bleeding, defined as MCS-ARC Type 3 or higher; Structural complication requiring repair; Stroke	Hospital discharge
GDMT Optimization Change Score	Sum of positive therapy changes (+2 for new GDMT initiations, +1 for dose uptitration) and negative therapy changes (-2 for GDMT discontinuation, -1 for dose downtitration) from baseline	Through 1-year post-discharge

Collaborators and Investigators

• Sponsor: Abiomed Inc.
• Collaborators: Johnson & Johnson
• Investigators: Principal Investigator: Adam DeVore, MD, MHS, Duke University; Principal Investigator: Gavin Hickey, MD, University of Pittsburgh; Principal Investigator: Manreet Kanwar, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: April 21, 2025
• First Submitted That Met QC Criteria: May 2, 2025
• First Posted (Actual): May 11, 2025

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cardiovascular Disease; Heart Disease; Mechanical Circulatory Support; Impella 5.5; Guideline Directed Medical Therapy; Heart Failure Cardiogenic Shock; Reduced Ejection Fraction Heart Failure
• Additional Relevant MeSH Terms: Vascular Diseases; Pathologic Processes; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Shock; Pathological Conditions, Signs and Symptoms; Heart Failure; Cardiovascular Diseases; Heart Diseases; Shock, Cardiogenic; Heart Failure, Systolic
• Other Study ID Numbers: INTeGRATE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No