Clinical trial NCT06965504: INitiation and Titration of Guideline Directed Medical TheRApy in HearT Failure Cardiogenic Shock With ImpElla 5.5 for Cardiac Recovery
Official title: Initiation and Titration of Guideline Directed Medical Therapy in Heart Failure Cardiogenic Shock With Impella 5.5 for Cardiac Recovery: INTeGRATE
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Heart Failure
Cardiogenic Shock
Reduced Ejection Fraction Heart Failure
Keywords: Impella 5.5
Heart Failure Cardiogenic Shock
Reduced Ejection Fraction Heart Failure
Mechanical Circulatory Support
Cardiovascular Disease
Heart Disease
Guideline Directed Medical Therapy
Lead sponsor: Abiomed Inc.
Sponsor class: INDUSTRY
Collaborators: name: Johnson & Johnson
First posted: 2025-05-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study will evaluate if Impella 5.5® support in heart failure reduced ejection fraction (HFrEF) patients presenting with decompensated heart failure (HF) and cardiogenic shock will facilitate the initiation and optimization of guideline directed medical therapy (GDMT) during the hospital stay and post-discharge.

Detailed description: This is a prospective, single arm, multi-center, post-market, on-label study. Patients presenting with HFrEF who are not on adequate GDMT and who are presenting with heart failure cardiogenic shock will be evaluated for inclusion. The study objectives are to evaluate the impact of Impella 5.5 support on GDMT up-titration during support, at discharge, and at 90-days post-discharge and to evaluate the feasibility of Impella 5.5 combined with optimal GDMT to improve heart recovery in patients with decompensated heart failure. Outcomes will be measured up to one-year post-hospital discharge.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 and \< 75 years
2. Subject has signed the Informed Consent
3. LVEF ≤ 40%
4. History of HF \<5 years
5. Subject is presenting with decompensated heart failure and meets one 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. Or serum lactate \> 2 mmol/L
   3. Or a cardiac index (CI) \< 2.2 L/min/m2 determined to be secondary to cardiac dysfunction, in the absence of hypovolemia
   4. Or required support with an intra-aortic balloon pump (IABP)
6. Subject has inadequate heart failure GDMT based on the most recent outpatient prescription prior to index admission as determined by the treating cardiologist and the Eligibility Committee, defined as:

   1. On 2 or less of the evidence-based GDMT (BB, MRA, SGLT2i, and RASi)
   2. If on β-blocker and RASi, at least one of the two medications is \<50% of maximal 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. 2nd or 3rd degree AV block, unless pacemaker is in place
   5. Angioedema, hereditary or idiopathic
   6. Pregnancy, known or confirmed by a pregnancy test if of child bearing potential.
2. Cardiogenic shock due to myocardial infarction prior to enrollment
3. Mixed shock, septic shock, or shock from non-cardiac origins
4. Severe Cardiogenic Shock, defined as meeting one or more of the below prior to enrollment:

   1. SCAI stage E per Study Definition (Appendix C)
   2. Serum lactate \> 8mmol/L
   3. On mechanical circulatory support (not including IABP) or on mechanical ventilation for non-procedural reasons.
   4. Experiencing pulseless electrical activity (PEA) or refractory ventricular tachycardia (VT)/ventricular fibrillation (VF)
   5. Severe acidosis (pH \< 7.2 or bicarbonate \< 10mEq/L)
5. In cardiac arrest prior to enrollment
6. Revascularization or cardiac surgery within 90-days of the index hospitalization date or decision to undergo revascularization or cardiac surgery made prior to enrollment.
7. Inflammatory and infiltrative cardiomyopathy (CM) including myocarditis, restrictive CM, constrictive pericarditis, or hypertrophic CM including sarcoidosis and amyloidosis.
8. Adult congenital heart disease without appropriate surgical correction
9. Structural or anatomical abnormalities that cannot be modified as determined by the treating cardiologist, including severe primary mitral regurgitation (MR) .
10. Severe RV dysfunction, per Study Definition (Appendix C), requiring mechanical or inotropic support prior to enrollment.
11. Severe dilatation of the LV with LVEDD greater than 8.0cm
12. History of heart transplant or listed for heart transplant prior to enrollment.
13. Planned to be implanted with a permanent VAD within 90-days of the index hospitalization date.
14. Continuous outpatient inotropic support prior to the index hospitalization date.
15. Planned to pursue palliative care or hospice, or life expectancy of less than 2 years due to non-cardiac illness at the time of index hospitalization date.
16. ICD upgrade to BiV, or implantation of CRT within 30-days of the index hospitalization date.
17. Currently on dialysis, or has pre-existing end-stage chronic kidney disease (stage 4 or above), or has hereditary, infectious, or autoimmune nephropathy.
18. Pre-existing liver dysfunction defined as: presence of liver cirrhosis or alcoholic hepatitis, or presence of acute liver failure or acute hepatitis not due to cardiogenic shock.
19. Pre-existing pulmonary disease requiring home oxygen
20. History of stroke or intracranial hemorrhage ≤ 90 days of the index hospitalization date, or a history of cerebrovascular disease with significant (\> 80%) uncorrected carotid stenosis, or any permanent neurological deficit with mRS score \>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 (including post-infarct VSD)
    7. Left ventricular rupture
    8. Cardiac tamponade I. Combined cardiorespiratory failure
22. Known contraindication to heparin (i.e., heparin induced thrombocytopenia (HIT)) or intolerance to anticoagulant or antiplatelet therapies.
23. Allergies or contraindications to contrast agents unless can be adequately medicated.
24. History of bleeding diathesis or known coagulopathy, any GU or GI bleed within 90-days of the index hospitalization date or will refuse blood transfusions.
25. 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.
26. Participation in the active treatment or follow-up phase of another clinical study of an investigational drug or device that has not met its primary endpoint.
27. Subject belongs to a vulnerable population, such as such as prisoners, individuals with impaired decision making, or economically or educationally disadvantaged persons.

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Primary outcomes:
measure: % of Subjects achieving indicated GDMT treatment
timeFrame: Hospital discharge
Secondary outcomes:
Other outcomes:
measure: % of Subjects achieving optimized GDMT treatment
timeFrame: Through 1-year post-discharge
measure: Modified Heart Failure Collaboratory (mHFC) score
timeFrame: Through 1-year post-discharge
measure: Rate of GDMT-Related Serious Adverse Events
timeFrame: Through 1-year post-discharge
measure: % of Subjects free from heart replacement
timeFrame: Through 1-year post-discharge
measure: Rate of subjects with HF hospitalization or urgent HF visit
timeFrame: Through 1-year post-discharge
measure: % of Subjects with cardiovascular mortality and all cause mortality
timeFrame: Through 1-year post-discharge
measure: % of Subjects with all-cause death
timeFrame: Through 1-year post-discharge
measure: Left ventricular ejection fraction (LVEF)
timeFrame: Through 1-year post-discharge
measure: Left ventricular end-diastolic diameter (LVEDD)
timeFrame: Through 1-year post-discharge
measure: N-Terminal pro b-type natriuretic peptide (NT-proBNP)
timeFrame: Through 1-year post-discharge
measure: Quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: Through 1-year post-discharge
measure: Quality of life assessed by EuroQoL 5-Dimensions 5-Levels (EQ-5D-5L)
timeFrame: Through 1-year post-discharge
measure: 6-Minute Walk Test Distance
timeFrame: Through 1-year post-discharge
measure: New York Heart Association (NYHA) heart failure class
timeFrame: Through 1-year post-discharge
measure: Society for Cardiovascular Angiography & Interventions (SCAI) shock stage
timeFrame: Time of device removal
measure: Rate of major device-related adverse events
timeFrame: Hospital discharge
measure: GDMT Optimization Change Score
timeFrame: Through 1-year post-discharge
Locations:
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Minneapolis
country: United States
facility: Abbott Northwestern
state: Minnesota
city: New Brunswick
country: United States
facility: Rutgers-Robert Wood Johnson Medical School
state: New Jersey
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System
state: Pennsylvania
city: Nashville
country: United States
facility: Centennial Medical Center
state: Tennessee
Study officials:
affiliation: Duke University
name: Adam DeVore, MD, MHS
role: PRINCIPAL_INVESTIGATOR
References: