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

Overview

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. 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.

Interventions

• 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.

Primary outcome measures

• Composite of all-cause death, HF hospitalization, and heart replacement (heart transplantation or durable LVAD implantation) [Time frame: Timeframe: 180-days post-enrollment]

Secondary outcome measures (12)

• Composite of all-cause death and heart replacement [Time frame: 90-days, 180-days, 1-year post-enrollment]
• Composite of all-cause death, HF hospitalization, and heart replacement [Time frame: 90-days, 1-year post-enrollment]
• All-cause mortality [Time frame: Hospital Discharge (within 24 hours) , 90-days, 180-days, 1-year post-enrollment]
• Cardiovascular mortality [Time frame: Hospital Discharge (within 24 hours), 90-days, 180-days, 1-year post-enrollment]
• Worsening heart failure [Time frame: 90-days, 180-days, 1-year post-enrollment]
• Composite of all-cause death and worsening heart failure [Time frame: 90-days, 180-days, 1-year post-enrollment]
• Non-HF cardiovascular hospitalization [Time frame: 90-days, 180-days, 1-year post-enrollment]
• All cardiovascular hospitalization [Time frame: 90-days, 180-days, 1-year post-enrollment]
• Composite of all-cause death and all cardiovascular hospitalization [Time frame: 90-days, 180-days, 1-year post-enrollment]
• Rate of major device-related adverse events [Time frame: Hospital Discharge (within 24 hours), 30-days post-enrollment]
• Subjects achieving indicated GDMT treatment [Time frame: Hospital Discharge(within 24 hours), 90-days, 180-days post-enrollment]
• % of Subjects achieving optimized GDMT treatment [Time frame: 90-days and 180-days post-enrollment]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 and < 80 years
• 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.
• LVEF ≤ 40%
• Subject is presenting with decompensated heart failure and meets at least one (1) of the following cardiogenic shock criteria:

• Sustained episode of systolic blood pressure ≤ 90 mmHg for at least 30 minutes or need for vasoactive agents to maintain such blood pressure.
• Cardiac index (CI) < 2.2 L/min/m2 determined to be secondary to cardiac dysfunction, in the absence of hypovolemia.
• Require support with an intra-aortic balloon pump (IABP)
• Serum lactate >2 mmol/L
• Subject has inadequate heart failure GDMT based on the most recent outpatient prescription prior to index admission, defined as:

• On 2 or less of the 4-Pillar HF Drug Classes (BB, MRA, SGLT2i, and RASi)
• If on BB and RASi, at least one of the two medications is < 50% of the maximal target dose.

Exclusion criteria

• Underlying unmodifiable conditions that limit initiation of GDMT prior to enrollment, including but not limited to:

• 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.

• Known bilateral renal artery stenosis
• Type 1 diabetes
• 2o or 3o AV block, unless pacemaker is in place
• Angioedema, hereditary or idiopathic
• Pregnancy, known or confirmed by a pregnancy test if of childbearing potential
• ST-segment elevation or acute coronary syndrome (ACS) prior to enrollment
• Septic shock, shock from non-cardiac origins, or mixed shock
• SCAI Stage E cardiogenic shock per study definition (Appendix C) prior to enrollment
• In cardiac arrest prior to enrollment
• 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
• On mechanical circulatory support other than IABP (i.e. ECMO, Impella CP, etc) or on mechanical ventilation for non-procedural reasons prior to enrollment
• Revascularization or cardiac surgery within 30-days of the index hospitalization date or decision to undergo revascularization or cardiac surgery made prior to enrollment
• Infiltrative/restrictive cardiomyopathy (sarcoidosis and amyloidosis), hypertrophic cardiomyopathy, constrictive pericarditis, pericardiac tamponade, or fulminant myocarditis (giant cell or immune checkpoint inhibitor)
• Complex adult congenital heart disease
• Primary severe valvular disease
• Predominant RV dysfunction per Investigator's discretion
• History of heart transplant or listed for heart transplant or planned for heart transplantation prior to enrollment.
• Planned to be implanted with a permanent VAD within 180-days of the index hospitalization date.
• Continuous outpatient inotropic support prior to the index hospitalization date.
• 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.
• 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.
• Pre-existing liver disease including liver cirrhosis, alcoholic hepatitis, metabolic dysfunction associated steatohepatitis (MASH), or genetic liver disease.
• Pre-existing pulmonary disease with oxygen dependency.
• 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.
• Any contraindication that precludes placing an Impella 5.5®, including but not limited to:

• Aortic valve stenosis/calcification with orifice area ≤ 0.6cm2 or aortic insufficiency of any grade greater than mild on pre-procedure echocardiography.
• Presence of mechanical aortic valve or heart constrictive device
• Thrombus in the left atrium or ventricle
• Infection of the planned procedural access site or suspected systemic active infection.
• Severe arterial disease precluding placement of Impella
• Presence of Atrial or Ventricular Septal Defect
• Left ventricular rupture
• Cardiac tamponade
• Combined cardiorespiratory failure
• Intolerance to anticoagulant or antiplatelet therapies, or will refuse blood transfusions.
• 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.
• Participation in the active treatment or follow-up phase of another clinical study of an investigational drug or device.
• 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• Tampa General Hospital — Tampa
• Abbott Northwestern — Minneapolis
• Rutgers-Robert Wood Johnson Medical School — New Brunswick
• Atrium Health — Charlotte
• Duke University — Durham
• University of Pennsylvania Health System — Philadelphia
• Centennial Medical Center — Nashville

Identifiers

NCT: NCT06965504 · INTeGRATE

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗