Unloading in Heart Failure Cardiogenic Shock

Study Overview
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Brief Summary
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The purpose of this research study is to evaluate whether timely and aggressive temporary Mechanical Circulatory Support (tMCS) through the Impella 5.5® in patients with acute decompensated heart failure complicated by cardiogenic shock (ADHF-CS) has the potential to reduce the HF-CS related clinical events compared to the current standard of care.

Detailed Description
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To demonstrate the efficacy of timely temporary mechanical left ventricular unloading with the Impella 5.5® assist device in patients with acute decompensated heart failure complicated by cardiogenic shock (ADHF-CS) vs. current standard of (pharmacological) care

Official Title
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Use of mechaNical Left ventricuLar unlOading in Acute decompensateD Heart Failure Complicated by Cardiogenic Shock - the UNLOAD HF-CS Trial.

Conditions
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Cardiogenic Shock

Intervention / Treatment
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* Device: Impella 5.5
* Drug: Inotropes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Evidence of HFrEF according to ESC HF guidelines (LVEF ≤ 35%) 2. Signs of (persistent) congestion (elevated CVP, edema, rales, ascites, pleural effusion) 3. Evidence of CS with presence of at least 2 of the 3 following: Hypotension systolic blood pressure <90 mmHg for at least 30 min OR mean arterial pressure <60 mmHg for at least 30 min Hypoperfusion lactate > 2.0 mmol/L (two consecutive values > 2 mmol/L with at least 30 min between samples, with non-decreasing trend on if on (steady doses of) inotropes and/or vasopressors) amino-L-transferase >200 U/L (two consecutive values > 200 Ul/L with at least 30 min between samples, with non-decreasing trend if on (steady doses of) inotropes and/or vasopressors) creatinine rise ≥ 0.3 mg/dl/24h ( 26,53 μmol/L) oliguria (≤ 0,5 ml/kg/h, ≤ 720 ml/24 h) Inotropes/vasoactives (use of) Exclusion Criteria: Contraindications for Impella 5.5 Severe concomitant RV failure Grade IV mitral regurgitation eligible for surgical treatment Dialysis for end-stage renal failure Acute coronary syndrome (type 1, AMI) Bradycardia and AV blocks necessitating pacemaker implantation HD parameters and biochemistry alterations as specifically defined for SCAI CS E Combined cardiorespiratory failure Resuscitated (OHCA/PEA) History of CVA or TIA within previous 90 days History of acute myocardial infarction within previous 30 days History of bleeding diathesis or known coagulopathy (including heparin-induced thrombo-cytopenia), any recent GU or GI bleed, or will refuse blood transfusions Inflammatory Active systemic infections Acute myocarditis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Impella 5.5<br>ADHF-CS patients who are in the experimental arm will be treated with an Impella 5.5 (+/- standard of care) | Device: Impella 5.5<br>* temporary Mechanical Circulatory Support (tMCS)<br>|
| Other: Standard of care<br>ADHF-CS patients who are in the control arm will be treated with escalating doses of inotropes (standard of care) | Drug: Inotropes<br>* Enoximone, Dobutamine, Dopamine, Milrinone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of all-cause mortality, renal replacement therapy and rehospitalization or urgent visit for heart failure (Efficacy - Primary Combined Clinical Endpoint) | Number of patients suffering from any of: all-cause death, renal replacement therapy and rehospitalization or urgent hospital visit for heart failure up to 90 days | baseline to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-hospital mortality (Efficacy - Secondary Endpoint) | Number of patients suffering from cardiac death and non-cardiac death and undetermined death during hospitalisation | baseline to 28 days | 
| In-hospital Worsening Heart Failure (Efficacy - Secondary Endpoint) | Number of patients with progression to SCAI CS stage D OR E (depending on stage directly after randomization) | baseline to 28 days | 
| Cardiac mortality (Efficacy - Secondary Endpoint) | Number of patients that died of any cause at 90 days and 1 year | baseline to 1 year | 
| All-cause mortality (Efficacy - Secondary Endpoint) | Number of patients that died of any cause at 90 days and 1 year | baseline to 1 year | 
| Mechanical ventillation (Efficacy - Secondary Endpoint) | Number of patients that were mechanically ventilated during hospitalization, up to day 90 and 1 year | baseline to 1 year | 
| Renal replacement therapy (Efficacy - Secondary Endpoint) | Number of patients that received renal replacement therapy during hospitalization, up to day 90 and 1 year | baseline to 1 year | 
| Hospitalization or urgent hospital visit for heart failure (Efficacy - Secondary Endpoint) | Number of patients that were hospitalized or had an urgent hospital visit for heart failure up to day 30, 60 and 1 year | baseline to 1 year | 
| Urgent / rescue MCS implantation (permanent) (Efficacy - Secondary Endpoint) | Number of patients that received a permanent MCS device implantation up to day 90 and 1 year | baseline to 1 year | 
| Hospitalization time (Efficacy - Secondary Endpoint) | Lenght of index hospitalization for HF-CS in days | baseline to 28 days | 
| Vasoactive Inotropic Score (maximal) (Efficacy - Secondary Endpoint) | Maximal VIS during hospitalization | baseline to 28 days | 
| LVAD / Heart transplantation (Efficacy - Secondary Endpoint) | Number of patients that received heart treplacement therapy up to discharge, 90 days and 1 year | baseline to 1 year | 
| KCCQ-12 (Efficacy - Secondary Endpoint) | Average KCCQ-12 at 90 days and 1 year | 90 days, 1 year | 
| Stroke or TIA (Safety - Secondary Endpoint) | Number of patients that developed a stroke or TIA up to discharge | baseline to 28 days | 
| Major Bleeding (Safety - Secondary Endpoint) | Number of patients that developed a major bleed up to discharge | baseline to 28 days | 
| Major vascular events (Safety - Secondary Endpoint) | Number of patients that developed a major vascular event up to discharge | baseline to 28 days | 
| Extremity ischemia (Safety - Secondary Endpoint) | Number of patients that developed limb ischemia up to discharge | baseline to 28 days | 
| Hemolysis (Safety - Secondary Endpoint) | Number of patients diagnosed with hemolysis up to discharge | baseline to 28 days | 
| Insertion site infection (Safety - Secondary Endpoint) | Number of patients that developed an infection at the insertion site up to discharge | baseline to 28 days | 
| Aortic valve injury (Safety - Secondary Endpoint) | Number of patients that developed aortic valve insufficiency (by echo) up to day 90 | baseline to 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unloading, Acute Decompensated Heart Failure, Cardiogenic Shock, temporary Mechanical Circulatory Support (tMCS), Inotropes