Unloading in Heart Failure Cardiogenic Shock

Not Applicable

Not yet recruiting

• Conditions: Cardiogenic Shock
• Interventions: Device: Impella 5.5; Drug: Inotropes

• Registration Number: NCT05064202
• Lead Sponsor: Amsterdam UMC, location VUmc

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2021-08-26
• Study First Submitted QC: 2021-09-21
• Study First Posted: 2021-10-01
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-29
• Last Update Posted: 2023-08-01
• Study Start: 2023-10-01
• Primary Completion: 2027-10-01
• Study Completion: 2028-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 456

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:

2. Hypotension

   1. systolic blood pressure <90 mmHg for at least 30 min OR
   2. mean arterial pressure <60 mmHg for at least 30 min

3. Hypoperfusion

   1. 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)
   2. 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)
   3. creatinine rise ≥ 0.3 mg/dl/24h ( 26,53 μmol/L)
   4. oliguria (≤ 0,5 ml/kg/h, ≤ 720 ml/24 h)

4. Inotropes/vasoactives (use of)

Exclusion Criteria

1. Contraindications for Impella 5.5
2. Severe concomitant RV failure
3. Grade IV mitral regurgitation eligible for surgical treatment
4. Dialysis for end-stage renal failure
5. Acute coronary syndrome (type 1, AMI)
6. Bradycardia and AV blocks necessitating pacemaker implantation
7. HD parameters and biochemistry alterations as specifically defined for SCAI CS E
8. Combined cardiorespiratory failure
9. Resuscitated (OHCA/PEA)
10. History of CVA or TIA within previous 90 days
11. History of acute myocardial infarction within previous 30 days
12. History of bleeding diathesis or known coagulopathy (including heparin-induced thrombo-cytopenia), any recent GU or GI bleed, or will refuse blood transfusions
13. Inflammatory
14. Active systemic infections
15. Acute myocarditis

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Impella 5.5	Impella 5.5	ADHF-CS patients who are in the experimental arm will be treated with an Impella 5.5 (+/- standard of care)
Standard of care	Inotropes	ADHF-CS patients who are in the control arm will be treated with escalating doses of inotropes (standard of care)

Primary Outcome Measures

Name	Time	Method
Composite of all-cause mortality, renal replacement therapy and rehospitalization or urgent visit for heart failure (Efficacy - Primary Combined Clinical Endpoint)	baseline to 90 days	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

Secondary Outcome Measures

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

Trial Locations

Locations (5)

Academical Medical Center (AMC); 🇳🇱 Amsterdam, Netherlands

VU University Medical Center (VUMC); 🇳🇱 Amsterdam, Netherlands

Univerity Medical Center Groningen (UMCG); 🇳🇱 Groningen, Netherlands

Leids Universitair Medisch Centrum (LUMC); 🇳🇱 Leiden, Netherlands

University Medical Center Utrecht (UMCU); 🇳🇱 Utrecht, Netherlands