Unloading in Heart Failure Cardiogenic Shock (UNLOAD HF-CS)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiogenic Shock
• Intervention / Treatment: Drug: Inotropes; Device: Impella 5.5

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 Type: Interventional
• Enrollment (Estimated): 456
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alexander Nap, MD PhD; Phone Number: +31(0)614102081; Email: a.nap@amsterdamumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Academical Medical Center (AMC)
    • Contact: Jose PS Henriques, MD PhD
  • Amsterdam, Netherlands
    • VU University Medical Center (VUMC)
    • Contact: Alexander Nap, MD PhD
  • Groningen, Netherlands
    • Univerity Medical Center Groningen (UMCG)
    • Contact: Kevin Damman, MD PhD
  • Leiden, Netherlands
    • Leids Universitair Medisch Centrum (LUMC)
    • Contact: Jose Montero-Cabezas, MD PhD
  • Utrecht, Netherlands
    • University Medical Center Utrecht (UMCU)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

1. Hypotension

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

2. 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)
3. 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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: Abiomed Inc.
• Investigators: Principal Investigator: Alexander Nap, MD PhD, Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: September 21, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 29, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Inotropes; Cardiogenic Shock; Acute Decompensated Heart Failure; Unloading; temporary Mechanical Circulatory Support (tMCS)
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Heart Failure; Shock; Shock, Cardiogenic
• Other Study ID Numbers: NL84199.018.23

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: No
• product manufactured in and exported from the U.S.: No