UNLOAD-HF: Mechanical Left Ventricular Unloading in Acute Decompensated Heart Failure

Sponsor

Amsterdam UMC, location VUmc (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05064202

Collaborator

Abiomed Inc. (Industry)

456

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this research study is to evaluate whether initial temporary circulatory support through the Impella CP® system in patients with acute decompensated heart failure (ADHF) and in-hospital worsening heart failure (WHF) in whom inotropes are deemed necessary, has the potential to reduce the heart failure related-clinical events compared to the current standard of care.

Condition or Disease	Intervention/Treatment	Phase
Acute Decompensated Heart Failure	Device: Impella CP Drug: Inotropes	N/A

Detailed Description

To demonstrate the efficacy of primary percutaneous mechanical left ventricular unloading with the Impella CP® assist device in patients with acute decompensated heart failure (ADHF) and in-hospital worsening heart failure (WHF) vs. current standard of care with inotropes as first-line escalating therapy.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

456 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Use of mechaNical Left ventricuLar unlOading in Acute decompensateD Heart Failure; the UNLOAD-HF Trial.

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Feb 1, 2026

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Impella CP ADHF-patients with in-hospital WHF in whom escalation therapy with inotropes is deemed necessary and who are in the experimental arm will be treated with an Impella CP (+/- standard of care)	Device: Impella CP percutaneous Mechanical Circulatory Support (pMCS), percutaneous Left Ventricular Assist Device (pLVAD)
Other: Standard of care ADHF-patients with in-hospital WHF in whom escalation therapy with inotropes is deemed necessary and who are in the control arm will be treated with inotropes (standard of care)	Drug: Inotropes Enoximone, Dobutamine, Dopamine, Milrinone

Arm

Intervention/Treatment

Experimental: Impella CP

ADHF-patients with in-hospital WHF in whom escalation therapy with inotropes is deemed necessary and who are in the experimental arm will be treated with an Impella CP (+/- standard of care)

Device: Impella CP

percutaneous Mechanical Circulatory Support (pMCS), percutaneous Left Ventricular Assist Device (pLVAD)

Other: Standard of care

ADHF-patients with in-hospital WHF in whom escalation therapy with inotropes is deemed necessary and who are in the control arm will be treated with inotropes (standard of care)

Drug: Inotropes

Enoximone, Dobutamine, Dopamine, Milrinone

Outcome Measures

Primary Outcome Measures

Composite of all-cause mortality, mechanical ventillation, renal replacement therapy and rehospitalisation or urgent visit for heart failure (Efficay - Primary Combined Clinical Endpoint) [baseline to 60 days]
Number of patients suffering from any of: all-cause death, mechanical ventillation, renal replacement therapy and rehospitalisation or urgent hospital visit for heart failure up to 60 days

Secondary Outcome Measures

Pulmonary capillary wedge pressure (PCWP) and right arterial pressure (RAP) < 30mmHg (Efficacy - Key Secondary Endpoint) [48 hours]
Number of patients achieving a combined PCWP (mmHg) and RAP (mmHg) below 30mmHg determined at 48 hours
PCWP(basline) - 25% (Efficacy - Key Secondary Endpoint) [48 hours]
Number of patients achieving a PCWP (mmHg) that has dropped 25% from baseline PCWP (mmHg) determined at 48 hours
PCWP(baseline) - 5mmHg (Efficacy - Key Secondary Endpoint) [48 hours]
Number of patients achieving a PCWP (mmHg) that has dropped 5mmHg from baseline PCWP (mmHg) determined at 48 hours
All-cause mortality (Efficacy - Secondary Endpoint) [baseline to 1 year]
Number of patients that died of any cause during hospitalisation, up to day 30, 60 and 1 year
Mechanical ventillation (Efficacy - Secondary Endpoint) [baseline to 1 year]
Number of patients that were mechanically ventilated during hospitalisation, up to day 30, 60 and 1 year
Renal replacement therapy (Efficacy - Secondary Endpoint) [baseline to 1 year]
Number of patients that received renal replacement therapy during hospitalisation, up to day 30, 60 and 1 year
Hospitalisation or urgent hospital visit for heart failure (Efficacy - Secondary Endpoint) [baseline to 1 year]
Number of patients that were hospitalised or had an urgent hospital visit for heart failure up to day 30, 60 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 30, 60 and 1 year
Hospitalisation time (Efficacy - Secondary Endpoint) [baseline to discharge, on average 15 days]
Lenght of index hospitalisation for decompensated heart failure in days
Heart transplantation (Efficacy - Secondary Endpoint) [baseline to 1 year]
Number of patients that were transplanted up to day 30, 60 and 1 year
Stroke or TIA (Safety - Secondary Endpoint) [baseline to 1 year]
Number of patients that developed a stroke or TIA up to day 30, 60 and 1 year
Major Bleeding (Safety - Secondary Endpoint) [baseline to 1 year]
Number of patients that developed a major bleed up to day 30, 60 and 1 year
Major vascular events (Safety - Device Related Secondary Endpoint) [baseline to 30 days]
Number of patients that developed a major vascular event up to day 30
Limb ischemia (Safety - Device Related Secondary Endpoint) [baseline to 30 days]
Number of patients that developed limb ischemia up to day 30
Hemolysis (Safety - Device Related Secondary Endpoint) [baseline to 30 days]
Number of patients diagnosed with hemolysis up to day 30
Insertion site infection (Safety - Device Related Secondary Endpoint) [baseline to 30 days]
Number of patients that developed an infection at the insertion site up to day 30
Aortic valve injury (Safety - Device Related Secondary Endpoint) [baseline to 30 days]
Number of patients that developed aortic valve insufficiency (by echo) up to day 30

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Evidence of HFrEF according to ESC HF guidelines, preferably LVEF ≤ 35%
Evidence of in-hospital worsening heart failure requiring escalation of inotropic therapy according to the treating heart failure cardiologist based on at least 3 / 4 predefined hemodynamic and clinical criteria
No previous episodes of inotropic treatment during current admission or within the last month
Age: 18 - 80 years

Exclusion Criteria:

Contraindications for Impella CP
Severe concomitant RV failure
Grade IV mitral regurgitation eligible for surgical treatment
Contraindications for inotropic usage
Dialysis for end-stage renal failure
Acute coronary syndrome
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
Active on transplant waiting list

Contacts and Locations

Locations

	Site	City	Country
1	Academical Medical Center (AMC)	Amsterdam	Netherlands
2	VU University Medical Center (VUMC)	Amsterdam	Netherlands
3	Univerity Medical Center Groningen (UMCG)	Groningen	Netherlands
4	Leids Universitair Medisch Centrum (LUMC)	Leiden	Netherlands
5	St Antonius Hospital	Nieuwegein	Netherlands
6	Radboud University Medical Center (RadboudMC)	Nijmegen	Netherlands
7	Erasmus Medical Center (ErasmusMC)	Rotterdam	Netherlands
8	University Medical Center Utrecht (UMCU)	Utrecht	Netherlands