Levosimendan In Ambulatory Heart Failure Patients

NCT ID: NCT04705337

Last Updated: 2025-05-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-15
• Study Completion Date: 2024-08-15

Brief Summary

The objective of the study is to determine the efficacy of repeated infusions of levosimendan in the group of outpatients with advanced systolic heart failure (HF).

Detailed Description

It is a multicentre, randomized, double-blind, placebo-controlled study. 350 subjects will be included (in 12 or more medical centers) with severe HF, ejection fraction ≤35%, in New York Heart Association class III or IV. The other inclusion criteria concern: hospitalization for the HF decompensation in the last 3 months and a reduced six-minute walk test <350m or elevated NTproBNP ≥1000 pg / mL. To the European Society of Cardiology-guided, individually optimized medical therapy (OMT) the investigational product (IP) will be added. The subjects will be randomly assigned to one of the study group: 175 to the levosimendan arm and 175 to the placebo arm. The intervention studied in LEIA-HF trial is the administration of levosimendan as a continuous iv. infusion, every 4 weeks for 48 weeks (12 infusions in total). All study participants will also continue OMT. In the second phase of the study, after completing the levosimendan / placebo infusions, another 6 visits are planned, still double-blind, every 4 weeks, to assess the safety of treatment discontinuation (with optional return to the infusions by the Investigator when additional criteria for HF decompensation are met).

The efficacy of the treatment will be assessed after 52 weeks, 4 weeks after the last levosimendan / placebo administration.

Conditions

Heart Failure New York Heart Association Class III; Heart Failure New York Heart Association Class IV; Heart Failure, Systolic; Heart Failure With Reduced Ejection Fraction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Levosimendan

administration of levosimendan

Group Type: EXPERIMENTAL

Levosimendan

Intervention Type: DRUG

administration of levosimendan as a continuous iv. infusion, every 4 weeks for 48 weeks (12 infusions in total)

Placebo

administration of placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

administration of glucose as a continuous iv. infusion, every 4 weeks for 48 weeks (12 infusions in total)

Interventions

Levosimendan

administration of levosimendan as a continuous iv. infusion, every 4 weeks for 48 weeks (12 infusions in total)

Intervention Type: DRUG

Placebo

administration of glucose as a continuous iv. infusion, every 4 weeks for 48 weeks (12 infusions in total)

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Informed consent obtained before any trial activities
• Male or female, age ≥ 18 years at the time of signing informed consent
• Left ventricle ejection fraction ≤ 35%
• Hospitalization due to worsening of HF within the last 3 months
• New York Heart Association functional class III or outpatient IV
• Individually optimized pharmacotherapy, based on the current European Society of Cardiology recommendations, stable for at least 1 month prior to randomization, according to the knowledge and experience of the qualifying clinician
• Distance covered in six-minute walk test <350m OR NTproBNP concentration ≥ 1000 pg/mL
• In the opinion of the Investigator, the patient does not currently require hospitalization
• Patient protected with an implantable device capable of terminating life-threatening arrhythmias and conduction disturbances (ICD or cardiac resynchronisation therapy-D/P), if indicated and the patient consents to implantation.

Exclusion Criteria

• Known or suspected hypersensitivity to trial products or related products,
• Restrictive or hypertrophic cardiomyopathy, uncorrected severe valvular disease, potentially reversible cause of HF
• Hypotension with symptoms of tissue hypoperfusion
• Uncontrolled hypertension
• Planned revascularization or other surgical treatment of HF within the next year
• Advanced chronic kidney disease
• Features of liver damage
• Severe chronic lung disease with features of respiratory distress or severe abnormal spirometry or home oxygen treatment
• Accompanying chronic diseases with poor prognosis
• Paroxysmal supraventricular tachycardia, paroxysmal ventricular tachycardia, torsade de pointes, advanced atrioventricular blocks within one month prior to screening
• Receipt of any investigational product within 30 days before screening visit
• Any disorder, which in the investigator's opinion may jeopardise subject's safety or compliance with the study protocol and procedures

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical Research Agency, Poland

OTHER_GOV

Sponsor Role: collaborator

University of Opole

OTHER

Sponsor Role: collaborator

Medical University of Lodz

OTHER

Sponsor Role: collaborator

Poznan University of Medical Sciences

OTHER

Sponsor Role: collaborator

Nicolaus Copernicus University

OTHER

Sponsor Role: collaborator

National Institute of Cardiology, Warsaw, Poland

OTHER

Sponsor Role: collaborator

Azienda Ospedaliera dei Colli

OTHER

Sponsor Role: collaborator

John Paul II Hospital, Krakow

OTHER

Sponsor Role: collaborator

Medical University of Bialystok

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Agnieszka Tycińska, Prof. MD

Role: STUDY_CHAIR

Medical University of Bialystok

Marek Gierlotka, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

University of Opole

Jarosław Kasprzak, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Łódź

Jacek Kubica, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Nicolaus Copernicus University in Toruń

Grzegorz Grześk, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Nicolaus Copernicus University in Toruń

Jadwiga Nessler, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

John Paul II Hospital, Krakow

Janina Stępińska, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Cardinal Stefan Wyszyński Institute of Cardiology

Ewa Straburzyńska-Migaj, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Poznan University of Medical Sciences

Locations

Medical University of Bialystok Clinical Hospital

Bialystok, , Poland

Medical University Hospital No.1

Bydgoszcz, , Poland

Medical University Hospital No.2

Bydgoszcz, , Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Górnośląskie Centrum Medyczne Śląskiego Uniwersytetu Medycznego

Katowice, , Poland

Szpital Uniwersytecki w Krakowie

Krakow, , Poland

John Paul II Hospital

Krakow, , Poland

Provincial Specialist Hospital named after Dr. Wł. Biegański

Lodz, , Poland

Medical University Hospital

Opole, , Poland

University Hospital of Lord's Transfiguration

Poznan, , Poland

Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego

Warsaw, , Poland

Cardinal Stefan Wyszyński Institute of Cardiology

Warsaw, , Poland

Uniwersytecki Szpital Kliniczny

Wroclaw, , Poland

Śląskie Centrum Chorób Serca

Zabrze, , Poland

Countries

Poland

Other Identifiers

2019/ABM/01/00017

Identifier Type: -

Identifier Source: org_study_id