Levosimendan In Ambulatory Heart Failure Patients (LEIA-HF)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure, Systolic; Heart Failure With Reduced Ejection Fraction; Heart Failure New York Heart Association Class IV; Heart Failure New York Heart Association Class III
• Intervention / Treatment: Drug: Levosimendan; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 350
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Agnieszka Tycińska, Prof.; Phone Number: +48 85 831 8656; Email: agnieszka.tycinska@umb.edu.pl
• Study Contact Backup: Name: Andrzej Malkowski, PhD; Phone Number: +48 85 686 5122; Email: andrzej.malkowski@umb.edu.pl

Study Locations

• Poland
  • Bialystok, Poland, 15-276
    • Medical University of Bialystok Clinical Hospital
    • Principal Investigator: Agnieszka Tycińska, Prof. MD
    • Contact: Agnieszka Tycinska, Prof. MD; Email: agnieszka.tycinska@umb.edu.pl
  • Bydgoszcz, Poland, 85-094
    • Medical University Hospital No.1
    • Contact: Jacek Kubica, Prof. MD
    • Principal Investigator: Jacek Kubica, Prof. MD
  • Bydgoszcz, Poland, 85-168
    • Medical University Hospital No.2
    • Contact: Grzegorz Grześk, Prof. MD
    • Principal Investigator: Grzegorz Grześk, Prof. MD
  • Gdańsk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
    • Contact: Miłosz Jaguszewski, Prof. MD
    • Principal Investigator: Miłosz Jaguszewski, Prof. MD
  • Katowice, Poland, 40-635
    • Górnośląskie Centrum Medyczne Śląskiego Uniwersytetu Medycznego
    • Contact: Wojciech Wojakowski, Prof. MD
    • Principal Investigator: Wojciech Wojakowski, Prof. MD
  • Kraków, Poland, 30-688
    • Szpital Uniwersytecki w Krakowie
    • Contact: Barbara Zawiślak, PhD MD
    • Principal Investigator: Barbara Zawiślak, PhD MD
  • Kraków, Poland, 31-202
    • John Paul II Hospital
    • Contact: Jadwiga Nessler, Prof. MD
    • Principal Investigator: Jadwiga Nessler, Prof. MD
  • Opole, Poland
    • Medical University Hospital
    • Contact: Marek Gierlotka, Prof. MD
    • Principal Investigator: Marek Gierlotka, Prof. MD
  • Poznań, Poland, 61-848
    • University Hospital of Lord's Transfiguration
    • Principal Investigator: Ewa Straburzyńska-Migaj, Prof. MD
    • Contact: Ewa Straburzyńska-Migaj, Prof. MD
  • Warszawa, Poland, 02-097
    • Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
    • Contact: Renata Główczyńska, ScD PhD MD
    • Principal Investigator: Renata Główczyńska, ScD PhD MD
  • Warszawa, Poland, 04-628
    • Cardinal Stefan Wyszyński Institute of Cardiology
    • Contact: Janina Stępińska, Prof. MD
    • Principal Investigator: Janina Stępińska, Prof. MD
  • Wrocław, Poland, 50-556
    • Uniwersytecki Szpital Kliniczny
    • Contact: Robert Zymliński, ScD PhD MD
    • Principal Investigator: Robert Zymliński, ScD PhD MD
  • Zabrze, Poland, 41-800
    • Slaskie Centrum Chorob Serca
    • Contact: Mariusz Gąsior, Prof. MD
    • Principal Investigator: Mariusz Gąsior, Prof. MD
  • Łódź, Poland, 91-347
    • Provincial Specialist Hospital named after Dr. Wł. Biegański
    • Contact: Jarosław Kasprzak, Prof. MD
    • Principal Investigator: Jarosław Kasprzak, Prof. MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; administration of placebo	Other: Placebo; administration of glucose as a continuous iv. infusion, every 4 weeks for 48 weeks (12 infusions in total)
Experimental: Levosimendan; administration of levosimendan	Drug: Levosimendan; administration of levosimendan as a continuous iv. infusion, every 4 weeks for 48 weeks (12 infusions in total)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the number of unplanned hospitalization	unplanned hospitalization due to heart failure decompensation	12 months of follow-up period
the number of deaths	death for any cause	12 months of follow-up period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
total mortality calculations	total mortality for any cause	0-12, 12-18 and 0-18 months
cardiovascular mortality calculations	mortality due to cardiovascular reasons	0-12, 12-18 and 0-18 months
the number of planned hospitalization	planned hospitalization due to heart failure decompensation	0-12, 12-18 and 0-18 months
the number of implantations of mechanical circulatory support	implantation of mechanical circulatory support	0-12, 12-18 and 0-18 months
the number of heart transplantations	heart transplantation	0-12, 12-18 and 0-18 months
quality of life measurements	The Kansas City Cardiomyopathy Questionnaire quality of life questionnaire- an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	0-12, 12-18 and 0-18 months
the six-minute walk test	measures the distance an individual is able to walk over a total of six minutes	0-12, 12-18 and 0-18 months
NTproBNP measurements	measurements of NTproBNP concentrations	0-12, 12-18 and 0-18 months
estimated glomerular filtration rate measurements	measurements of estimated glomerular filtration rate	0-12, 12-18 and 0-18 months
echocardiographic parameters	the change in echocardiographic parameters assessed in transthoracic echocardiographic examination (TTE)	0-12, 12-18 and 0-18 months
patients who returned to levosimendan / placebo infusions	calculations of the percentage of patients who returned to levosimendan / placebo infusions	from the 12th to the 18th months of the study

Collaborators and Investigators

• Sponsor: Medical University of Bialystok
• Collaborators: Institute of Cardiology, Warsaw, Poland; Medical University of Lodz; Poznan University of Medical Sciences; Nicolaus Copernicus University; John Paul II Hospital, Krakow; Medical Research Agency, Poland; University of Opole; Azienda Ospedaliera dei Colli
• Investigators: Study Chair: Agnieszka Tycińska, Prof. MD, Medical University of Bialystok; Principal Investigator: Marek Gierlotka, Prof. MD, University of Opole; Principal Investigator: Jarosław Kasprzak, Prof. MD, Medical University of Łódź; Principal Investigator: Jacek Kubica, Prof. MD, Nicolaus Copernicus University in Toruń; Principal Investigator: Grzegorz Grześk, Prof. MD, Nicolaus Copernicus University in Toruń; Principal Investigator: Jadwiga Nessler, Prof. MD, John Paul II Hospital, Krakow; Principal Investigator: Janina Stępińska, Prof. MD, Cardinal Stefan Wyszyński Institute of Cardiology; Principal Investigator: Ewa Straburzyńska-Migaj, Prof. MD, Poznan University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2021
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: January 4, 2021
• First Submitted That Met QC Criteria: January 10, 2021
• First Posted (Actual): January 12, 2021

Study Record Updates

• Last Update Posted (Actual): January 12, 2021
• Last Update Submitted That Met QC Criteria: January 10, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Systolic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Simendan
• Other Study ID Numbers: 2019/ABM/01/00017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: According to the agreement with the funding institution (Medical Research Agency), the sponsor and research centers must obtain the consent of the funding institution to disclose the clinical trial data.

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