Levosimendan In Ambulatory Heart Failure Patients

Heart Failure With Reduced Ejection Fraction Clinical Trial

— LEIA-HF  

Official title:

Levosimendan In Ambulatory Heart Failure Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04705337
• Other study ID #: 2019/ABM/01/00017
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: January 1, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2021
• Source: Medical University of Bialystok
• Contact: Agnieszka Tycinska, Prof.
• Phone: +48 85 831 8656
• Email: agnieszka.tycinska[@]umb.edu.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 350
• Est. completion date: December 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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

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

Locations

Country	Name	City	State
Poland	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	Górnoslaskie Centrum Medyczne Slaskiego Uniwersytetu Medycznego	Katowice
Poland	John Paul II Hospital	Kraków
Poland	Szpital Uniwersytecki w Krakowie	Kraków
Poland	Provincial Specialist Hospital named after Dr. Wl. Bieganski	Lódz
Poland	Medical University Hospital	Opole
Poland	University Hospital of Lord's Transfiguration	Poznan
Poland	Cardinal Stefan Wyszynski Institute of Cardiology	Warszawa
Poland	Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego	Warszawa
Poland	Uniwersytecki Szpital Kliniczny	Wroclaw
Poland	Slaskie Centrum Chorób Serca	Zabrze

Sponsors (9)

Lead Sponsor	Collaborator
Medical University of Bialystok	Azienda Ospedaliera dei Colli, Institute of Cardiology, Warsaw, Poland, John Paul II Hospital, Krakow, Medical Research Agency, Medical Universtity of Lodz, Nicolaus Copernicus University, Poznan University of Medical Sciences, University of Opole

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the number of unplanned hospitalization	unplanned hospitalization due to heart failure decompensation	12 months of follow-up period
Primary	the number of deaths	death for any cause	12 months of follow-up period
Secondary	total mortality calculations	total mortality for any cause	0-12, 12-18 and 0-18 months
Secondary	cardiovascular mortality calculations	mortality due to cardiovascular reasons	0-12, 12-18 and 0-18 months
Secondary	the number of planned hospitalization	planned hospitalization due to heart failure decompensation	0-12, 12-18 and 0-18 months
Secondary	the number of implantations of mechanical circulatory support	implantation of mechanical circulatory support	0-12, 12-18 and 0-18 months
Secondary	the number of heart transplantations	heart transplantation	0-12, 12-18 and 0-18 months
Secondary	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
Secondary	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
Secondary	NTproBNP measurements	measurements of NTproBNP concentrations	0-12, 12-18 and 0-18 months
Secondary	estimated glomerular filtration rate measurements	measurements of estimated glomerular filtration rate	0-12, 12-18 and 0-18 months
Secondary	echocardiographic parameters	the change in echocardiographic parameters assessed in transthoracic echocardiographic examination (TTE)	0-12, 12-18 and 0-18 months
Secondary	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