Levosimendan In Ambulatory Heart Failure Patients

Phase 4

Not yet recruiting

• Conditions: 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
• Interventions: Other: Placebo; Drug: Levosimendan

• Registration Number: NCT04705337
• Lead Sponsor: Medical University of Bialystok

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.

Study Timeline

• Status Verified: 2021-01
• Study Start: 2021-01-01
• Study First Submitted: 2021-01-04
• Study First Submitted QC: 2021-01-10
• Last Update Submitted: 2021-01-10
• Study First Posted: 2021-01-12
• Last Update Posted: 2021-01-12
• Primary Completion: 2024-06-30
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 350

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	administration of placebo
Levosimendan	Levosimendan	administration of levosimendan

Primary Outcome Measures

Name	Time	Method
the number of deaths	12 months of follow-up period	death for any cause
the number of unplanned hospitalization	12 months of follow-up period	unplanned hospitalization due to heart failure decompensation

Secondary Outcome Measures

Name	Time	Method
the number of planned hospitalization	0-12, 12-18 and 0-18 months	planned hospitalization due to heart failure decompensation
the six-minute walk test	0-12, 12-18 and 0-18 months	measures the distance an individual is able to walk over a total of six minutes
cardiovascular mortality calculations	0-12, 12-18 and 0-18 months	mortality due to cardiovascular reasons
estimated glomerular filtration rate measurements	0-12, 12-18 and 0-18 months	measurements of estimated glomerular filtration rate
the number of heart transplantations	0-12, 12-18 and 0-18 months	heart transplantation
total mortality calculations	0-12, 12-18 and 0-18 months	total mortality for any cause
the number of implantations of mechanical circulatory support	0-12, 12-18 and 0-18 months	implantation of mechanical circulatory support
NTproBNP measurements	0-12, 12-18 and 0-18 months	measurements of NTproBNP concentrations
quality of life measurements	0-12, 12-18 and 0-18 months	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.
echocardiographic parameters	0-12, 12-18 and 0-18 months	the change in echocardiographic parameters assessed in transthoracic echocardiographic examination (TTE)
patients who returned to levosimendan / placebo infusions	from the 12th to the 18th months of the study	calculations of the percentage of patients who returned to levosimendan / placebo infusions

Trial Locations

Locations (14)

University Hospital of Lord's Transfiguration; 🇵🇱 Poznań, Poland

Cardinal Stefan Wyszyński Institute of Cardiology; 🇵🇱 Warszawa, Poland

Medical University Hospital No.2; 🇵🇱 Bydgoszcz, Poland

Uniwersyteckie Centrum Kliniczne; 🇵🇱 Gdańsk, Poland

Górnośląskie Centrum Medyczne Śląskiego Uniwersytetu Medycznego; 🇵🇱 Katowice, Poland

Szpital Uniwersytecki w Krakowie; 🇵🇱 Kraków, Poland

John Paul II Hospital; 🇵🇱 Kraków, Poland

Medical University Hospital; 🇵🇱 Opole, Poland

Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego; 🇵🇱 Warszawa, Poland

Provincial Specialist Hospital named after Dr. Wł. Biegański; 🇵🇱 Łódź, Poland

Uniwersytecki Szpital Kliniczny; 🇵🇱 Wrocław, Poland

Śląskie Centrum Chorób Serca; 🇵🇱 Zabrze, Poland

Medical University of Bialystok Clinical Hospital; 🇵🇱 Bialystok, Poland

Medical University Hospital No.1; 🇵🇱 Bydgoszcz, Poland