Clinical trial NCT04705337: Levosimendan In Ambulatory Heart Failure Patients
Official title: Levosimendan In Ambulatory Heart Failure Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
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
Lead sponsor: Medical University of Bialystok
Sponsor class: OTHER
Collaborators: name: Medical Research Agency, Poland
name: University of Opole
name: Medical University of Lodz
name: Poznan University of Medical Sciences
name: Nicolaus Copernicus University
name: National Institute of Cardiology, Warsaw, Poland
name: Azienda Ospedaliera dei Colli
name: John Paul II Specialist Hospital in Kraków
First posted: 2021-01-12
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: the number of unplanned hospitalization
timeFrame: 12 months of follow-up period
measure: the number of deaths
timeFrame: 12 months of follow-up period
Secondary outcomes:
measure: total mortality calculations
timeFrame: 0-12, 12-18 and 0-18 months
measure: cardiovascular mortality calculations
timeFrame: 0-12, 12-18 and 0-18 months
measure: the number of planned hospitalization
timeFrame: 0-12, 12-18 and 0-18 months
measure: the number of implantations of mechanical circulatory support
timeFrame: 0-12, 12-18 and 0-18 months
measure: the number of heart transplantations
timeFrame: 0-12, 12-18 and 0-18 months
measure: quality of life measurements
timeFrame: 0-12, 12-18 and 0-18 months
measure: the six-minute walk test
timeFrame: 0-12, 12-18 and 0-18 months
measure: NTproBNP measurements
timeFrame: 0-12, 12-18 and 0-18 months
measure: estimated glomerular filtration rate measurements
timeFrame: 0-12, 12-18 and 0-18 months
measure: echocardiographic parameters
timeFrame: 0-12, 12-18 and 0-18 months
measure: patients who returned to levosimendan / placebo infusions
timeFrame: from the 12th to the 18th months of the study
Other outcomes:
Locations:
city: Bialystok
country: Poland
facility: Medical University of Bialystok Clinical Hospital
city: Bydgoszcz
country: Poland
facility: Medical University Hospital No.1
city: Bydgoszcz
country: Poland
facility: Medical University Hospital No.2
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Katowice
country: Poland
facility: Górnośląskie Centrum Medyczne Śląskiego Uniwersytetu Medycznego
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie
city: Kraków
country: Poland
facility: John Paul II Hospital
city: Opole
country: Poland
facility: Medical University Hospital
city: Poznań
country: Poland
facility: University Hospital of Lord's Transfiguration
city: Warszawa
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
city: Warszawa
country: Poland
facility: Cardinal Stefan Wyszyński Institute of Cardiology
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny
city: Zabrze
country: Poland
facility: Śląskie Centrum Chorób Serca
city: Łódź
country: Poland
facility: Provincial Specialist Hospital named after Dr. Wł. Biegański
Study officials:
affiliation: Medical University of Bialystok
name: Agnieszka Tycińska, Prof. MD
role: STUDY_CHAIR
affiliation: University of Opole
name: Marek Gierlotka, Prof. MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of Łódź
name: Jarosław Kasprzak, Prof. MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nicolaus Copernicus University in Toruń
name: Jacek Kubica, Prof. MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nicolaus Copernicus University in Toruń
name: Grzegorz Grześk, Prof. MD
role: PRINCIPAL_INVESTIGATOR
affiliation: John Paul II Hospital, Krakow
name: Jadwiga Nessler, Prof. MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cardinal Stefan Wyszyński Institute of Cardiology
name: Janina Stępińska, Prof. MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Poznan University of Medical Sciences
name: Ewa Straburzyńska-Migaj, Prof. MD
role: PRINCIPAL_INVESTIGATOR
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