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
Conditions
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.
Interventions
DRUGLevosimendan
administration of levosimendan as a continuous iv. infusion, every 4 weeks for 48 weeks (12 infusions in total)
OTHERPlacebo
administration of glucose as a continuous iv. infusion, every 4 weeks for 48 weeks (12 infusions in total)
Sponsors
Medical Research Agency, Poland
University of Opole
Medical University of Lodz
Poznan University of Medical Sciences
Nicolaus Copernicus University
National Institute of Cardiology, Warsaw, Poland
Azienda Ospedaliera dei Colli
John Paul II Hospital, Krakow
Medical University of Bialystok
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the number of unplanned hospitalization | 12 months of follow-up period | unplanned hospitalization due to heart failure decompensation |
| the number of deaths | 12 months of follow-up period | death for any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the number of planned hospitalization | 0-12, 12-18 and 0-18 months | planned hospitalization due to heart failure decompensation |
| the number of implantations of mechanical circulatory support | 0-12, 12-18 and 0-18 months | implantation of mechanical circulatory support |
| the number of heart transplantations | 0-12, 12-18 and 0-18 months | heart transplantation |
| 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. |
| total mortality calculations | 0-12, 12-18 and 0-18 months | total mortality for any cause |
| NTproBNP measurements | 0-12, 12-18 and 0-18 months | measurements of NTproBNP concentrations |
| estimated glomerular filtration rate measurements | 0-12, 12-18 and 0-18 months | measurements of estimated glomerular filtration rate |
| echocardiographic parameters | 0-12, 12-18 and 0-18 months | the change in numerous echocardiographic parameters with different units assessed in each patient 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 |
| 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 |
Countries
Poland
Outcome results
None listed