chronic heart failure with reduced ejection fraction (LVEF equal or below 35%)
Conditions
Interventions
Product Name: BAY 1067197 hydrochloride film coated tablet 5 mg
Product Code: BAY 1067197 hydrochloride film coated tablet 5 mg
Pharmaceutical Form: Coated tablet
Sponsors
Bayer AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men or women aged 18 years and older 2. Diagnosis of chronic heart failure (CHF), NYHA class II-IV, LVEF = 35% assessed by any imaging modality (e.g. echocardiography, cardiac magnetic resonance [CMR], cine levocardiography) within 6 months prior to run-in: if several values are available the last assessment of EF should be = 35%. 3. One of the following (or both), a) Worsening CHF requiring hospitalization or an unscheduled outpatient visit in the last 3 months, both requiring initiation or intensification of heart failure therapy and with either: o BNP = 100 pg/mL or NT-proBNP =400 pg/mL (sinus rhythm) or o BNP = 300 pg/mL or NT-proBNP =1200 pg/mL (atrial fibrillation) AND/OR b) at any time in the past 4 weeks one of: o BNP = 300 pg/mL or NT-proBNP = 1200 pg/mL (sinus rhythm) o BNP = 600 pg/mL or NT-proBNP = 2400 pg/mL (atrial fibrillation) For patients on treatment with angiotensin receptor-neprilysin inhibitors (ARNIs), e.g. Entresto only NT-proBNP values can be used to assess eligibility. 4. Written informed consent before any study-specific procedure Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 96 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 288
Exclusion criteria
Exclusion criteria: 1. Acute de-novo heart failure 2. Requirement of any of the following 48 hours prior to randomization: IV vasodilating drugs (e.g. nitrates, nitroprusside) - IV natriuretic peptides (e.g. nesiritide, carperitide) - IV positive inotropic agents - IV diuretics - IV antibiotics - Mechanical support (e.g. intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) 3. Any cause of chronic heart failure other than ischemic cardiomyopathy and idiopathic dilated cardiomyopathy 4. Known clinically significant persistent coronary ischemia based on medical history, preexisting or current exercise testing 5. Occurrence of any of the following within 3 months prior to randomization: o Myocardial infarction o Hospitalization for unstable angina o Stroke or TIA o Coronary artery bypass graft (CABG) o Percutaneous coronary intervention (PCI) o Implantation of a cardiac resynchronization therapy device (CRTD) o Carotid angioplasty 6. PCI, CABG or implantation of a CRTD planned between randomization and end of study 7. Sustained* systolic blood pressure = 90 mmHg and / or signs and symptoms of hypotension prior to randomization 8. Sustained* systolic blood pressure = 160 mmHg 9. Sustained* bradycardia with heart rate 100 beats/minute prior to randomization 10. Known clinically relevant ventricular arrhythmias (sustained ventricular tachycardia, ventricular flutter or fibrillation) within 3 months prior to consent based on either medical history or ICD-testing results (if applicable) 11. Clinically relevant permanent or intermittent AV-block > grade II in patients without a permanent pacemaker or ICD / CRT device 12. Severe valvular disease with indicated or planned valve repair / replacement 13. Listing for heart transplantation and / or anticipated implantation of a ventricular assist device 14. Severe pulmonary disease with any of the following: o Requirement of continuous (home) oxygen or o History of COPD = GOLD III or o Use of systemic corticosteroids 15. Asthma bronchiale with any of the following: o Symptoms not well-controlled within the past 6 months or o Ever intubated or in an intensive care unit for asthma 16. Anemia with hemoglobin 40 kg/m2 at randomization or a history of poor quality LVEF measurement by echocardiography 18. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 calculated by Modification of Diet in Renal Disease (MDRD) form
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Find the optimal dose of neladenoson bialanate for the Phase III trial by detecting and characterizing a significant dose-response relationship in the two primary efficacy endpoints, absolute change from baseline in LVEF and log-transformed NT-proBNP at 20 weeks, in patients with chronic heart failure with reduced ejection fraction (HFrEF), and by characterizing the safety, tolerability and pharmacodynamic effects of the compound when given in addition to standard therapy for HFrEF.;Secondary Objective: An exploratory objective is to further investigate the drug and the pathomechanism of heart failure by evaluating pharmacokinetic parameters and blood and urine biomarkers.; Primary end point(s): • Absolute change from baseline in left ventricular ejection fraction (LVEF; %) after 20 weeks of treatment measured by echocardiography • Absolute change from baseline in log-transformed NT-proBNP (pg/mL) after 20 weeks, i.e., log-transformed NT-proBNP at week 20 minus log-transformed NT-proBNP at baseline. ;Timepoint(s) of evaluation of this end point: at the end of the study, no formal interim analysis is planned | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Key echocardiographic parameters, measured values and absolute change from baseline at 20 weeks: o Left ventricular end-systolic volume (LVESV; mL) o Left ventricular end-diastolic volume (LVEDV; mL) • High sensitivity troponin T (hs-TNT; ng/L), measured values (log transformed) and absolute?/?relative change from baseline at 20 weeks as a biomarker of myocardial injury • CV mortality, HF hospitalization and urgent visits for HF as clinical outcome ;Timepoint(s) of evaluation of this end point: at the end of the study, no formal interim analysis is planned | — |
Countries
Belgium, Bulgaria, Germany, Greece, Israel, Italy, Japan, Netherlands, Poland, Spain, United States
Contacts
Public ContactBayer Clinical Trials Contact
Bayer AG
Outcome results
None listed