a trial to study bay1753011 in patients with congestive heart failure

Conditions: Heart Failure (HF)

Summary: to assess the efficacy of 30 mg of bay1753011, with or without furosemide, versus furosemide alone in patients with heart failure and objective evidence of congestion.


Eligibility criteria:
inclusion criteria: * history of chf on individually optimized treatment with hf medications unless contraindicated or not tolerated, for at least 12 weeks prior to index hospitalization and in accordance with international guidelines. * subjects admitted to the hospital with a primary diagnosis of decompensated hf including symptoms and signs of fluid overload requiring iv diuretic therapy in the emergency room (er) or any time between day 1-3 of hospital admission (index hospitalization). * subjects on an average/usual total daily dose of loop diuretic ≥ 40 mg of furosemide or equivalent, within 4 weeks prior to index hospitalization. * at least one of the following 5 parameters any day between 3-7 of index hospitalization (screening period) * natriuretic peptides brain natriuretic peptide/n-terminal prohormone of brain natriuretic peptide (bnp/nt-probnp): * drop in bnp or nt-probnp ≤ 30% from admission values (if measured during index hospitalization) or * bnp ≥ 500 pg/ml or nt-probnp ≥ 1800 pg/ml at screening (day 3 to 7 of index hospitalization) * body weight (bw) loss \<0.4 kg per 40 mg furosemide at day 4 of index hospitalization * composite congestion score (ccs) ≥ 3 * hypervolemic hyponatremia defined as serum sodium \< 136 mmol/l * in hospital worsening renal function defined as increased serum creatinine ≥ 0.3 mg/dl compared to index hospitalization admission values and at least one the following * jugular venous pressure (jvp) ≥ 10 cm on physical examination * inferior vena cava (ivc) diameter \> 21 mm * ivc collapse with sniff \< 50% * at least 2+ peripheral edema or pulmonary edema or pleural effusion on chest x-ray or clinical exam exclusion criteria * active or history of acute inflammatory heart disease, within 3 months prior to screening, e.g., acute myocarditis * acute coronary syndrome, including unstable angina, non-st segment elevation myocardial infarction (nstemi) or st segment elevation myocardial infarction (stemi), or major cardiovascular (cv) surgery including coronary artery bypass graft (cabg), percutaneous coronary intervention (pci) within 3 months prior to screening * any primary cause of hf scheduled for surgery or interventional therapy (e.g., tavi), e.g., valve disease such as severe aortic stenosis or mitral valve regurgitation * requirement of mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) or ultrafiltration/hemodialysis * estimated glomerular filtration rate of \< 30 ml/min/1.73 m\*2 determined by the modified diet and renal disease equation at screening; reassessments allowed as clinically needed * serum potassium ≥ 5.5 mmol/l or ≤ 3.3 mmol/l at screening; reassessments allowed as clinically needed * serum sodium ≥ 146 mmol/l or ≤ 130 mmol/l at screening; reassessments allowed as clinically needed * concomitant treatment with potassium-sparing diuretic (with the exception of mineralocorticoid- receptor antagonist (mra) that cannot be stopped prior to randomization and for the duration of the treatment period.

Keywords: chronic heart failure (chf) heart failure with reduced ejection fraction (hfref) heart failure with preserved ejection fraction (hfpef) heart failure with mid-range ejection fraction (hfmref)