a phase 2 study to evaluate the cardiac and renal effects of short term treatment with elamipretide in patients hospitalized with congestion due to heart failure

Conditions: Heart Failure

Summary: this is a phase 2 randomized, double-blind, placebo-controlled study to evaluate the cardiac and renal effects of short term treatment with elamipretide in patients hospitalized with congestion due to heart failure


Eligibility criteria:
inclusion criteria: * a history of chronic heart failure for at least 1 month * treated with ≥40 mg/day of furosemide or bumetanide ≥1 mg/day or torasemide ≥10 mg/day for at least 1 month * in-hospital observation/admission and treatment for ≤72 hours and primary cause for admission is heart failure with persistent congestion in the opinion of the investigator (i.e. at least +2 pitting oedema and/or an estimated 8 kg gain in weight over baseline over the past 4 weeks) requiring intravenous loop diuretic therapy * sufficiently severe oedema to justify treatment by an intravenous infusion of furosemide of 10 mg/hour for at least 48 hours * systolic blood pressure \>90 mmhg and considered to be haemodynamically stable, in the opinion of the investigator * history of left ventricular ejection fraction (lvef) ≤40% confirmed in the last 18 months * nt-probnp \>1500 pg/ml or bnp \>500 pg/ml * an egfr of \>30 ml/min/1.73 m2 using the egfr (ml/min/1.73 m2) = 175 x (scr)-1.154 x (age)-0.203 x (0.742 if female) x (1.212 if african american) exclusion criteria: * acute coronary syndrome, stroke, or transient ischemic attack (tia), coronary or peripheral revascularization procedures, valve procedures, or any major surgical procedure within the previous 6 weeks * invasive cardiac investigation and/or treatment (i.e. coronary angiography, percutaneous coronary intervention \[pci\] or surgery) or other surgical procedure planned in the next 4 weeks * use of intravenous radiographic contrast agent within 72 hours prior to screening or planned use during the study * severe, in the investigators opinion, uncorrected valve disease or congenital heart disease as the cause for cardiac decompensation * acute mechanical cause of decompensated heart failure such as papillary muscle rupture * obstructive or infiltrative cardiomyopathy (e.g. amyloid, sarcoid, etc), suspected acute myocarditis, or heart failure related to an untreated metabolic condition (e.g. haemochromatosis) * second or third degree heart block unless the subject has a ventricular pacemaker * atrial fibrillation/flutter with sustained ventricular response of \>130 bpm * placement of a ventricular resynchronization device within the previous 6 weeks * treatment or planned treatment with intravenous inotropic agents other than digoxin at any time on this admission * receipt of intravenous vasodilator therapy ≤ 6 hours prior to randomization * the presence of any mechanical assist device or listed for or a history of a heart transplant * severe respiratory disease or anticipated need for mechanical respiratory support (i.e. mechanical ventilation) * anuric in the previous 24 hours * haemoglobin \<9 g/dl at screening or planned blood transfusions in the next 30 days * serum potassium \>5.5 meq/l * marked proteinuria suggestive of nephrotic syndrome * estimated gfr (egfr) as per mdrd equation \<30 ml/min * serum albumin of \< 2.8 g/dl * liver enzymes (alanine aminotransferase \[alt\] and/or aspartate aminotransferase \[ast\]) elevation \>5 times the upper limit of normal (uln) * total bilirubin \>2.0 times uln in the absence of gilbert's syndrome * current or planned ultrafiltration, paracentesis, haemofiltration or dialysis

Keywords: heart failure diuresis dropsy congestion elamipretide mtp-131 bendavia™