Clinical trial NCT02914665 (phase 2, status: completed)
Conditions: heart failure
ICD codes: I50.814, I09.81, I50.82, I50.89, I50.9, T86.22, I11.0
Drugs: elamipretide, placebo
SMILES: CC1=CC(O)=CC(C)=C1C[C@H](NC(=O)[C@H](N)CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(N)=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
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