A Dose Ranging Phase IIa Study of 6 Hour Intravenous Dosages of CXL-1427 in Patients Hospitalized With Heart Failure

Inclusion Criteria: * Inclusion Criteria -In order to be eligible for study participation, a patient MUST: * Be ≥ 18 and ≤ 85 years of age; * Have a left ventricular ejection fraction (LVEF) ≤40%, as assessed by echocardiography, a multigated acquisition (MUGA) scan or magnetic resonance imaging (MRI) within 3 months prior to or during the current hospitalization; * Be hospitalized with a primary heart failure or heart failure-related reason, e.g., acute decompensation of heart failure, transplant evaluation, hemodynamic optimization prior to ambulatory inotropes or left ventricular assist device placement; * Have an indwelling pulmonary artery (PA) catheter in place for assessment of central hemodynamic parameters; \[Note: The indwelling catheter may already be in place for medically-indicated reasons, OR be placed for the primary purpose of monitoring the hemodynamic effects of the study drug. If the pulmonary artery catheter is to be placed for the sole purpose of monitoring the hemodynamic effect of the study drug, the patient must have a cardiac index (CI) ≤ 2.2L/min•m2 as measured by a non-invasive cardiac output monitor (NICaS device) ≤6 hours prior to placement of the catheter. In this setting, Exclusion Criteria 3 below also applies.\] * Have a Fick and/or thermodilution determination of cardiac index ≤2.5L/min•m2 at screening, i.e., ≤4 hours before the intended start of the study drug infusion; \[Note: For determinations of CI using the thermodilution method, a mean of three consecutive values measured approximately 5 minutes apart, none of which differs from the mean value by more than 15%, should be used.\] * Have a screening and baseline PCWP (or PAD, if a PCWP waveform cannot be reliably obtained) of ≥20 mmHg if systolic blood pressure is ≥100mmHg OR ≥22mmHg if systolic blood pressure is between 95-99mmHg (inclusive); * Be considered sufficiently stable to be expected not to require administration of any IV or oral vasoactive medications, including diuretics, for at least \~10 hours, i.e., from 4 hours before performing baseline hemodynamic assessments until after the completion of the 6-hour study drug infusion; * Have a body weight of at least 50kg (110 pounds), but not more than 125kg (275 pounds), and have a body mass index (BMI) \<40kg/m2; * Have adequate peripheral forearm vein access or an available central line port for administration of study drug; * Be capable of understanding the nature of the trial; be willing and able to comply with the inpatient and outpatient study protocol requirements for the duration of the study (screening period, treatment period, and 30-day post-infusion follow-up period); and be willing to participate in the study, as documented by written informed consent. Exclusion Criteria- - In order to be eligible for study participation, a patient MUST NOT: * Have a heart rate \<50 or \>110 beats per minute (bpm) at baseline; * Have a screening OR baseline systolic blood pressure (SBP) of \>150mmHg or \<100mmHg, if PCWP ≥ 20mmHg, but \<22mmHg OR \<95mmHg, if PCWP ≥ 22mmHg; * Have tricuspid or pulmonary valve prosthesis or endocarditis, right heart mass, a history of pneumothorax or hemothorax, a bleeding diathesis that would preclude placement of a PAL, or a history of complications from previous pulmonary artery catheter placement, when a pulmonary artery catheter is to be placed solely for the purposes of monitoring the hemodynamic effects of the study drug; In this setting, patients with multiple intracardiac leads and/or left bundle branch block should have such elective pulmonary artery catheter placement performed under radiologic guidance by experienced personnel, e.g. in the cardiac catheterization laboratory. \[Note: Other pertinent history, such as trauma, vascular injury or previous surgery should guide selection of the vessel for PAL placement.\] * Have a primary HF etiology attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic cardiomyopathy (as defined by any wall thickness \> 1.8cm) or uncorrected severe valvular disease as defined by AHA/ACC/ESC criteria; * Have been treated with dopamine, dobutamine, enoximone, nesiritide, nitroglycerine or nitroprusside within 4 hours, or with levosimendan, amrinone or milrinone within 8 hours, prior to performing baseline hemodynamic assessments, or have an anticipated need to be treated with any of these agents before the completion of the 6-hour study drug infusion; * Be receiving concomitant parenteral therapy with any antiarrhythmic drugs (oral therapy is allowed); * Be in atrial fibrillation/flutter with an uncontrolled rate (≥100bpm) at the time of randomization; \[Note: Patients with a history of A-fib/flutter are eligible, if heart rate is controlled with a ventricular rate not exceeding 100bpm.\] * Have non-sustained ventricular tachycardia (NSVT) of 10 beats or more during any bedside monitoring within 2 hours prior to randomization, or have excessive premature ventricular contractions (PVCs) or complex multifocal ventricular ectopy exceeding 10 beats per minute on a 2-minute rhythm strip taken within 2 hours prior to randomization; * Require, or be expected to require, any alteration of settings to an implantable cardioverter-defibrillator (ICD), single chamber or biventricular pacemaker, if applicable, from 2 hours before the intended start of the study drug infusion, until after the completion of the study drug infusion; * Have a history of sudden cardiac death/resuscitation or other appropriate ICD firing within the past 1 year. (Inappropriate ICD firings are not exclusionary); * Be hospitalized with acute coronary syndrome or acute myocardial infarction during the previous 90 days prior to randomization; * Have a history of a cerebral vascular accident (CVA or stroke) or of a transient ischemic attack (TIA) within 6 months prior to randomization; * Have a digoxin level above 1ng/ml (1.281nmol/L) within 8 hours before initiation of the study drug infusion; * Have persistent abnormal serum electrolytes at baseline, as defined by: a Na+ concentration \<130 or \>145 mEq/L, or a K+ or Mg2+ concentration outside the normal range (according to the local laboratory); \[Note: Any observed electrolyte abnormalities during screening or earlier should be corrected by electrolyte supplementation and within normal acceptable concentrations should be confirmed prior to dosing. Any serum electrolyte abnormalities with associated clinical instability within 8 hours before initiation of the study drug infusion is exclusionary.\] * Have an ALT or AST \>3 times the upper normal limit or a hemoglobin \<10g/dl (100g/L) within 8 hours before initiation of the study drug infusion; * Have a serum creatinine \>2.5mg/dl (221µmol/L) or severe renal insufficiency \[based on any standard limit and equation employed by the local lab, such as a GFR \< 30mL/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) equation\] within 8 hours before initiation of the study drug infusion; * Have taken an oral phosphodiesterase type 5 inhibitor (PDE5) inhibitor within 96 hours before initiation of the study drug infusion; * If female, be pregnant or of child-bearing potential (i.e., female patients must be post-menopausal or surgically sterilized); * Be receiving a drug which is expected to possess a potential for a clinically significant pharmacokinetic interaction with CXL-1427, as defined in the CXL-1427 Investigator's Brochure; * Be the recipient of a myocardial restraint device or flap; * Have an anticipated survival of less than 90 days, for any reason; * Have received an investigational drug, device or biologic product within 30 days (or if longer, 5 half-lives for a drug or biologic agent) prior to randomization, or be planning to receive an investigational agent at any time throughout the full duration of the study until at least 30 days after discontinuation of study drug; * Have any other clinically significant laboratory abnormality, medical condition or social circumstance that, in the investigator's opinion, makes it inappropriate for the patient to participate in this clinical trial.