Heart failure with reduced ejection fraction MedDRA version: 17.1 Level: LLT Classification code 10024106 Term: Left heart failure System Organ Class: 100000004849
Conditions
Interventions
Product Name: CXL-1427
Product Code: CXL-1427
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: CXL-1427
Other descriptive name: N-Hydr
Sponsors
Cardioxyl Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be = 18 and =85 years of age; 2. 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; 3. 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; 4. 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.] 5. 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.] 6. 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); 7. 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; 8. Have a body weight of at least 50kg (110 pounds), but not more than 125kg (275 pounds), and have a body mass index (BMI) =65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
Exclusion criteria: 1. Have a heart rate 110 beats per min. (bpm) at baseline; 2. Have a screening OR baseline systolic blood pressure (SBP) of: >150mmHg; 1.8cm) or uncorrected severe valvular disease as defined by AHA/ACC/ESC criteria; 5. Have been treated with dopamine, dobutamine, enoximone, nesiritide, nitroglycerine or nitroprusside within 4 hrs, or with levosimendan, amrinone or milrinone within 8 hrs, 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-hr study drug infusion; 6. Be receiving concomitant parenteral therapy with any antiarrhythmic drugs (oral therapy is allowed); 7. Be in atrial fibrillation/flutter with an uncontrolled rate (=100bpm) at the time of randomization; 8. Have non-sustained ventricular tachycardia (NSVT) of 10 beats or more during any bedside monitoring within 2 hrs prior to randomization, or have excessive premature ventricular contractions (PVCs) or complex multifocal ventricular ectopy exceeding 10 beats per minute on a 2-min. rhythm strip taken within 2 hrs prior to randomization; 9. 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 hrs before the start of the study drug infusion, until after the completion of the study drug infusion; 10. Have a history of sudden cardiac death/resuscitation or other appropriate ICD firing within the past 1 year. (Inappropriate ICD firings are not exclusionary); 11. Be hospitalized with acute coronary syndrome or acute myocardial infarction during the previous 90 days prior to randomization; 12. Have a history of a cerebral vascular accident (CVA or stroke) or of a transient ischemic attack (TIA) within 6 months prior to randomization; 13. Have a digoxin level above 1ng/ml (1.281nmol/L) within 8 hrs before initiation of the study drug infusion; 14. Have persistent abnormal serum electrolytes at baseline, as defined by: a Na+ concentration 145 mEq/L, or a K+ or Mg2+ concentration outside the normal range (according to the local lab); 15. Have an ALT or AST >3 times the upper normal limit or a hemoglobin 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 initiatio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Evaluate the safety and tolerability of 6-hour infusions of CXL-1427 in patients with systolic congestive heart failure. • Evaluate the effects of 6-hour intravenous infusions of CXL-1427 on pulmonary capillary wedge pressure (PCWP), pulmonary artery diastolic pressure (PAD) and cardiac index (CI), measured by an indwelling PA catheter. ;Secondary Objective: • Evaluate the effects of CXL-1427 on other hemodynamic parameters [e.g., right atrial pressure (RAP), pulmonary artery pressures (systolic and mean), peripheral arterial systolic and diastolic blood pressures (SBP and DBP, by sphygmomanometry); calculated mean peripheral arterial blood pressure (MAP); and heart rate (HR)]. • Assess plasma concentrations of CXL-1427 and its metabolites in heart failure patients. • Evaluate dose/pharmacodynamic (PD) effect and pharmacokinetic (PK)/PD effect relationships for the observed effects on central and peripheral hemodynamic parameters. ;Primary end point(s): - Safety and tolerability - Cardiac Index and PCWP (or PAD) via PA line ;Timepoint(s) of evaluation of this end point: Safety assessments will be completed 24 hours after the study drug infusion is initiated. Subsequent assessments will be made at a follow-up visit between Study Day 8-12, and with/at a finla follwo-up phone call/visit between Study Day 32-36. Invassive assessments of Cardiac Index, PCWP and PAD will be obtained at screening (= 4 hours prior to study drug); baseline (= 30 minutes prior to study drug); during the 6-hour infusion of study drug at Hours 2, 4 and 6; 2 hours after the study drug infusion is completed, i.e., at Hour 8. If early termination a full set of hemodynamic tracings should be obtained just prior to cessation of infusion, and 2 hours after the termination of infusion. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Right atrial pressure, pulmonary artery systolic and mean pressures via PA line - Peripheral arterial systolic and diastolic blood pressures - Heart rate;Timepoint(s) of evaluation of this end point: Secondary central hemodynamic endpoints will be assessed concurrently with the primary central hemodynamic endpoints. Peripheral blood pressure and heart rate will be assessed at multiple time points, including every 30 minutes during the 6-hour infusion of study drug and until 2 hours after the study drug infusion is completed. | — |
Countries
Germany, Jordan, Poland, Russian Federation, United States
Contacts
Public ContactShiYin Foo, Chief Medical Officer
Cardioxyl Pharmaceuticals, Inc.
Outcome results
None listed