A study assessing the Safety, Tolerability and Hemodynamic Effects of a Continuous 6-Hour Intravenous Infusion of CXL-1427 in Hospitalized Patients with Systolic Heart Failure
- Conditions
- Heart failure with reduced ejection fractionMedDRA version: 17.1Level: LLTClassification code 10024106Term: Left heart failureSystem Organ Class: 100000004849Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2014-000771-24-DE
- Lead Sponsor
- Cardioxyl Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 48
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) <40kg/m2;
9. Have adequate peripheral forearm vein access or an available central line port for administration of study drug;
10. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28
1. Have a heart rate <50 or >110 beats per min. (bpm) at baseline;
2. Have a screening OR baseline systolic blood pressure (SBP) of: >150mmHg; <100mmHg, if PCWP = 20mmHg, but <22mmHg OR <95mmHg, if PCWP = 22mmHg;
3. 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 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.
4. 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;
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 <130 or >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 <10g/dl (100g/L) within 8 hrs before initiation of the study drug infusion;
16. 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 initiatio
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method