Patients being admitted to hospital for acute heart failure (AHFS) with volume overload and renal impairment. MedDRA version: 9.1 Level: LLT Classification code 10000803 Term: Acute heart failure
Conditions
Interventions
Product Name: KW-3902 Injectable Emulsion
Product Code: KW-3902IV
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: Not available
Sponsors
NovaCardia Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to provide written informed consent or a legally authorized representative is able to provide written informed consent 2. Male or female 18 years of age or greater 3. History of heart failure of at least 14 days duration for which diuretic therapy has been prescribed 4. Hospitalized for AHFS requiring IV diuretic therapy. AHFS is defined as dyspnea at rest or with minimal exertion and signs of fluid overload manifested by at least one of the following at time of randomization: • JVP >8 cm, or • Pulmonary rales =1/3 up the lung fields, not clearing with cough, or • =2+ peripheral edema, or pre-sacral edema 5. Eligible for start of study drug infusion within 24 hours from presentation to the hospital, including the emergency department 6. Anticipated need for IV furosemide =40 mg/day (or equivalent dose of IV loop diuretic) for at least 24 hours after start of study drug 7. Impaired renal function defined as a creatinine clearance on admission between 20-80 mL/min using the Cockcroft-Gault equation for estimating creatinine clearance (corrected for height in edematous or obese subjects =100 kg) 8. Systolic blood pressure =95 mmHg (subjects with a systolic blood pressure of 90 –94 mmHg at randomization may be included if their usual systolic blood pressure measurements are consistently within this range while clinically stable) 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Pregnant or breast feeding women. Women of child bearing potential must have a negative urine or serum pregnancy test prior to enrollment. 2. Acute contrast induced nephropathy 3. Temperature >38°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment 4. Serum potassium 120 beats per minute) 13. Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy. This criterion does not include restrictive patterns seen on Doppler. 14. Known hepatic impairment (total bilirubin >3 mg/dL, albumin 160 mmHg at randomization 19. Inability to follow instructions or comply with follow-up procedures 20. Allergy to soybean oil or eggs 21. History of seizure (except febrile seizure) 22. Stroke within 2 years 23. History of or current brain tumor of any etiology 24. Brain surgery within 2 years 25. Encephalitis/meningitis within 2 years 26. History of penetrating head trauma 27. Closed head injury with loss of consciousness (LOC) over 30 minutes within 2 years 28. History of, or at risk for, alcohol withdrawal seizures 29. Advanced Alzheimer’s disease 30. Advanced multiple sclerosis 31. Hgb <8 g/dL, Hct <25%, or the need for a blood transfusion 32. Previous exposure to KW-3902
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this study is to evaluate the effect of KW-3902IV in addition to intravenous (IV) loop diuretic therapy on heart failure signs and symptoms and renal function in subjects hospitalised with AHFS, volume overload, and renal impairment.;Secondary Objective: The secondary objectives of this study are to evaluate the safety of KW-3902IV in subjects hospitalised with AHFS, volume overload and renal impairment and to estimate and compare within trial medical resource utilization and direct medical costs between patients treated with KW-3902IV versus placebo.; Primary end point(s): A three category, ordered outcome of treatment success, patient unchanged, or treatment failure based on the following definitions: • Treatment success (determined at 24 and 48 hours after the start of study drug [Day 2 and 3] or the day of discharge if earlier): o Dyspnea reported by the patient using a 7-point Likert scale as moderately or markedly better compared to study start, AND o Not a treatment failure • Patient Unchanged: Neither treatment success or treatment failure • Treatment failure (includes any 1 of the following criteria): o Death or readmission for heart failure any time through Day 7; OR o Worsening symptoms and/or signs of heart failure occurring >24 hours after the start of study drug to Day 7 or discharge, whichever occurs first, such that there is a need for any one of the following types of “rescue therapy”: an increase in the dose or reinstitution of IV loop diuretic therapy, or initiation of oral metolazone or IV chlorothiazide as accompanying therapy to loop diuretics or initiation of ultrafiltration or initiation of IV positive inotropes, vasopressors, or IV vasodilators or init | — |
Countries
Czech Republic, Germany, Hungary, Italy, Netherlands, Spain, United Kingdom
Outcome results
None listed