Patients being admitted to hospital with heart failure and volume overload requiring IV therapy after experiencing worsening of renal function. MedDRA version: 9.1 Level: LLT Classification code 10000803 Term: Acute heart failure
Conditions
Interventions
Product Name: KW-3902 Injectable Emulsion
Product Code: KW-3902 IV
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: Not available
CAS Number: 136199-02-5
Current Sponsor code: KW-3902
Sponsors
NovaCardia Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to provide written informed consent, or a legally authorised representative is able to provide written informed consent. 2. Male or female 18 years of age or greater. 3. Dyspnea at rest or with minimal exertion at randomisation. 4. Fluid overload as manifested by at least one of the following present at randomization: JVP >10 cm OR Pulmonary rales =1/3 up the lung fields, not clearing with cough, OR =2+ peripheral or pre-sacral edema 5. Estimated creatinine clearance (CrCl) between 20–60 mL/min using the Cockcroft-Gault equation (corrected for height in edematous subjects =100 kg) based on a serum creatinine (SCr) value drawn within approximately 6 hours of randomization 6. Worsening renal function as manifested by one of the following present at randomization: • An increase in SCr of at least 25% and at least 0.3 mg/dL from the time of initial presentation for this hospitalization in patients hospitalized with heart failure requiring IV diuretic therapy, OR • A documented increase in SCr over the preceding 30 days prior to randomization of at least 40% and at least 0.3 mg/dL in patients being admitted for heart failure requiring IV therapy (these patients must be randomized within 24 hours of admission) 7. Anticipated need for IV diuretic treatment for at least 48 hours after the start of study drug 8. BNP >500 pg/mL or NT-pro-BNP >2000 pg/mL 9. Systolic blood pressure =90 mmHg at randomization. Subjects with systolic blood pressure of 85-89 mmHg at randomization may be included if their usual systolic blood pressure measurements are consistently within 85-89 mmHg 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. Previous exposure to KW-3902 2. Pregnant or breast feeding women. Women of child bearing potential must have a negative serum pregnancy test prior to enrollment. 3. Any administration of IV radiographic contrast within 14 days of randomization or any procedures with IV radiographic contrast planned during this hospitalization 4. Administration of IV vasodilators within 6 hours of randomization (with the exclusion of nitrates, which are allowed) 5. Serum potassium 3 mg/dL, albumin 38°C (oral or equivalent) 20. Sepsis or active infection requiring IV anti-microbial treatment 21. Administration of an investigational drug or device or participation in another trial within 30 days before randomization 22. Current or anticipated therapy with atanazavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole 23. Administration of any vasopressor or inotropic drug within 72 hours of randomization (with the exception of ongoing dopamine or dobutamine at doses =5 mcg/kg/min or milrinone at a dose of =0.25 mcg/kg/min, which are allowed IF at a stable dose for the preceding 24 hours AND provided there has been no decrease in SCr during the prior 24 hours) 24. Inability to follow instructions or comply with study procedures 25. Allergy to soybean oil or eggs 26. History of seizure (except febrile seizure) 27. Stroke within 2 years 28. History of brain tumor of any etiology 29. Brain surgery within 2 years 30. Encephalitis/meningitis within 2 years 31. History of penetrating head trauma 32. Closed head injury with loss of consciousness (LOC) over 30 minutes within 2 years 33. History of or at risk for alcohol withdrawal seizures 34. Advanced Alzheimer’s disease 35. Advanced multiple sc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this study is to evaluate the effect of KW-3902 IV, in addition to standard therapy, on the proportion of worsening heart failure and worsening renal function after initiation of therapy through Day 7 or discharge, whichever occurs first.;Secondary Objective: The secondary objectives of this study are to evaluate the effect of KW-3902 IV, in addition to standard therapy, on the the proportion of deaths or rehospitalisations for heart failure or worsening renal function over 30 days, and to estimate and compare within-trial medical resource utilisation and direct medical costs between subjects treated with KW-3902 IV versus placebo.;Primary end point(s): Proportion of treatment failures within 30 days (includes any one of the following criteria): • Death or readmission for heart failure or worsening renal function through 30 days after randomization, OR • 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”: new diuretic initiation or a =50% dose increase of the IV diuretic daily dose, or initiation or increase in dose of oral metolazone or IV chlorothiazide as accompanying therapy to loop diuretics, or initiation of ultrafiltration or initiation of an IV inotrope or an increase in the dose of dopamine, dobutamine, or milrinone if these were in use at the time of randomization or initiation of mechanical ventilatory (including BiPAP or CPAP) or circulatory support OR • Worsening renal impairment as defined by an increase in SCr of =0.3 mg/dL, or the initiation of hemofiltration or dialysis, from the time of randomization to Day 7 or discharge, whichever occurs first. | — |
Countries
Belgium, Germany, Greece, Italy, Netherlands, Poland, United Kingdom
Outcome results
None listed