The objectives of this study are to evaluate the effect of KW-3902IV, 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…
ID
Source
Brief title
Condition
- Cardiac disorders, signs and symptoms NEC
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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.
Secondary outcome
• Number of days, during the 30 days after randomization, that the subject is
alive and out of the hospital
• Change in dyspnea and general well being as determined by Likert scale at 24
and 72 hours post-randomization
Background summary
This study is conducted to examine if administration of KW-3902IV with
intravenous furesomide in patients with heart failure and renal impairment
results in an improvement of the signs and symptoms of heart failure and renal
impairment.
In patients with acute heart failure diuresis is the therapeutic aim. Diuretics
however frequently cause a vicious circle of deteriorating kidney function and
diminishing diuretic impact. Diuretics ensure that the kidneys extract more
fluid, but as a result the sodium concentrations in the kidneys raise, which
result in a reduced fluid excretion (this happens automatically). KW-3902 now
ensures that certain sensors which are responsible for this mechanism are being
blocked. As a result the diuretic effect of the diuretics remains and improves,
and the kidney function is preserved.
Study objective
The objectives of this study are to evaluate the effect of KW-3902IV, 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, and on the proportion of deaths or
rehospitalizations for heart failure or worsening renal function over 30 days,
and to estimate and compare within-trial medical resource utilization and
direct medical costs between subjects treated with KW-3902IV versus placebo.
Study design
Multicenter, randomized, double-blind, parallel-group, placebocontrolled.
Intervention
Subjects will be randomized in a 1:1 ratio to one of two study arms. The
specific dosing regimen and administration procedures are as follows:
• KW-3902IV 30 mg once daily (total volume 60 mL)
• Placebo once daily (total volume 60 mL)
Study drug (KW-3902IV or placebo) will be administered as a 4 hour infusion.
Study drug will be administered once daily for 3 days or until discharge,
whichever occurs earlier, but study drug will not be administered for less than
2 days
Study burden and risks
Patients have already been hospitalized for heart failure and get the standard
of care. If they particpate in the trial the standard treatment in combination
with the study treatment is continued.
- Blood samples are being taken as standard of care, each morning the study
requires a blood sample is to be taken for analysis in a central laboratory (on
days 1-7 and day 14). The screening values are obtained by means of the
standard blood draw at admission.
- Patients are asked to complete a questionnaire on day 14, 30 (telephone
contact) and 60 (telephone contact) (lasts maximum 10 minutes)
- Patients are are asked on day 180 (telephone contact) to ascertain their
vital status
- Patients are examined on a daily base (days 1-7 and day 14) (standard
physical research) and 2 questions about their dyspnea and general well-being
are asked to assess the primary endpoint.
12651 High Bluff Drive, Suite 200
San Diego, CA 92130
US
12651 High Bluff Drive, Suite 200
San Diego, CA 92130
US
Listed location countries
Age
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. Dyspnea at rest or with minimal exertion at randomization
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.
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 <3.5 meq/L (3.0-3.4 meq/L will be allowed if adequate parenteral supplemental potassium is being administered)
6. Ongoing or planned therapy for heart failure with mechanical circulatory support (intra-aortic balloon pump, endotracheal intubation, ventricular assist device) or ventilatory support (including BiPAP or CPAP)
7. Ongoing or planned treatment with ultrafiltration, hemofiltration, or dialysis during this hospitalization
8. Rapidly progressive acute renal failure as manifested by an increase in SCr >=0.7 mg/dL in a 24-hour period
9. Evidence of acute tubular necrosis (urinary sediment, urinary sodium excretion, biopsy, etc.) or post-obstructive nephropathy or other exogenous causes of acute kidney injury, unrelated to heart failure or its treatment (contrast media, cyclosporine, other nephrotoxins)
10. Severe pulmonary disease (as evidenced by pre-admission or current oral steroid dependency, current treatment with IV steroids, or previous history of intubation for acute exacerbation)
11. Significant stenotic mitral or aortic valvular disease
12. Heart transplant recipient or admitted for cardiac transplantation or LVAD surgery
13. Any major surgery within 2 weeks prior to screening (cardiac or non-cardiac)
14. Clinical evidence of acute coronary syndrome in the 2 weeks prior to screening
15. Hgb <8 g/dL, or active bleeding requiring transfusion
16. Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy. This criterion does not include restrictive patterns seen on Doppler.
17. Known hepatic impairment (total bilirubin >3 mg/dL, albumin <2.8 mg/dL, or increased ammonia levels if performed)
18. Non-cardiac pulmonary edema
19. Temperature >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 sclerosis
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-006843-29-NL |
| CCMO | NL16610.042.07 |