Protocol CKI-302 KW-3902IV in the treatment of subjects with acute heart failure syndrome A multicenter, randomized, double-blind, placebo-controlled study of the effects of KW-3902 injectable emulsion on heart failure signs and symptoms and renal function in subjects with acute heart failure syndrome and renal impairment who are hospitalized for volume overload and require intravenous diuretic therapy

Phase 3

Completed

Conditions: acute cardiac failure / acute decompensated heart failure
10082206
10038430

Registration Number: NL-OMON31606

Lead Sponsor: ovaCardia, Inc. (a wholly owned subsidiary of Merck & Co., Inc.)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 60

Inclusion Criteria

See also pages 46 and 47 of protocol
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 randomization within 24-hours of presentation to the hospital (including time spent in the emergency department). Study drug infusion should start as soom as possiblefollowing randomization, preferably in the morning hours.
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)

Exclusion Criteria

See also pages 47-49 of protocol
9. Pregnant or breast feeding women. Women of child bearing potential must have a negative urine or serum pregnancy test prior to enrollment.
10. Acute contrast induced nephropathy
11. Temperature >38°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment
12. Serum potassium <3.5 mEq/L (3.0-3.4 mEq/L will be allowed if parenteral supplemental potassium is being administered)
13. Ongoing or planned IV therapy for AHFS with positive inotropic agents, vasopressors, vasodilators, or mechanical support (intra-aortic balloon pump, endotracheal intubation, ventricular assist device) with the exception of IV nitrates
14. BNP <500 pg/mL or NT-pro-BNP <2000 pg/mL
15. Ongoing or planned treatment with ultrafiltration, hemofiltration, or dialysis
16. Severe pulmonary disease (as evidenced by pre-admission or current oral steroid
dependency, current treatment with IV steroids, or previous history of CO2 retention or intubation for acute exacerbation)
17. Significant stenotic valvular disease (severe aortic stenosis, mitral stenosis)
18. Heart transplant recipient or admitted for cardiac transplantation
19. Clinical evidence of acute coronary syndrome in the 2 weeks prior to screening
20. AHFS due to significant arrhythmias (ventricular tachycardia, bradyarrhythmias
with slow ventricular rate [<45 beats per minute] or atrial fibrillation/flutter with a rapid ventricular response of >120 beats per minute)
21. Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy. This criterion does not include restrictive patterns seen on Doppler.
22. Known hepatic impairment (total bilirubin >3 mg/dL, albumin <2.8 mg/dL, or increased ammonia levels if performed)
23. Non-cardiac pulmonary edema, including suspected sepsis
24. Administration of an investigational drug or device, or participation in another trial, within 30 days before randomization
25. Current or anticipated therapy with atanazavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole
26. Systolic blood pressure >160 mmHg at randomization
27. Inability to follow instructions or comply with follow-up procedures
28. Allergy to soybean oil or eggs or benzodiazepines
29. History of seizure (except febrile seizure)
30. Stroke within 2 years
31. History of or current brain tumor of any etiology
32. Brain surgery within 2 years
33. Encephalitis/meningitis within 2 years
34. History of penetrating head trauma
35. Closed head injury with loss of consciousness (LOC) over 30 minutes within 2 years
36. History of drug or alcohol abuse or at risk for alcohol withdrawal seizures
37. Advanced Alzheimer*s disease
38. Advanced multiple sclerosis
39. Hgb <8 g/dL, or Hct <25%, or the need for a blood transfusion
40. Previous exposure to KW-3902

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>A categorical outcome of:<br /><br>- treatment success,<br /><br>- patient unchanged, or<br /><br>- treatment failure<br /><br>(definitions see protocol pages 30 and 31).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Time to death or rehospitalization for cardiovascular or renal causes through<br /><br>Day 60.<br /><br>- Proportions of subjects with persistent renal impairment as defined by a SCr<br /><br>increase of >=0.3 mg/dL from randomization to Day 7, confirmed at Day 14, or the<br /><br>initation of hemofiltration or dialysis through Day 7.<br /><br>(page 31 of protocol)</p><br>