A multicentre, randomised, 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 hospitalised for volume overload and require intravenous diuretic therapy. - PROTECT-2

Phase 1

• Conditions: 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

• Registration Number: EUCTR2006-001637-18-FI
• Lead Sponsor: ovaCardia Inc (wholly owned subsidiary of Merck & Co. Inc)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2006-07-03
• Study Completion: 2009-07-30
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 920

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

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 <3.5 mEq/L (3.0-3.4 mEq/L will be allowed if parenteral supplemental potassium is being administered)
5. Ongoing or planned IV therapy for AHFS with positive inotropic agents, vasopressors, vasodilators, or mechanical support (intraaortic balloon pump, endotracheal intubation, ventricular assist device) with the exception of IV nitrates
6. BNP <500 pg/mL or NT-pro-BNP <2000 pg/mL
7. Ongoing or planned treatment with ultrafiltration, hemofiltration, or dialysis
8. 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)
9. Significant stenotic valvular disease (severe aortic stenosis, mitral stenosis)
10. Heart transplant recipient or admitted for cardiac transplantation
11. Clinical evidence of acute coronary syndrome in the 2 weeks prior to screening
12. 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)
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 <2.8 mg/dL, or increased ammonia levels if performed)
15. Non-cardiac pulmonary edema, including suspected sepsis
16. Administration of an investigational drug or device, or participation in another trial, within 30 days before randomization
17. Current or anticipated therapy with atanazavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole
18. Systolic blood pressure >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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified