A multicentre, randomized, double-blind, placebo controlled study of the effects of KW-3902 Injectable Emulsion on heart failure signs and symptoms, diuresis, renal function, and clinical outcomes in subjects hospitalized with worsening renal function and heart failure requiring intravenous therapy. - REACH UP

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-006843-29-GR
• Date of registration: 17/09/2007
• Prospective Registration: Yes
• Primary sponsor: NovaCardia Inc
• Public title: A multicentre, randomized, double-blind, placebo controlled study of the effects of KW-3902 Injectable Emulsion on heart failure signs and symptoms, diuresis, renal function, and clinical outcomes in subjects hospitalized with worsening renal function and heart failure requiring intravenous therapy. - REACH UP
• Scientific title: A multicentre, randomized, double-blind, placebo controlled study of the effects of KW-3902 Injectable Emulsion on heart failure signs and symptoms, diuresis, renal function, and clinical outcomes in subjects hospitalized with worsening renal function and heart failure requiring intravenous therapy. - REACH UP
• Date of first enrolment: 07/02/2008
• Target sample size: 480
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-006843-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany, Greece, Italy, Netherlands, Poland, United Kingdom

Key inclusion & exclusion 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:
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 CO2 retention or 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, Hct <25%, 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 sc

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Intervention(s)

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
Other descriptive name: Not available
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Emulsion for injection
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

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.

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.

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.

Secondary ID(s)

CKI-303

2006-006843-29-NL