E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heart failure associated with worsening renal function requiring intravenous (IV) therapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10007539 |
E.1.2 | Term | Cardiac disorder signs and symptoms |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Able to provide written informed consent, or a legally authorized representative is able to provide written informed consent
Male or female 18 years of age or greater
Dyspnea at rest or with minimal exertion at randomization
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
Estimated creatinine clearance (CrCl) between 2060 mL/min usingthe Cockcroft-Gault equation (corrected for height in edematoussubjects ≥100 kg) based on a serum creatinine (SCr) value drawnwithin approximately 6 hours of randomization
Worsening renal function as manifested by one of the followingpresent at randomization:An increase in SCr of at least 25% or 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% or 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)
Anticipated need for IV diuretic treatment for at least 48 hours after the start of study drug
BNP >500 pg/mL or NT-pro-BNP >2000 pg/mL
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. |
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E.4 | Principal exclusion criteria |
Previous exposure to KW-3902
Pregnant or breast feeding women.
3.Any administration of IV radiographic contrast within 14 days of
randomization or any procedures with IV radiographic contrast
Severe pulmonary disease
Significant stenotic mitral or aortic valvular disease
Heart transplant recipient or admitted for cardiac transplantation or
LVAD surgery
Any major surgery within 2 weeks prior to screening (cardiac or
non-cardiac)
Allergy to soybean oil or eggs
History of seizure (except febrile seizure)
Stroke within 2 years
History of brain tumor of any etiology
Brain surgery within 2 years
Encephalitis/meningitis within 2 years
History of penetrating head trauma
Closed head injury with loss of consciousness (LOC) over 30 minutes within 2 years
History of or at risk for alcohol withdrawal seizures
34. Advanced Alzheimers disease
35. Advanced multiple sclerosis |
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E.5 End points |
E.5.1 | 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 renalfunction through 30 days after randomization,OR Worsening symptoms and signs of heart failure occurring >24hours after the start of study drug to Day 7 or discharge,whichever occurs first, such that there is a need for any one ofthe following types of rescue therapy:o 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,oro initiation of ultrafiltrationoro 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 randomizationoro initiation of mechanical ventilatory (including BiPAP or CPAP) or circulatory supportOR Worsening renal impairment as defined by an increase in SCr of≥0.3 mg/dL, or the initiation of hemofiltration or dialysis, fromthe time of randomization to Day 7 or discharge, whicheveroccurs first. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |