E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Kidney Injury (AKI) in adult ICU patients |
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E.1.1.1 | Medical condition in easily understood language |
Acute Kidney Injury (acute renal failure) in patients admitted to the Intensive Care Unit (ICU) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
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 |
The aim of this study is to evaluate the effect of levosimendan, a novel calcium sensitizer with inotropic, anti-inflammatory, anti-apoptotic and anti-oxidative effects, on renal function in an heterogenous ICU-population with Acute Kidney Injury (stage > Injury according to the RIFLE criteria). |
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E.2.2 | Secondary objectives of the trial |
Study the effects of levosimendan on renal (filtration) function, mortality and urine output. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The patient
* Is admitted to the ICU
* Is > 18 years of age
* Has received the diagnosis of Acute Kidney Injury with a RIFLE score > I (Injury)
* Cardiac output > 3.5L/min |
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E.4 | Principal exclusion criteria |
The patient
* Is entering the ICU for post-operative observation with an estimated length of stays < 24 hours
* Is moribund
* Is pregnant
* Has a mono-kidney due to any cause of a post-renal obstruction
* Has been receiving renal replacement therapy due to chronic kidney disease before admission to the ICU
* Is known with hypersensitivity from previous treatments
* Has severe hypotension (MAP < 60mmHg) and/or tachycardia (>180/min) despite measures
* Is known with significant pre-existing mechanical obstruction affecting ventricular filling or outflow.
* Has severe hepatic impairment (ALAT or ASAT >400U/L)\
* Is known with torsade des pointes
Furthermore, the patient will be excluded if treating physician has judged participation in this study as undesirable. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The aim of the present study is to evaluate whether the clinical use of levosimendan in a heterogeneous study population of ICU patients with early AKI according to AKI-biomarker Neutrophil Gelatinase-Associated Lipocaline (NGAL) is able to improve kidney function expressed by an improved endogenous creatinine clearance of 10 mL/min within 72 hours. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Renal function will be assessed at the start of levosimendan-administration and after 24, 48 and 72 hours. |
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E.5.2 | Secondary end point(s) |
The secondary objectives are:
* To evaluate the effect of levosimendan on renal oxygen extraction, defined as the difference between renal venous oxygen saturation and arterial oxygen saturation.
* To evaluate the effect of levosimendan on the urinary NGAL-levels, eGFR and urinary output
* To evalute the effect of levosimendan on cardiac output and contractility
* To assess the need for renal replacement therapy (RRT)
* To assess mortality in both groups at 28- and 45 days. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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Active participation in this study will end 72 hours after initiation of levosimendan administration. Mortality will be assessed by 28 and 45 days. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |