E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acutely decompensated heart failure |
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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 primary objective of the study is to compare the efficacy of levosimendan to dobutamine on "All-cause mortality" in the 180 days following randomisation. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of levosimendan compared to dobutamine on: "Number of days alive out of hospital" during the 180 days following randomisation. "All-cause mortality" during the 31 days following randomisation. "Cardiovascular mortality" during the 180 days following randomisation. "Global Assessment" at 24 hours following randomisation. Change in patient's evaluation of dyspnoea at 24 hours following randomisation. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Written, signed, and dated informed consent. 2. Male and female patients over 18 years of age. Females of child bearing potential must have a negative pregnancy test and must refrain from breastfeeding. Women who are postmenopausal [(two years since last menstrual cycle] , surgically sterilised or have undergone a hysterectomy are considerd not to be of child bearing potential. 3. Hospitalised patients with acutely decompensated heart falure. 4. Left ventricular ejection fraction less than or equal to 30% as assessed using echocardiography, radionuclide ventriculography or contrast angiography within 12 months. 5. Clinical need for intravenous inotropic support as evidenced by insufficient response to intravenous diuretics and/or vasodilators (nitroglycerin, nitroprusside) and at least one of the following at screening: oligouria (mean urine output <30 ml/h for at least 6 hours) and not a results of hypovolemia. dyspnoea at rest or mechanical ventilation for heart failure haemodynamic impairment in those patients with Swan-Ganz catheter inserted (PCWP > or= 18 mm Hg and/or Cardiac Index < or = 2.2 l/min/m2.
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E.4 | Principal exclusion criteria |
1. Severe obstruction of ventricular outflow tracts such as haemodynamically significant uncorrected primary valve disease or hypertrophic cardiomyopathy or impaired ventricular filling such as restrictive cardiomyopathy. 2. Weight > or = 160kg. 3. Cardiac surgery within 30 days before screening. 4. Stroke within 3 months before screening. 5. Systolic blood pressure persistently less than 85 mmHg at screening or baseline. 6. Heart rate persistently 130 bpm or greater at screening or baseline. 7. Serum potassium less than 3.5 mmol/l at screeing. 8. Administration of any inotropic agent (e.g. dobutamine, milrinone, amrinone enoximone, epinephrine, norepinephrine) except digitalis or dopamine (with doses less than or equal than 2 microg/kg/min) during the current hospitalisation. 9. Hypersensitivity to levosimendan or dobutamine or any of their excipients. 10.A history of Torsades de Pointes. 11. Severe renal insufficiency (serum creatine > 450 micromol/l [5.0 mg/dl]) or on dialysis. 12. Significant hepatic impairment at discretion of the investigator. 13. Acute bleeding. 14. Severe anemia (haemoglobin < 8 g/dl) at screening. 15. Septicaemia or septic shock. 16. Other serious diseases limiting life expectancy considerably (e.g. end stage cancer). 17. Participation in a clinical trial with any experimental treatment within 30 days prior to sreening or previous participation in the present study. 18. Administration of levosimendan within 30 days prior to screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective is to compare the efficacy of levosimendan and dobutamine on "All-cause mortality" in the 180 days following randomisation.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 |
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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
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Last visit of last patient |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |