E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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 |
The primary efficacy objective of the study is to compare the effects of a pulsed application of Levosimendan versus placebo of the composite end-point functional capacity and quality of life. |
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E.2.2 | Secondary objectives of the trial |
The secondary efficacy objectives are to determine the effects of a pulsed administration of levosimendan on: a) short-term (8 weeks from randomization) and long-term (24 weeks from randomization) event-free survival (cardiac death or heart failure-related hospitalization), b). Components of primary endpoints (6-minute walk test and KCCQ) will be analysed as separate endpoints.
Cardiac death will be divided into arrhythmic death and pump failure death. Adjudication of endpoints is assigned to the independent Data Safety and Monitoring Board.
The tertiary efficacy objective is to determine theeffect of a pulsed application of levosimendan on: a) marker of inflammatory activation (IL-6, IL-10 and TNF-alpha) b) markers of the apaptotic process (Afas, SFAS, Ligand), c) markers of oxidative stress (MDA, protein carbonyls, nitrotyrosine) d) markers of disease severity (NT-pro-BNP) e) weight f) dose of diuretics g) creatinine clearance and h) cost effectiveness |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
MRI Sub-study:
Aim of the substudy:
- Proof evidence for reverse remodeling and improvement of left ventricular function by Levosimendan, - Assessment of hibernating myocardium activated by Levosimendan.
Economic Valuation Sub Study:
Aim of the study:
- To determine the cost-effectiveness of pulsed infusion of Levosimendan in outpatients with advanced heart failure.
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E.3 | Principal inclusion criteria |
- Patients with chronic stable heart failure NYHA III and IV diagnosed at least 3 months before inclusion - 6-min.-walk-test < 350 meters - EF < 35 % - age > 20 years - optimized and individualised neurohormonal background therapy according to ESC-guidelines for the treatment of chronic heart failure. - Patient has signed informed consent
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E.4 | Principal exclusion criteria |
→ Hospitalization for decompensated heart failure requiring i.v. diuretics within the last month before randomization → History of torsades des pointes → Allergy to Levosimendan or any of the excipients → Administration of inotropes in the last 4 weeks → Potassium < 3,5 and >5,5 mmol/l → Systolic blood pressure <= 100 mmHg → For Austria and Greece: Women at childbearing age without using effective contraceptives ( oral contraceptives, intrauterine contraceptive devices) unless surgical sterilisation has been undertaken. → For Germany: Women of childbearing age unless surgical sterilisation has been undertaken → Female patients who are pregnant or nursing → Creatinin Clearance < 30ml/min/m2 → Severe anemia (Hb < 10 mg /dl) → Mechanical obstruction affecting the ventricular filling or the outflow or both → Patients with non compliance → Severe conditions, which make the patient unsuitable to participate in a study as judged by the investigator → Severe liver disease → Percutaneous coronary intervention within the last 1 months → Coronary bypass surgery within the last 3 months → Planned HTX within the next six months → Patient involved in another clinical trial → De-nove heart failure → Implantation of a cardiac resynchronisation device during the last three months
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E.5 End points |
E.5.1 | Primary end point(s) |
Proporation of patients showing an improvement in the six-minutes walk-testof 20 % or more and 15 % or higher scoring in the Kansas City Cardiomyopathy Questionnaire (KCCQ) at the end of the 28 week study period. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | 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 | 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.8.3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | Information not present in EudraCT |
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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End of the Trial = Last Patient - Last Visit |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |