E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced chronic heart failure |
|
E.1.1.1 | Medical condition in easily understood language |
Severe chronic reduced heart function |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
E.1.2 | System Organ Class | 100000004849 |
|
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 subacute effect of levosimendan infusion on exercise capacity and exercise hemodynamics compared with placebo in patients with advanced chronic heart failure. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥18 years • NYHA III-IV on optimal medical treatment • LVEF ≤35% • NT-proBNP >600 µg/L • pVO2 <20 ml/kg/min • No hospitalization for HF or change in loop diuretic <2 weeks
|
|
E.4 | Principal exclusion criteria |
• Recent or acute coronary and respiratory syndromes • Recent sustained ventricular tachycardia or ventricular fibrillation • Severe aortic or mitral valve disease • Known malfunctioning artificial heart valve • Uncorrected obstructive valvular disease • Hypertrophic cardiomyopathy • Fertile women • Uncorrected thyroid disease • Presence of any disease/condition that might per se influence exercise performance • Left ventricular assist device • Pacemaker-guided heart rate at rest or during exercise • Known contraindication for treatment with levosimendan • Any treatment with levosimendan in the previous 6 months • Inability to perform a VO2max test • Symptomatic hypotension or systolic blood pressure < 90 mmHg
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Change in CO/PCWP (ΔCO/PCWPV1-V3submax) at day 5 (visit 3) after 6 hour infusion of levosimendan (visit 1) at the workload corresponding to 50% of pVO2 determined at baseline (visit 0). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Measure change in the above mentioned parameter at day 5 (visit 3) after 6 hour infusion of levosimendan at randomization (visit 1) at the workload corresponding to 50% of pVO2 determined at baseline (visit 0). |
|
E.5.2 | Secondary end point(s) |
• Change in CO/PCWP (ΔCO/PCWPV1-V3max) at peak exercise • Change in maximal CO (ΔCOV1-V3) at peak exercise • Change in PCWP (ΔPCWPV1-V3) at the maximal load obtained during both invasive measurements • Maximal CO, PCWP, SvO2 and workload at visit 3 • Change in resting PCWP, CO, CVP, mPA • Change in 6 MWT at day 3(Δ6MWTV1-V2), 7 (Δ6MWTV1-V3) and 14 (Δ6MWTV1-V4) • Change in NT-proBNP at day 3(ΔNTproBNPV1-V2), 7 (ΔNTproBNPV1-V3) and 14 (ΔNTproBNPV1-V4) • QOL at day 3, 7 and 14. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Measure change in the above mentioned parameters at day 5 (visit 3) after 6 hour infusion of levosimendan at randomization (visit 1) at the workload corresponding to 50% of pVO2 determined at baseline (visit 0). |
|
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 | No |
E.6.5 | Efficacy | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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
| 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 | 2 |
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 | Yes |
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
|
It is the last visit of the last subject enter LVLS |
|
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 |