Aims
The Leodor Trial objectives are to show that repetitive levosimendan infusions are effective and safe in stabilizing patients with advanced chronic heart failure during a vulnerable period following a recent hospitalization.
A randomized, double-blind, placebo-controlled multicenter study with parallel group design.
Heart failure (HF) is the leading cause of adult hospitalization in the industrialized world and imposes a substantial burden on the public health. The later stages of heart failure are characterized by a steady decline in quality of life and frequent re-hospitalization for recurrent acutization of the symptoms (Fruhwald 2016).
Patient count so far: Email the team
Most of the re-hospitalisations take place relatively soon after discharge from the index hospitalisation. About one quarter of patients are re-hospitalized within one month, and more than 60% of these re-hospitalisations are seen within 15 days after discharge (Dharmarajan 2013).
Therapeutic options are limited and drugs used for chronic heart failure often have to be withdrawn owing to side effects such as hypotension or worsening of renal function. As prognosis deteriorates and treatment options become restricted clinical priorities should be recast to emphasize maintaining functional capacity and quality of life (Fruhwald 2016).
Several clinical studies have been performed on the repetitive use of intravenous levosimendan. Their results are suggesting that repeated infusions of levosimendan bring advantages to patients with advanced chronic heart failure. However, some of these studies were open-label, single-center studies and even the largest double-blind studies included a limited number of patients. Therefore, a larger study would be needed to verify the favorable results.
In the LEODOR study the efficacy and safety of intermittent levosimendan therapy started during the vulnerable phase after a recent hospitalisation for heart failure is tested. The over-arching hypothesis of the study is that, compared with placebo, repetitive administration of levosimendan in the post-acute heart failure syndrome discharge period, will be associated with greater clinical stability through 14 weeks as assessed by a composite clinical endpoint consisting of mortality, acute heart failure episodes and change in natriuretic peptide levels.
References: Fruhwald S et al. Expert Rev Cardiovasc Ther. 2016;14:1335-1347. Dharmarajan K et al. BMJ. 2013 Nov 20;347:f6571
To date, 10 clinical studies (of which 7 double blind clinical trials) have been performed on the repetitive use of levosimendan. Their results are univocally consistent with the hypothesis that repeated infusion of levosimendan brings advantages to patients in Advanced Heart Failure. However, only a limited amount of patients were enrolled and a bigger study, properly powered, is warranted.
The Leodor Trial objectives are to show that repetitive levosimendan infusions are effective and safe in stabilizing patients with advanced chronic heart failure during a vulnerable period following a recent hospitalization.
Leodor Trial is multicentre, randomised, double-blind, placebo-controlled study in patients with severe chronic heart failure. Patients will receive either a 6-hour infusion every 2 weeks or a 24-hour infusion every 3 weeks up to 12 weeks, followed by a follow-up visit 1 at week 14 and a follow-up visit 2 at week 26. The study will use a parallel group design.
It has been shown from a large trauma RCT that early treatment for bleeding has better outcomes. This study will also look at laboratory and clinical outcome measures.
Patients will not be included into this study if they meet any of the following criteria:
Patients must meet all of the following criteria to be included into the study:
The primary efficacy objective of the study is to compare the effects of pulsed application of levosimendan versus placebo in patients with advanced chronic heart failure during a vulnerable period of 14 weeks following a recent hospitalisation on a global rank endpoint in which all participants are ranked across three hierarchical groups:
Project Manager - Medical University Innsbruck, Austria
Project Manager - Medical University Innsbruck, Austria
Leodor Trial Principal Investigator; Chief of the Heart Failure and Heart Transplant Program, Medical University Innsbruck, Austria
Hospital Universitario de Bellvitge. Barcelona, Spain
"Umberto I" Hospital, "La Sapienza" University, Rome, Italy
Hospital Universitario de La Laguna. Tenerife, Spain
Copenhagen University Hospital, Copenhagen, Denmark
Hospital Sanitas Cima, Barcelona, Spain
Hospital 12 de Octubre, Madrid, Spain
University Hospital Würzburg, Würzburg, Germany
Akademiska University Hospital, Uppsala, Sweden
Faculty of Medicine, University of Debrecen, Debrecen, Hungary
University Medical Centre, Ljubljana, Slovenia
Head, Clinical Studies Coordination Center Medical University Innsbruck, Austria