December 2017 post
12/5/2017 2:54:59 PM
Hospitalisation for the management of acute decompensation is a critical moment in the trajectory of heart failure (HF) and one that has gloomy prognostic implications for many patients. Outcomes for patients hospitalized with acute HF are poor, with high mortality and recurrent hospitalizations. The majority of those re-hospitalisations occur early after first hospital discharge: about a quarter of acute HF patients are re-hospitalised within the first month, and two-thirds within 1 year.
We have disappointingly few good options to offer patients during this period of vulnerability. Intermittent or continuous conventional inotropic therapy has been tested but, despite favourable indications from pilot trials, no positive effect on hospitalisations has been observed and possibly no benefit on mortality either.
Several clinical studies of the repetitive use of i.v. levosimendan have suggested that such a strategy may benefit patients with advanced HF, which was confirmed by the recent meta-analyses by Silvetti et al. A larger study, however, is needed to verify these favourable preliminary results and to explore the efficacy and safety of intermittent levosimendan therapy during the period of high vulnerability that follows a hospitalisation for acute HF.
The LeoDOR study has been designed to address this need. As a multicentre, randomised, double-blind, placebo-controlled, three-arm trial LeoDOR will explore the efficacy and safety of intermittent levosimendan therapy, given for 12 weeks either as a 6-h continuous infusion at a rate of 0.2 μg/kg/min every 2 weeks or as a 24-h continuous infusion at a rate of 0.1 μg/kg/min every 3 weeks.
Efficacy assessment in LeoDOR is based on a novel and ambitious composite outcome. in which all participants are ranked across three hierarchical groups in order of importance: top of that ranking comes (i) time to death or urgent heart transplantation or implantation of a ventricular assist device (VAD), followed by (ii) time to non-fatal HF requiring i.v. vasoactive therapy; and (iii) time-averaged proportional change in N-terminal pro-brain natriuretic peptide (NT-proBNP). This imaginative outcome measure assigns proper weight to different outcomes and also enables every patient to contribute to the endpoint.
The first patients will be enrolled in LeoDOR this month, December 2017 and will continue until Q2 2019, when it is planned to have enrolled 264 patients at 28 centres in nine European countries. The LeoDOR study may bring some much-needed good news for a growing population of acutely ill HF patients and those responsible for their care.