March 2019 post

3/5/2019 1:41:47 PM

It’s a year since I reported on the status of the LeoDOR study (Repetitive Levosimendan Infusion for Patients With Advanced Chronic Heart Failure) so I think it’s more than time to bring readers up to date with our progress.

Since I last wrote on this subject the protocol for the study, authored by myself and 13 distinguished colleagues, has been published [Pölzl G et al. ESC Heart Failure 2019;6(1):174-181 DOI:10.1002/ehf2.12366].

The trial’s dedicated website, https://leodortrial.com/, is up and running and offers information to prospective patients and investigators, including a Trial Information Sheet and Site Evaluation documents for the latter and clear plain language answers to questions such as “What is the purpose of this study” and “What does taking part in this study involve?” for the former. LEODOR researchers can keep up-to-date and exchange thoughts and information via the sharepoint facility operated via the website.

The first 10% of the planned 264 patients have been enrolled, and the dedicated Twitter feed (@LeodorTrial) has announced the participation of several centres in Germany, including Innsbruck (where the first patient was recruited), Linz, Berlin, Braunau, Kiel, Würzburg, plus Oulu (Finland), Debrecen (Hungary) and Ljubljana (Slovenia).

Underpinning and inspiring all these exertions is the fact that while findings from over 10 double-blind clinical trials or registries (including LevoRep, LION-HEART, LAICA, RELEVANT, etc.) have consistently supported the view that repeated infusion of levosimendan benefit patients with advanced heart failure, no single study has been statistically powered enough to generate conclusive results. Clearly, a larger study is needed and it is our confident hope that LeoDOR (NCT03437226) will be that trial.

LeoDOR is the first major trial of intermittent levosimendan to use a global rank score methodology to assess the impact of therapy. This global rank endpoint is a composite of: (i) time to death or urgent heart transplantation or VAD implantation: (ii) time to a non-fatal HF event requiring i.v. vasoactive therapy, and: (iii) time-averaged proportional change in NT-proBNP from baseline to 14 weeks. This novel methodology allows each patient to contribute to the overall endpoint, thereby optimizing statistical power while keeping the number of patients within manageable limits.

We’re a way off seeing the final results of LeoDOR yet and I expect to deliver more updates via this blog before that day arrives, but the study is now well and truly underway: I extend my best wishes and gratitude to all patients and investigators who have agreed to contribute to this important initiative in advanced heart failure treatment.