Repetitive use of LEvosimendan in Ambulatory Heart Failure patients (LEIA-HF) - The rationale and study design.

Abstract Purpose Clinical practice forces the necessity to conduct a clinical trial concerning the group of outpatients with chronically advanced heart failure in III or IV NYHA functional class, frequently requiring hospitalizations due to HF exacerbation, and often left without any additional therapeutic option. The current trial aims to determine the efficacy and safety of repeated levosimendan infusions in the group of severe outpatients with reduced ejection fraction (HFrEF). Material and methods LEIA-HF (LEvosimendan In Ambulatory Heart Failure Patients) is a multicentre, randomized, double-blind, placebo-controlled, phase 4 clinical trial to determine whether the repetitive use of levosimendan reduces the incidence of adverse cardiovascular events in ambulatory patients with chronic, advanced HFrEF. A total of 350 patients will be randomized in a 1:1 ratio to receive either levosimendan or placebo, which will be administered as continuous 24 ​h infusions, every 4 weeks for 48 weeks (12 infusions in total – phase I), and followed by double-blind 6 visits, every 4 weeks (phase II of the trial including the option of restarting levosimendan or placebo, based on the fulfillment of additional criteria). The primary endpoint for efficacy assessment will be death from any cause or unplanned hospitalization for HF assessed together, whichever occurs first, in a 12-month follow-up period. Conclusions A well-designed study with a consistent protocol, including the drug side effects, comprehensive clinical assessment, appropriate definition of endpoints, and monitoring therapy, may provide a complete overview of the effectiveness and safety profile of the repetitive levosimendan administration in ambulatory severe HFrEF patients.