BACKGROUND
Levosimendan is a calcium-sensitizing drug with inotropic and other properties
that may improve outcomes in patients with sepsis.
METHODS
We conducted a double-blind, randomized clinical trial to investigate whether levosimendan
reduces the severity of organ dysfunction in adults with sepsis. Patients
were randomly assigned to receive a blinded infusion of levosimendan (at a dose of
0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo
in addition to standard care. The primary outcome was the mean daily Sequential
Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores
for each of five systems range from 0 to 4, with higher scores indicating more severe
dysfunction; maximum score, 20). Secondary outcomes included 28-day mortality,
time to weaning from mechanical ventilation, and adverse events.
RESULTS
The trial recruited 516 patients; 259 were assigned to receive levosimendan and
257 to receive placebo. There was no significant difference in the mean (±SD) SOFA
score between the levosimendan group and the placebo group (6.68±3.96 vs.
6.06±3.89; mean difference, 0.61; 95% confidence interval [CI], −0.07 to 1.29;
P=0.053). Mortality at 28 days was 34.5% in the levosimendan group and 30.9%
in the placebo group (absolute difference, 3.6 percentage points; 95% CI, −4.5 to
11.7; P=0.43). Among patients requiring ventilation at baseline, those in the levosimendan
group were less likely than those in the placebo group to be successfully
weaned from mechanical ventilation over the period of 28 days (hazard ratio,
0.77; 95% CI, 0.60 to 0.97; P=0.03). More patients in the levosimendan group than
in the placebo group had supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute
difference, 2.7 percentage points; 95% CI, 0.1 to 5.3; P=0.04).
CONCLUSIONS
The addition of levosimendan to standard treatment in adults with sepsis was not
associated with less severe organ dysfunction or lower mortality. Levosimendan was
associated with a lower likelihood of successful weaning from mechanical ventilation
and a higher risk of supraventricular tachyarrhythmia. (Funded by the NIHR
Efficacy and Mechanism Evaluation Programme and others; LeoPARDS Current
Controlled Trials number, ISRCTN12776039.)