LeoPARDS
Trial question
What is the role of levosimendan in patients with sepsis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
44.0% female
56.0% male
N = 515
515 patients (226 female, 289 male).
Inclusion criteria: adult patients with sepsis who had received vasopressors for at least 4 hours.
Key exclusion criteria: ESRD; severe chronic hepatic impairment; previous treatment with levosimendan within 30 days; history of torsades de pointes; hypersensitivity to levosimendan.
Interventions
N=258 levosimendan (at a dose of 0.05-0.2 mcg/kg/minute for 24 hours plus standard care).
N=257 placebo (matching placebo for 24 hours plus standard care).
Primary outcome
Mean Sequential Organ Failure Assessment score over stay in the intensive care unit
6.68 points
6.06 points
6.7 points
5.0 points
3.3 points
1.7 points
0.0 points
Levosimendan
Placebo
No significant
difference ↔
No significant difference in mean SOFA score over the stay in the ICU (6.68 points vs. 6.06 points; AD 0.61 points, 95% CI -0.07 to 1.29).
Secondary outcomes
No significant difference in death at 28 days (34.5% vs. 30.9%; AD 3.6%, 95% CI -4.5 to 11.7).
No significant difference in the rate of major acute kidney events within 28 days (57.4% vs. 54.3%; AD 3.1%, 95% CI -5.5 to 11.6).
No significant difference in ventilator-free days (16 days vs. 19 days; AD -3 days, 95% CI -9.5 to 1).
Safety outcomes
No significant differences in serious adverse event, life-threatening arrhythmia, and bradycardia.
Significant difference in supraventricular tachyarrhythmia (3.1% vs. 0.4%).
Conclusion
In adult patients with sepsis who had received vasopressors for at least 4 hours, levosimendan was not superior to placebo with respect to mean SOFA score over the stay in the ICU.
Reference
Anthony C Gordon, Gavin D Perkins, Mervyn Singer et al. Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis. N Engl J Med. 2016 Oct 27;375(17):1638-1648.
Open reference URL