Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis

Enrol a patient to the study

For investigators

Sepsis is the leading cause for admission to an intensive care unit in the UK. More than a decade ago it was estimated that the costs to the NHS of treating sepsis were in the order of £700 million. However, with the aging of our population and increasing complexity of health care this figure is likely to be much higher now and may continue to rise.

Aims

The LeoPARDS trial is designed primarily to identify whether levosimendan reduces the incidence and severity of acute organ dysfunction in adult patients who have sepsis. In addition, we are investigating the effect of levosimendan on the function of individual organs and its safety profile in sepsis. The latter question is in part being answered by studying the pharmacokinetics of levosimendan in patients with sepsis. We are also investigating the mechanisms by which levosimendan might exert its effects.

The trial

LeoPARDS is a randomized, double-blind, placebo-controlled multi-centre trial. Adult patients with suspected or confirmed infection and 2 or more SIRS criteria who are dependent on vasopressors to maintain their blood pressure are eligible for enrolment. Once eligibility criteria are met there is a 24 hour window for recruitment to the trial. Enrolled patients will be randomized to receive either levosimendan 0.05 to 0.20 μg/kg/min or placebo for 24 hours. We are looking to recruit a total of 516 patients over 2 1/2 years.

Exclusion criteria

  • More than 24 hours since meeting all the inclusion criteria
  • End-stage renal failure at presentation (previously dialysis-dependent)
  • Severe hepatic impairment (Child-Pugh class C)
  • A history of Torsades de Pointes
  • Known significant mechanical obstructions affecting ventricular filling or outflow or both.
  • Treatment limitation decision in place (eg DNAR or not for ventilation/ dialysis)
  • Known or estimated weight >135kg
  • Known to be pregnant
  • Previous treatment with levosimendan within 30 days
  • Known hypersensitivity to levosimendan or any of the excipients
  • Known to have received another investigational medicinal product within 30 days or currently in another interventional trial that might interact with the study drug.

Outcome measures

The primary outcome measure will be the mean SOFA score between treatment groups. We are also looking at number of secondary outcomes – these include oxygen delivery (ScvO2) & cardiac output; incidence & duration of renal failure (AKIN criteria); serum bilirubin; time to extubation; 28-day, hospital and three & six-month survival; ICU and hospital length of stay, and ICU-free days; duration of renal replacement therapy; days free from catecholamine therapy.