In short
Sivelestat is a neutrophil elastase inhibitor, a type of drug that blocks an enzyme involved in inflammation. It is being studied in a Phase 2 clinical trial for septic coagulopathy, a blood-clotting complication of sepsis, with 120 participants planned. The trial is currently authorised but not yet recruiting.
Table of contents
Key points
- Phase 2 randomised controlled trial evaluating sivelestat in septic coagulopathy
- Planned enrollment of 120 participants
- Trial status: Authorised (not yet recruiting)
- Primary outcome: changes in plasma plasminogen levels after 24 hours of treatment
- Sivelestat is also known as Elaspol and is used in Japan for acute lung injury
What is sivelestat?
Sivelestat, also known as sivelestat sodium or by the trade name Elaspol, is a neutrophil elastase inhibitor. It is a chemically synthesised small-molecule drug. In Japan, sivelestat is approved for the treatment of acute lung injury and acute respiratory distress syndrome (ARDS). In the European Union clinical trial registry, it is being investigated as an investigational substance for septic coagulopathy.
How does sivelestat work?
Sivelestat blocks the activity of neutrophil elastase, an enzyme released by neutrophils (a type of white blood cell) during inflammation. Neutrophil elastase can damage lung tissue and contribute to acute lung injury. By inhibiting this enzyme, sivelestat may reduce inflammation and tissue damage. In animal studies, sivelestat reduced lipopolysaccharide-induced lung injury in rats. The molecular target of sivelestat is the enzyme ELANE (neutrophil elastase).
Which conditions is sivelestat used or studied for?
- Septic coagulopathy — a blood-clotting disorder that develops in people with sepsis; the Phase 2 trial is testing whether sivelestat can restore normal clot breakdown in these patients.
- Acute lung injury — damage to the lungs caused by inflammation; Sivelestat is approved in Japan for this condition.
- Acute respiratory distress syndrome (ARDS) — a severe form of lung failure; Sivelestat is used for this in Japan.
- Cardiopulmonary bypass-related acute lung injury — lung damage after heart surgery using a heart-lung machine; a retrospective study suggested sivelestat may reduce pneumonia and shorten mechanical ventilation time in these patients.
- Liver ischemia and reperfusion injury — damage to the liver when blood supply is restored after being blocked; preclinical research has explored a protective role for neutrophil elastase inhibitors.
How is sivelestat given?
Sivelestat is given by intravenous infusion. In the Phase 2 trial, the dose under investigation is 0.2 mg per kilogram of body weight per hour. The pharmaceutical form is a solution for intravenous use. In the cardiopulmonary bypass study, sivelestat was administered at the same dose of 0.2 mg/kg/h for 3 days.
What do the clinical trials show?
One clinical trial of sivelestat is registered in the EU Clinical Trials Information System. It is a Phase 2b multicentre randomised controlled trial evaluating the efficacy of sivelestat compared with placebo in 120 patients with septic coagulopathy. The trial is currently authorised but has not yet started recruiting participants.
The trial focuses on patients with septic shock who also have coagulopathy, defined by a positive CIS score of 4 points or more. The main measure (primary outcome) is the change in plasma plasminogen levels after 24 hours of treatment with either placebo or sivelestat. Plasminogen is a protein involved in breaking down blood clots, so this measure reflects how well the body's clot-dissolving system is working.
Because the trial has not yet reported results, there are no efficacy findings from this study to describe yet. Results from earlier research outside the registry are mixed: a case-control study in patients after emergency cardiovascular surgery found no significant difference in 30-day mortality between sivelestat and control groups, but did find a significant reduction in pneumonia (40% vs 62%) and shorter mechanical ventilation time (median 96 hours) in the sivelestat group.
What side effects are known?
The supplementary sources provided do not contain a detailed side-effect profile for sivelestat. The cardiopulmonary bypass study reported adverse outcomes including 30-day mortality, stroke, need for ECMO (extracorporeal membrane oxygenation), continuous renal replacement therapy, and intra-aortic balloon pump use, but none of these differed significantly between the sivelestat and control groups.