Annals of Intensive Care volume 11 , Article number: 53 Cite this article. Metrics details. The phase 3 multinational SCARLET study evaluated the efficacy and safety of a recombinant human soluble thrombomodulin ART for treatment of sepsis-associated coagulopathy SAC , which correlates with increased mortality risk in patients with sepsis. Although no significant reduction in mortality was observed with ART compared with placebo in the full analysis set FAS , an efficacy signal of ART was observed in subgroups of patients who sustained coagulopathy until the first treatment and those not administered concomitant heparin.
The primary efficacy outcome was day all-cause mortality. Safety outcomes included adverse, serious adverse, and major bleeding events. This analysis assessed patient characteristics and efficacy and safety outcomes in France compared with the rest of the world ROW; excluding France. Baseline characteristics were similar between France and the ROW, but some measurements of disease severity were higher in patients in France.
The greater ARR in France may be related to a higher rate of sustained coagulopathy and lower rate of heparin use. In France and the ROW, The ARRs for these subgroups of patients in France were Results from this exploratory analysis suggest that patients with sustained SAC not receiving concomitant heparin may benefit from ART, a fact that should be confirmed in future studies with more restrictive inclusion criteria.
Sepsis is a life-threatening syndrome associated with multiorgan dysfunction that occurs when a host response to infection is dysregulated [ 1 ]. Sepsis-associated coagulopathy SAC , characterized by an elevated international normalized ratio INR and reduced platelet count PLT , correlates with an increased risk of mortality in patients with sepsis [ 2 ].
In addition, ART exerts anti-inflammatory and antifibrinolytic effects through thrombin-activatable fibrinolysis inhibitor in the presence of thrombin [ 5 ]. Findings in a post hoc analysis of a phase 2b randomized clinical trial of participants with sepsis and suspected disseminated intravascular coagulation suggested that ART 0. In the full analysis set FAS , no statistically significant reduction in day all-cause mortality—the primary efficacy endpoint of the study—was observed in patients who received ART compared with patients assigned to placebo.
