Efficacy and safety of human soluble thrombomodulin (ART-123) for treatment of patients in France with sepsis-associated coagulopathy: post hoc analysis of SCARLET

Annals of Intensive Care

Xavier Wittebole¹  Jean-Louis Vincent²  David Fineberg³  Kosuke Tanaka⁴  Toshihiko Kayanoki⁴  Julie Helms⁵  Bruno François⁶  Emmanuelle Mercier⁷  Maud Fiancette⁸  Jean-Baptiste Lascarrou⁹ 

[1] Department of Critical Care Medicine, Clinique Universitaire St Luc, UCLouvain, Brussels, Belgium;Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium;Department of Medical Affairs, Asahi Kasei Pharma America Corporation, Waltham, MA, USA;Department of Program Management & Scientific Affairs, Asahi Kasei Pharma America Corporation, Waltham, MA, USA;Faculté de Médecine, Hôpitaux universitaires de Strasbourg, Service de Médecine Intensive - Réanimation, Nouvel Hôpital Civil, Université de Strasbourg (UNISTRA), Strasbourg, France;ICU Department, Inserm CIC-1435 & UMR-1092, CRICS-TRIGGERSEP, CHU Dupuytren, 2 Av Martin Luther King, 87042, Limoges, France;Médecine Intensive Réanimation, CRICS-TRIGGERSEP, CHRU de Tours, Tours, France;Service de Médecine Intensive Réanimation, Centre Hospitalier Départemental Vendée, La Roche-sur-Yon, France;Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Nantes, Nantes, France;

关键词: Sepsis;    Sepsis-associated coagulopathy;    Thrombomodulin;    ART-123;    Heparin;    France;   

DOI  :  10.1186/s13613-021-00842-4

来源: Springer

【 摘 要 】

BackgroundThe phase 3 multinational SCARLET study evaluated the efficacy and safety of a recombinant human soluble thrombomodulin (ART-123) 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-123 compared with placebo in the full analysis set (FAS), an efficacy signal of ART-123 was observed in subgroups of patients who sustained coagulopathy until the first treatment and those not administered concomitant heparin. Post hoc analysis was performed of patients treated in France, the country with the largest enrollment (19% of the FAS) and consistent patient enrollment throughout the study duration.MethodsAdult patients with SAC (international normalized ratio > 1.4; platelets > 30 × 109/L to < 150 × 109/L or platelet decrease > 30% within 24 h) and evidence of bacterial infection were included. The primary efficacy outcome was 28-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). Mortality rates were assessed in patients in France or the ROW with characteristics previously associated with ART-123 efficacy.ResultsBaseline characteristics were similar between France and the ROW, but some measurements of disease severity were higher in patients in France. The 28-day all-cause mortality absolute risk reductions (ARRs) with ART-123 were 8.3% in France and 1.1% in the ROW. 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, 84.6% and 78.0% of patients sustained coagulopathy from the time of initial SAC diagnosis to first treatment with the study drug, and 65.8% and 43.9% did not receive heparin, respectively. The ARRs for these subgroups of patients in France were 13.4% and 16.6%, respectively. Safety of ART-123 was comparable between France and the ROW.ConclusionsResults from this exploratory analysis suggest that patients with sustained SAC not receiving concomitant heparin may benefit from ART-123, a fact that should be confirmed in future studies with more restrictive inclusion criteria.

【 授权许可】

CC BY