Summary for Medical Professionals & Investigators

Thrombomodulin alfa (ART-123) is a recombinant protein consisting of the extracellular domains of thrombomodulin, which is a thrombin binding protein expressed on the surface of endothelial cells. When thrombin is bound to thrombomodulin the resulting complex blocks the fibrinogen binding sites on thrombin, and converts the zymogen protein C to activated protein C (APC). APC inactivates procoagulant cofactors Va and VIIIa inhibiting thrombin formation. Additionally, thrombomodulin has been shown to have anti-inflammatory effects by blocking thrombin-induced activation of platelets and endothelial cells, and blocking the inflammatory mediator HMGB1 from signaling endothelial cell receptors.

Bacterial sepsis is the most common cause of disseminated intravascular coagulation (DIC) with coagulopathy occurring in 20-35% of patients, and DIC may double the mortality of sepsis. DIC is triggered by thrombin activation via the tissue factor pathway. This causes an increase in endothelial permeability, increased conversion of fibrinogen to fibrin, and a result of small to midsize vessel occlusion that causes organ dysfunction, Depletion of platelets and coagulation factors may also cause bleeding.

ART-123 under the trade name Recomodulin was approved in Japan in 2008 for treatment of DIC. ART-123 is currently being studied in a global phase 3 randomized placebo controlled safety and efficacy study entitled the SCARLET study. Patients enrolled in this study must be receiving treatment in an intensive care setting for sepsis with a confirmed bacterial source and have associated cardiac or pulmonary dysfunction and coagulopathy caused by the sepsis. We are currently seeking new investigators and are eager to discuss this study with potential new sites. The link to the clinicaltrials.gov website is shown below.

View our clinical Trial on clinical trials gov site.

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Vincent. A Randomized, Double-Blind, Placebo-Controlled, Phase-2B Study to Evaluate the Safety and Efficacy of Recombinant Human Soluble Thrombomodulin, ART-123, in Patients with Sepsis and Suspected Disseminated Intravascular Coagulation. Crit Care Med. 2013 Sep;41(9):2069-79