Recombinant Human-Soluble Thrombomodulin Contributes to Reduced Mortality in Sepsis Patients With Severe Respiratory Failure: A Retrospective Observational Study Using a Multicenter Dataset.

Background: Recombinant human-soluble thrombomodulin (rhTM) is a novel class therapeutic agent for managing disseminated intravascular coagulation. The progression of severe respiratory failure may be related to intra-alveolar coagulation/fibrinolytic disorders. We aimed to determine the efficacy of rhTM in treating sepsis patients with severe respiratory failure.

Methods: We performed a retrospective observational study using an existing dataset collected from 42 intensive care units (ICUs) in Japan. Of 3,195 patients with severe sepsis or septic shock from the dataset, we selected sepsis patients with severe respiratory failure, and compared patient outcomes based on the administration of rhTM (rhTM group and no rhTM group). Propensity score analysis was performed between the two groups. Outcomes of interest were ICU mortality, hospital mortality, and ventilator-free days (VFDs).

Results: In this study, 1,180 patients (rhTM, n = 356; no rhTM, n = 824) were analyzed. After adjusting for baseline imbalances with propensity score matching, the survival-time analysis revealed a significant difference between the two groups (hazard ratio, 0.654; 95% confidence interval, 0.439-0.974, P = 0.03). ICU mortality was lower in the rhTM group (rhTM: 22.1% [33/149] vs. no rhTM: 36.2% [54/149], P = 0.01). Hospital mortality was also lower in the rhTM group (35.6% [53/149] vs. 49.7% [74/149], P = 0.02). VFDs trended to be higher in the rhTM group than the no rhTM group (12.8 ± 10.1 days vs. 10.6 ± 10.6 days, P = 0.09).

Conclusions: Administration of rhTM was positively correlated with a reduction in mortality in sepsis patients with severe respiratory failure.