Efficacy and safety of recombinant human soluble thrombomodulin in patients with sepsis‐associated coagulopathy: A systematic review and meta‐analysis

Abstract

BackgroundThe efficacy and safety of recombinant human soluble thrombomodulin (rhsTM) have not been definitively proven. The effects may depend on the presence of sepsis‐associated coagulopathy (SAC). ObjectivesThe aim of this systematic review and meta‐analysis was to evaluate the efficacy and safety of rhsTM in patients with SAC defined by high international normalized ratio and low platelet count. Patients/MethodsEMBASE, MEDLINE, CENTRAL, and clinicaltrial.gov were searched for randomized controlled trials (RCTs) comparing rhsTM with placebo or no treatment in patients with sepsis. The efficacy outcome was 28‐day mortality, and the safety outcome was major bleeding. ResultsWe included 3 RCTs with a total of 1633 patients. Twenty‐eight‐day mortality was higher in patients with SAC compared with those without SAC (risk ratio [RR] 1.32; 95% confidence intervals [CI], 1.06‐1.64). rhsTM was associated with significantly lower 28‐day mortality compared with placebo or no treatment in patients with SAC (RR 0.80; 95% CI, 0.65‐0.98), but not in those without SAC (RR 1.17; 95% CI, 0.82‐1.67) nor in the whole study population (RR 0.88; 95% CI, 0.74‐1.04). There was no significant difference in major bleeding between rhsTM and controls in the whole population (RR 1.25; 95% CI, 0.80‐1.96), patients with SAC (RR 0.94; 95% CI, 0.45‐1.95), and those without SAC (RR 2.26; 95% CI, 0.95‐5.35). ConclusionsIn patients with sepsis, SAC is associated with higher 28‐day mortality. The administration of rhsTM reduced 28‐day mortality in patients with SAC, but not in those without SAC.