This randomised controlled trial by Hagiwara et al was published in BMJ Open in late 2016 and so is available full text via this link.
Objective To determine whether treatment with recombinant human thrombomodulin (rhTM) increases survival among patients with severe septic-induced disseminated intravascular coagulation (DIC).
Design Single-centre, open-label, randomised controlled trial.
Setting Single tertiary hospital.
Participant 92 patients with severe septic-induced DIC.
Interventions Patients with DIC scores ≥4, as defined by the Japanese Association of Acute Medicine, were diagnosed with DIC. The envelope method was used for randomisation. The treatment group (rhTM group, n=47) was intravenously treated with rhTM within 24 hours of admission (day 0), and the control group (n=45) did not receive any anticoagulants, except in cases of deep venous thrombosis and pulmonary embolism.
Primary and secondary measurements Data were collected on days 0 (admission), 1, 2, 3, 5, 7 and 10. The primary outcome was survival at 28 and 90 days. The secondary end points comprised changes in DIC scores, platelet counts, D-dimer, antithrombin III and C reactive protein levels, and Sequential Organ Failure Assessment (SOFA) scores. All analyses were conducted on an intent-to-treat basis.
Main results The 28-day survival rates were 84% and 83% in the control and rhTM groups, respectively (p=0.745, log-rank test). The 90-day survival rates were 73% and 72% in the control and rhTM groups, respectively (p=0.94, log-rank test). Meanwhile, the rates of recovery from DIC (<4) were significantly higher in the rhTM group than in the control group (p=0.001, log-rank test). Relative change from baseline of D-dimer levels was significantly lower in the rhTM group than in the control group, on days 3 and 5. Conclusions rhTM treatment decreased D-dimer levels and facilitated DIC recovery in patients with severe septic-induced DIC. However, the treatment did not improve survival in this cohort.