SCARLET
Trial question
What is the effect of recombinant human soluble thrombomodulin in patients with sepsis-associated coagulopathy?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
45.0% female
55.0% male
N = 800
800 patients (363 female, 437 male).
Inclusion criteria: ICU adult patients with sepsis-associated coagulopathy and concomitant cardiovascular and/or respiratory failure.
Key exclusion criteria: platelets < 30,000/ mm³, known allergy to ART-123 or any components of the drug product, history of head trauma, or other acute trauma with an increased risk of bleeding within 3 months.
Interventions
N=395 recombinant human soluble thrombomodulin (an intravenous bolus or a 15-minute infusion of 0.06 mg/kg with a maximum dose of 6 mg/day, once daily for 6 consecutive days).
N=405 placebo (matching placebo once daily for 6 consecutive days).
Primary outcome
All-cause mortality at day 28
26.8%
29.4%
29.4 %
22.0 %
14.7 %
7.3 %
0.0 %
Recombinant human soluble
thrombomodulin
Placebo
No significant
difference ↔
No significant difference in all-cause mortality at day 28 (26.8% vs. 29.4%; ARD -2.55, 95% CI -3.68 to 8.77).
Secondary outcomes
Borderline significant decrease in median plasma concentration of D-dimer at day 6 (1129.5 ng/mL vs. 1649 ng/mL; AD -519.5 ng/mL, 95% CI -1039.89 to 0.89).
Borderline significant decrease in median plasma concentration of prothrombin fragment F1.2 at day 6 (309.6 pmol/L vs. 393.2 pmol/L; AD -83.6 pmol/L, 95% CI -167.34 to 0.14).
Borderline significant decrease in median plasma concentration of thrombin-antithrombin complex at day 6 (5.2 ng/mL vs. 7.8 ng/mL; AD -2.6 ng/mL, 95% CI -5.2 to 0).
Safety outcomes
No significant differences in adverse events, serious adverse events, serious major bleeding event.
Conclusion
In ICU adult patients with sepsis-associated coagulopathy and concomitant cardiovascular and/or respiratory failure, recombinant human soluble thrombomodulin was not superior to placebo with respect to all-cause mortality at day 28.
Reference
Jean-Louis Vincent, Bruno Francois, Igor Zabolotskikh et al. Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy: The SCARLET Randomized Clinical Trial. JAMA. 2019 May 28;321(20):1993-2002.
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