Kazuma Yamakawa1, Shuhei Murao1, Morio Aihara2. 1. Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan. 2. Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki University, Hirosaki, Japan.
Abstract
BACKGROUND: Clinical effectiveness of recombinant human soluble thrombomodulin (rhTM) in sepsis or sepsis-induced coagulopathy remains a matter of dispute. Recently, the Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin (SCARLET) trial, the latest multinational multi-centre phase III randomized controlled trial, was completed. OBJECTIVE: This article assesses the benefits and harms of rhTM therapy in sepsis-induced coagulopathy by updating our previous systematic review. METHODS: We performed a systematic review and meta-analysis of rhTM therapy for sepsis-induced coagulopathy in randomized controlled trials. All-cause 28-day mortality as efficacy and serious bleeding complications as the adverse effect were measured as primary outcomes. We assessed the certainty of a body of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: We analysed five trials enrolling 1,762 patients. Approximately 13% reduction in the risk of mortality was observed in the rhTM group, but the difference was not significant (relative risk, 0.87; 95% confidence interval, 0.74-1.03; p = 0.10; I 2 = 0%). Risk of serious bleeding complications did not increase with rhTM administration. We judged the certainty of evidence as moderate for mortality and low for serious bleeding. Trial sequential analysis indicated that only 42.0% of the required information size is actually available at this stage to reject or accept low risk-of-bias trials examining the anticipated effect for all-cause mortality. CONCLUSION: Even in this updated review including the latest SCARLET trial, we currently cannot make any declarative judgments about the beneficial effects of rhTM in sepsis-induced coagulopathy, although some favourable effects were suggested. Georg Thieme Verlag KG Stuttgart · New York.
BACKGROUND: Clinical effectiveness of recombinant human soluble thrombomodulin (rhTM) in sepsis or sepsis-induced coagulopathy remains a matter of dispute. Recently, the Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin (SCARLET) trial, the latest multinational multi-centre phase III randomized controlled trial, was completed. OBJECTIVE: This article assesses the benefits and harms of rhTM therapy in sepsis-induced coagulopathy by updating our previous systematic review. METHODS: We performed a systematic review and meta-analysis of rhTM therapy for sepsis-induced coagulopathy in randomized controlled trials. All-cause 28-day mortality as efficacy and serious bleeding complications as the adverse effect were measured as primary outcomes. We assessed the certainty of a body of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: We analysed five trials enrolling 1,762 patients. Approximately 13% reduction in the risk of mortality was observed in the rhTM group, but the difference was not significant (relative risk, 0.87; 95% confidence interval, 0.74-1.03; p = 0.10; I 2 = 0%). Risk of serious bleeding complications did not increase with rhTM administration. We judged the certainty of evidence as moderate for mortality and low for serious bleeding. Trial sequential analysis indicated that only 42.0% of the required information size is actually available at this stage to reject or accept low risk-of-bias trials examining the anticipated effect for all-cause mortality. CONCLUSION: Even in this updated review including the latest SCARLET trial, we currently cannot make any declarative judgments about the beneficial effects of rhTM in sepsis-induced coagulopathy, although some favourable effects were suggested. Georg Thieme Verlag KG Stuttgart · New York.