A new article reports the findings of the Tigris trial investigating the efficacy and safety of polymyxin B haemoadsorption in patients with endotoxic septic shock (ESS). ESS is a severe subtype of septic shock characterised by high circulating endotoxin levels and multiorgan failure, and is associated with a high mortality rate. Given the absence of targeted therapies for sepsis and the recognised heterogeneity of the condition, the study evaluates whether removing endotoxin from the bloodstream using polymyxin B could improve survival outcomes in a biologically defined subgroup of patients.
The trial was conducted across 19 hospitals in the United States and enrolled adult patients with septic shock requiring vasopressors, evidence of multiorgan dysfunction, and endotoxin activity assay (EAA) values between 0.60 and 0.89 units. This range was selected based on prior evidence suggesting that it represents a treatable level of endotoxaemia. Participants were randomly assigned in a 2:1 ratio to receive either polymyxin B haemoadsorption plus standard of care (SOC) or SOC alone. The intervention consisted of two haemoadsorption sessions delivered via haemodialysis over 90–120 minutes each, approximately 22 hours apart.
The primary outcome was 28-day mortality. The key secondary outcome was 90-day mortality. Between September 2019 and April 2025, nearly 14,900 patients were screened, but only 157 met the strict inclusion criteria and were enrolled, highlighting the rarity of this specific endotype.
At 28 days, mortality was 39% in the polymyxin B group compared with 45% in the control group. Although the absolute difference was modest, Bayesian analysis yielded a 95.3% posterior probability that polymyxin B reduced mortality, with an adjusted odds ratio of 0.67. At 90 days, the effect was more pronounced: mortality reductions corresponded to a posterior probability of benefit of 99.4% and an odds ratio of 0.54. These findings suggest a stronger and more robust survival benefit over a longer time horizon.
Secondary analyses supported these results. The estimated absolute risk reduction was approximately 10.3% at 28 days and 15.5% at 90 days, corresponding to numbers needed to treat of 9.7 and 6.5, respectively. Survival analyses also indicated improved outcomes with polymyxin B, particularly at 90 days. Patients in the control group were more likely to remain in intensive care with ongoing organ dysfunction at day 28 and had poorer subsequent survival, suggesting that early resolution of organ failure may be a key mechanism underlying the treatment effect.
The study also evaluated safety outcomes. Rates of treatment-emergent adverse events were similar between groups. Serious adverse events occurred in 30% of patients receiving polymyxin B and 22% of controls, with only 2% deemed related to the intervention. These included one case of hypotension and one bleeding event related to catheter placement; both resolved without long-term consequences. Overall, the safety profile was considered acceptable and consistent with other extracorporeal therapies.
In conclusion, the Tigris trial demonstrates that polymyxin B haemoadsorption is associated with a high probability of reduced mortality in patients with endotoxic septic shock characterised by elevated endotoxin activity and multiorgan failure. The findings highlight the importance of biologically informed patient selection and suggest that targeting specific pathophysiological mechanisms may improve outcomes in sepsis. Further research is needed to optimise treatment strategies and validate these results in broader clinical settings.
Source: The Lancet Respiratory Medicine
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