The TIGRIS trial suggested that biologically guided patient selection based on measurable endotoxemia may improve the use of polymyxin B hemoperfusion in patients with sepsis and potentially reversible organ dysfunction.
In a review of data on sepsis biology, endotoxin activity testing, previous polymyxin B hemoperfusion trials, and publicly available information from the TIGRIS trial, investigators examined whether an endotoxin- and severity-guided approach could improve patient selection for endotoxin-targeted therapy. The TIGRIS trial selected patients with endotoxin activity assay values of 0.60 to 0.89 and significant but potentially reversible organ dysfunction, defined by a Multiple Organ Dysfunction Score greater than 9 and/or a Sequential Organ Failure Assessment score greater than 11.
The investigators suggested that defining a therapeutic window based on endotoxin activity and organ dysfunction may explain why the TIGRIS trial identified a treatment signal comapred with the neutral findings of earlier trials involving polymyxin B hemoperfusion.
Previous sepsis trials targeting inflammatory, coagulation, and immune pathways may have failed because they enrolled biologically heterogeneous patient populations rather than patients whose disease biology matched the intervention. The investigators suggested that these findings supported a shift from syndromic enrollment toward biomarker-guided patient selection in future sepsis trials.
The investigators also highlighted the role of the endotoxin activity assay as a functional whole-blood test measureing circulating endotoxin bioactivity rather than endotoxin concentration. They noted that the assay demonstrated marked variability among patients and could help identify those in whom endotoxin remains a biologically relevant and potentially modifiable driver of organ dysfunction.
Beyond polymyxin B hemoperfusion, the investigators suggested that the principles demonstrated in the TIGRIS trial may have broader implications for precision medicine in sepsis. They proposed that future studies could incorporate biomarker-guided enrollment, adaptive trial designs, and dynamic assessment of biological phenotypes when evaluating anticoagulant, endothelial-protective, and immune-modulating therapies.
The investigators emphasized that the available evidence remains preliminary because the primary trial results have not yet been fully published in a peer-reviewed report.
The study had several limitations. Their interpretation of the TIGRIS trial was based largely on ClinicalTrials.gov entries and sponsor-reported summaries because a full peer-reviewed publication of the primary trial data is not yet available. Consequently, the reported treatment effect could not be independently verified and should be considered hypothesis-generating rather than confirmatory. Investigators also noted that broader implementation of endotoxin activity assay-guided therapy will depend on assay availability, standardization, cost-effectiveness, and integration into routine clinical practice.
"The TIGRIS trial may be viewed as a potentially informative step in sepsis therapeutics, suggesting that biologically guided therapy can succeed where syndrome-based approaches have failed," wrote lead study author Toshiaki Iba, of the Faculty of Medical Science at the Juntendo University in Japan, and colleagues.
The study authors reported no funding and declared no conflicts of interest.
