News: Endotoxin removal tied to lower mortality risk in septic shock subtype, trial finds

Blood purification using polymyxin B showed a mortality reduction signal in patients with septic shock and high endotoxin activity, researchers reported. In the phase III Tigris trial, 28-day mortality was numerically lower in patients receiving standard of care plus two sessions of polymyxin B hemoadsorption (39%) versus standard of care alone (45%), with a baseline-severity-adjusted odds ratio of 0.80.

The absolute difference in mortality in favor of the hemodialysis intervention reached 18% at 90 days. In patients with endotoxic septic shock, defined as high endotoxic activity with multiorgan failure, polymyxin B hemoadsorption was associated with lower mortality probability at 28 days and 90 days.

Endotoxic septic shock “represents a specific subtype of septic shock affecting about 10% of patients with sepsis, characterized by overwhelming endotoxin-driven inflammation, vascular dysfunction, and subsequent multiorgan failure,” said Tobias Schupp, MD, PhD, and colleagues at Heidelberg University. “Endotoxin activity, which can be measured by point-of-care assays, can contribute to a robust host-immune response and subsequent multiorgan failure with short-term mortality rates reaching 60%.”

Pharmaceutical approaches targeting endotoxin—a lipopolysaccharide of Gram-negative bacteria—in septic shock have not been shown to improve survival, they noted.

The open-label phase III Tigris trial occurred from 2019 to 2025 and enrolled adults with septic shock at 19 intensive care units (ICUs) in the United States. It randomized 106 to standard of care plus polymyxin B via hemodialysis and 51 to standard of care alone. Odds ratios for mortality were adjusted for baseline Acute Physiology and Chronic Health Evaluation (APACHE-II) scores.

Among the patients alive and in the ICU at 28 days, six out of the nine (67%) in the polymyxin B group survived to 90 days, compared with one of six (17%) control patients.

Schupp and co-authors concluded that the trial “might serve as an important signpost towards modern precision medicine, shaping the way for a promising therapeutic approach for a select subgroup of patients with septic shock, which warrants special attention in view of an overall very poor prognosis.”

Editor’s note: To read the full study, click here. To read the accompanying editorial, click here. To read additional coverage of this study from MedPage Today, click here.