Polymyxin B haemoadsorption in endotoxic septic shock (Tigris): a multicentre, open-label, Bayesian, randomised,...

Area of Science:

• Critical Care Medicine
• Nephrology
• Infectious Diseases

Background:

• Endotoxic septic shock, characterized by high endotoxin activity and multiorgan failure, presents a significant mortality risk.
• Polymyxin B haemoadsorption is an investigational therapy aimed at removing endotoxins from the blood.

Purpose of the Study:

• To evaluate the efficacy of polymyxin B haemoadsorption in reducing mortality among patients with endotoxic septic shock.
• To assess the safety profile of polymyxin B haemoadsorption in this patient population.

Main Methods:

• An open-label, randomized, controlled, phase 3 trial was conducted across 19 US hospitals.
• 157 adult patients with septic shock, multiple organ dysfunction, and high endotoxin activity were enrolled and randomized (2:1) to receive polymyxin B haemoadsorption plus standard care or standard care alone.
• The primary outcome was 28-day mortality, with 90-day mortality as a key secondary outcome, analyzed within a Bayesian framework.

Main Results:

• At 28 days, mortality was 39% in the polymyxin B group versus 45% in the control group, with a 95.3% posterior probability of benefit.
• At 90 days, the posterior probability of benefit for polymyxin B haemoadsorption was 99.4%.
• Serious adverse events occurred in 30% of the polymyxin B group compared to 22% in the control group, with two treatment-related serious adverse events in the polymyxin B arm.

Conclusions:

• Polymyxin B haemoadsorption demonstrated a high probability of lowering 28-day and 90-day mortality in patients with endotoxic septic shock.
• The therapy appears to be a promising intervention for this high-risk patient group, warranting further consideration in clinical practice.