Polymyxin B haemoadsorption in endotoxic septic shock (Tigris): a multicentre, open-label, Bayesian, randomised, controlled, phase 3 trial.

Summary

In a 19-center Bayesian phase 3 randomized trial of patients with biomarker-defined endotoxic septic shock, two sessions of polymyxin B hemoadsorption showed a high posterior probability of reducing mortality at 28 and 90 days versus standard care. Safety was acceptable overall, with two treatment-related serious adverse events reported.

Key Findings

• At 28 days, mortality was 39% with polymyxin B versus 45% with control; posterior probability of benefit 95.3% (APACHE-II adjusted OR 0.67; 95% CrI 0.39–1.08).
• At 90 days, posterior probability of benefit was 99.4% (adjusted OR 0.54; 95% CrI 0.32–0.87).
• Serious adverse events occurred in 30% (polymyxin B) vs 22% (control); two were treatment-related.
• Treatment consisted of two hemoadsorption sessions (90–120 min, 22 h apart) at 80–120 mL/min blood flow.

Clinical Implications

For vasopressor-dependent septic shock with high endotoxin activity (0.60–0.89) and multiorgan failure, centers with hemoperfusion capability may consider polymyxin B hemoadsorption as an adjunct to standard care, while weighing logistics, resource needs, and safety monitoring. Adoption should be accompanied by protocols for patient selection and outcome auditing.

Limitations

• Open-label design and modest sample size (n=157) limit precision; 28-day credible interval crossed 1.0.
• Generalizability beyond US centers and cost-effectiveness remain untested.

Future Directions

Undertake larger pragmatic RCTs with health-economic evaluation, refine patient selection algorithms (e.g., dynamic endotoxin trends), and compare hemoadsorption timing/‘dose’ strategies.