The wind changed direction and the big river still flows: from EUPHRATES to TIGRIS

Toshiaki Iba,David J Klein

doi:10.1186/s40560-019-0386-0

Abstract

The overall result of the randomized controlled double-blinded trial for polymyxin B-immobilized fiber column on septic shock (EUPHRATES trial) was disappointing. However, post hoc analysis showed benefits for patients with certain Endotoxin Activity Assay (EAA) levels. Thus, the study will be repeated, and the data will be added to the former trial. Using a precision medicine approach, eligibility criteria have been modified in TIGRIS to include patients with MODS score > 9 and EAA levels between 0.60 and 0.89. We are currently feeling the change in the wind as the rivers continue to flow towards PMX therapy for endotoxemic septic shock.

Highlights

Main text Hemoperfusion using a polymyxin B-immobilized (PMX) fiber column (ToraymyxinTM) for septic shock was initiated in the 1980s
Since the efficacy has not been conclusive [3], a randomized controlled trial (RCT) ‘Evaluating the Use of Polymyxin B Hemoperfusion in a Randomized controlled trial of Adults Treated for Endotoxemia and Septic shock (EUPHRATES)’ was conducted in North America [4]
An amendment to the protocol was made after the interim analysis that suggested lack of effect in the patients with Multiple Organ Dysfunction Score (MODS) of 9 or less, and those patients were excluded thereafter

Summary

Introduction

Hemoperfusion using a polymyxin B-immobilized (PMX) fiber column (ToraymyxinTM) for septic shock was initiated in the 1980s. Since the efficacy has not been conclusive [3], a randomized controlled trial (RCT) ‘Evaluating the Use of Polymyxin B Hemoperfusion in a Randomized controlled trial of Adults Treated for Endotoxemia and Septic shock (EUPHRATES)’ was conducted in North America [4]. Patients with refractory shock and endotoxin activity assay (EAA) levels ≥ 0.6 were randomized to treatment with or without PMX hemoperfusion.

Results

Conclusion