Effect of Targeted Polymyxin B Hemoperfusion on 28-Day Mortality in Patients With Septic Shock and Elevated Endotoxin Level: The EUPHRATES Randomized Clinical Trial | Critical Care Medicine | JAMA | JAMA Network
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In this randomized trial, polymyxin B hemoperfusion treatment plus conventional medical therapy did not reduce mortality at 28 days compared with sham treatment plus conventional medical therapy among patients with septic shock and high endotoxin activity. Phillip Dellinger, MD, MSc, of Cooper University Hospital and Cooper Medical School of Rowan University, Camden, New Jersey, presents findings from the EUPHRATES trial at the European Society of Intensive Care Medicine (ESICM) 31st Annual Congress, LIVES 2018, on October 24 in Paris. Used with permission.
Diederik Gommers, MD, PhD, of Erasmus University in Rotterdam, the Netherlands, comments on the findings of a trial reporting no difference in 28-day mortality among patients with septic shock and high endotoxin activity randomized to polymyxin B hemoperfusion treatment plus conventional medical therapy vs sham treatment plus conventional medical therapy. Comments were made at the European Society of Intensive Care Medicine (ESICM) 31st Annual Congress, LIVES 2018, on October 24 in Paris. Used with permission.
Original Investigation
Caring for the Critically Ill Patient
October 9, 2018

Effect of Targeted Polymyxin B Hemoperfusion on 28-Day Mortality in Patients With Septic Shock and Elevated Endotoxin Level: The EUPHRATES Randomized Clinical Trial

Author Affiliations
  • 1Cooper University Hospital and Cooper Medical School of Rowan University, Camden, New Jersey
  • 2Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
  • 3IRCCS Fondazione Policlinico Universitario A. Gemelli-Universitá Cattolica del Sacro Cuore, Rome Italy
  • 4Spectral Medical Inc, Toronto, Canada
  • 5St Michael’s Hospital, University of Toronto, Toronto, Canada
  • 6VA Pittsburgh Healthcare System and University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
JAMA. 2018;320(14):1455-1463. doi:10.1001/jama.2018.14618
Key Points

Question  Does polymyxin B hemoperfusion improve survival in patients with septic shock and high levels of endotoxin in the blood?

Findings  In this multicenter, randomized, clinical trial that included 450 adults with septic shock and high circulating endotoxin activity, polymyxin B hemoperfusion compared with sham hemoperfusion did not significantly decrease 28-day mortality, 37.7% vs 34.5%, respectively.

Meaning  Polymyxin B hemoperfusion was not effective in reducing mortality in septic shock.

Abstract

Importance  Polymyxin B hemoperfusion reduces blood endotoxin levels in sepsis. Endotoxin activity can be measured in blood with a rapid assay. Treating patients with septic shock and elevated endotoxin activity using polymyxin B hemoperfusion may improve clinical outcomes.

Objective  To test whether adding polymyxin B hemoperfusion to conventional medical therapy improves survival compared with conventional therapy alone among patients with septic shock and high endotoxin activity.

Design, Setting, and Participants  Multicenter, randomized clinical trial involving 450 adult critically ill patients with septic shock and an endotoxin activity assay level of 0.60 or higher enrolled between September 2010 and June 2016 at 55 tertiary hospitals in North America. Last follow-up was June 2017.

Interventions  Two polymyxin B hemoperfusion treatments (90-120 minutes) plus standard therapy completed within 24 hours of enrollment (n = 224 patients) or sham hemoperfusion plus standard therapy (n = 226 patients).

Main Outcomes and Measures  The primary outcome was mortality at 28 days among all patients randomized (all participants) and among patients randomized with a multiple organ dysfunction score (MODS) of more than 9.

Results  Among 450 eligible enrolled patients (mean age, 59.8 years; 177 [39.3%] women; mean APACHE II score 29.4 [range, 0-71 with higher scores indicating greater severity), 449 (99.8%) completed the study. Polymyxin B hemoperfusion was not associated with a significant difference in mortality at 28 days among all participants (treatment group, 84 of 223 [37.7%] vs sham group 78 of 226 [34.5%]; risk difference [RD], 3.2%; 95% CI, −5.7% to 12.0%; relative risk [RR], 1.09; 95% CI, 0.85-1.39; P = .49) or in the population with a MODS of more than 9 (treatment group, 65 of 146 [44.5%] vs sham, 65 of 148 [43.9%]; RD, 0.6%; 95% CI, −10.8% to 11.9%; RR, 1.01; 95% CI, 0.78-1.31; P = .92). Overall, 264 serious adverse events were reported (65.1% treatment group vs 57.3% sham group). The most frequent serious adverse events were worsening of sepsis (10.8% treatment group vs 9.1% sham group) and worsening of septic shock (6.6% treatment group vs 7.7% sham group).

Conclusions and Relevance  Among patients with septic shock and high endotoxin activity, polymyxin B hemoperfusion treatment plus conventional medical therapy compared with sham treatment plus conventional medical therapy did not reduce mortality at 28 days.

Trial Registration  ClinicalTrials.gov Identifier: NCT01046669

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