Effect of Targeted Polymyxin B Hemoperfusion on 28-Day Mortality in Patients With Septic Shock and Elevated Endotoxin Level: The EUPHRATES Randomized Clinical Trial
Open accessAbstract
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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From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [481]
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- Authors
- Dellinger, R. P., Bagshaw, S. M., Antonelli, M., Foster, D. M., Klein, D. J., Marshall, J. C., Palevsky, P. M., Weisberg, L. S., Schorr, C. A., Trzeciak, S., Walker, P. M., & for the EUPHRATES Trial Investigators
- Affiliations
- Cooper University Hospital (US)
- University of Alberta (CA)
- Università Cattolica del Sacro Cuore (IT)
- Spectral Medical Inc, Toronto, Canada
- St. Michael's Hospital (CA)
- University of Pittsburgh (US)
- Corresponding author
- Dellinger, R. Phillip
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2018-10-09
- Volume
- 320
- Issue
- 14
- Pages
- 1455
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC6233793
- OpenAlex
- W2897735762
- Cited by
- 502
- References
- 25
- Citations by year
- 2026: 73 · 2025: 71 · 2024: 71 · 2023: 70 · 2022: 52 · 2021: 54 · 2020: 63 · 2019: 40 · 2018: 5 · 2015: 1
- FWCI
- 31.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion, other-oa)
- Funders
- University of Nebraska Medical Center
- Memorial Sloan-Kettering Cancer Center
- Cleveland Clinic
- University of Pittsburgh
- East Carolina University
- Thomas Jefferson University
- Temple University
- University of Alberta
- Medical Center, University of Pittsburgh
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- polymyxin B hemoperfusion, septic shock, endotoxin activity, endotoxemia, 28-day mortality, multiple organ failure, sepsis, critically ill patients, endotoxin activity assay, survival outcomes, sepsis treatment, APACHE II score, multiple organ dysfunction score, sepsis mortality
- MeSH terms
- Adult, Aged, Anti-Bacterial Agents, Endotoxins, Female, Humans, Male, Middle Aged, Polymyxin B, Shock, Septic, Survival Analysis, Hospital Mortality, APACHE
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