Polymyxin B haemoadsorption associated with lower mortality in endotoxic septic shock patients

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The Lancet. Respiratory medicine Published May 2, 2026 Medically reviewed May 8, 2026 Study authors: Neyra Javier A, Legrand Matthieu, Tidswell Mark A, Al-Khafaji Ali, Galphin Claude, Rains Ronald, Dav… PubMed ↗ NCT03901807 ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider polymyxin B haemoadsorption for endotoxic septic shock, noting association not causation.

This phase 3 trial investigated the use of polymyxin B haemoadsorption in adults with endotoxic septic shock requiring vasopressors and exhibiting multiple organ dysfunction. The intervention involved two sessions of the procedure alongside standard care, compared against standard care alone in a randomized controlled setting across multiple US hospitals.

Results indicated a lower mortality rate in the polymyxin B group at both 28 and 90 days. The authors utilized a Bayesian framework to report a high probability of benefit for the intervention group. Safety data showed a higher rate of serious adverse events in the treatment arm, though specific tolerability issues were limited.

The study authors highlight that personnel were masked to treatment allocation despite the open-label nature of the trial. They emphasize that the findings represent an association rather than definitive causation. Consequently, the clinical relevance remains cautious, suggesting the procedure may be considered in specific endotoxic shock scenarios while acknowledging the need for further validation.

Study Details

Study typeRct

Sample sizen = 890

EvidenceLevel 2

Follow-up216.0 mo

PublishedMay 2026

PMID41887242

TrialNCT03901807

View Original Abstract ↓

BACKGROUND: Endotoxic septic shock, a subset of septic shock with high endotoxin activity and multiorgan failure, is associated with high risk of death. We sought to identify the effect of endotoxin removal from the blood with polymyxin B haemoadsorption on mortality. METHODS: We conducted an open-label, randomised, controlled, phase 3 trial at 19 US hospitals, enrolling adults (aged ≥18 years) with septic shock requiring vasopressors, with multiple organ dysfunction, and with endotoxin activity between 0·60 and 0·89 units. Patients were randomly assigned (2:1) to receive two sessions of polymyxin B plus standard of care or standard of care alone (control), with block randomisation stratified by site. Study personnel were masked to treatment allocation. Polymyxin B haemoadsorption was given via haemodialysis at a blood flow rate of 80-120 mL/min for 90-120 min per session, 22 h apart. The primary outcome was 28-day mortality in the intention-to-treat cohort. The safety cohort included all participants exposed to any amount of study treatment. Design and analysis followed a Bayesian framework, using a prior for the treatment effect based on a subgroup of the earlier EUPHRATES trial. 90-day mortality was the key secondary outcome. The trial was registered at ClinicalTrials.gov and is completed (NCT03901807). FINDINGS: Between Sept 30, 2019, and April 10, 2025, we screened 14 890 patients, of whom 157 were enrolled (106 assigned to polymyxin B and 51 to control; 66 [42%] women and 91 [58%] men). At 28 days, 41 (39%) patients in the polymyxin B group and 23 (45%) in the control group had died, yielding a posterior probability of benefit of 95·3% (APACHE-II adjusted odds ratio 0·67 [95% credible interval 0·39-1·08]). At 90 days, the posterior probability of benefit was 99·4% (0·54 [0·32-0·87]). Of 100 patients in the polymyxin B group assessed for safety, 30 (30%) had a serious adverse event compared with 11 (22%) of 51 patients in the control group (difference -8 percentage points [95% CI -22 to 6]). Two (2%) serious adverse events in the polymyxin B group were treatment-related, one related to polymyxin B and one to catheter placement. INTERPRETATION: In patients with endotoxic septic shock defined by high endotoxin activity and multiorgan failure, polymyxin B haemoadsorption was associated with a high probability of lower mortality at 28 days and 90 days. FUNDING: Spectral Medical.