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Abstract: TH-PO1188

Effect of Polymyxin B Hemoadsorption on Mortality in Patients with Endotoxic Septic Shock: The TIGRIS Trial

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Neyra, Javier A., The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Legrand, Matthieu, University of California San Francisco, San Francisco, California, United States
  • Tomlinson, George, University of Toronto, Toronto, Ontario, Canada
  • Kellum, John A., University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Group or Team Name

  • On behalf of the TIGRIS Investigators.
Background

Despite multiple trials and years of clinical use, evidence for effectiveness of polymyxin B hemoadsorption (PMX) on mortality in endotoxic septic shock (ESS) is inconclusive.

Methods

We sought to determine the probability that PMX reduces mortality at 28 and 90 days compared to standard of care for patients with ESS defined by endotoxin activity ≥0.6 but <0.9 units plus multiple organ failure. Tigris was a 19-center randomized trial in the US using a Bayesian analysis with an informative prior. Subjects were randomized 2:1 to receive PMX administered twice, for 2 hours each, using an extracorporeal veno-venous circuit at 100 ml/min, or standard of care. Mortality was assessed at 28 days (primary endpoint) and 90 days (key secondary endpoint). The treatment effect was estimated by the odds ratio (OR) comparing PMX to control, adjusting for the baseline APACHE II in a logistic regression model. The primary analysis used an informative normal prior distribution on the APACHE II-adjusted log-OR for PMX based on a discounted (down to 75%) estimate from logistic regression in a sample of 179 patients from the EUPHRATES trial with ESS.

Results

The final analysis included 157 patients from Tigris. Mortality at 28 days was 41/106 (38.7%) with PMX compared to 23/51 (45.1%) with standard of care alone. We found a 95.3% posterior probability that PMX is beneficial at 28 days compared to standard of care alone (OR with 95% credible interval: 0.67 (0.39, 1.08)). At 90 days mortality was 46/106 (43.4%) with PMX compared to 31/51 (60.8%) with standard of care alone and a posterior probability of benefit of 99.4% (OR: 0.54 (0.32, 0.87)). The unadjusted absolute risk reduction (ARR) from the posterior distribution was 8.3% [-2.1%, 19.7%] at 28 days, posterior probability of ARR >0, 92.3%. At 90 days the ARR was 12.3% [0.76%, 23.7%], posterior probability of ARR >0, 98.3%. The resultant number needed to treat to save one life was 12 at 28 days and 8 at 90 days.

Conclusion

A mortality benefit from PMX treatment was observed for patients with ESS.

Funding

  • Commercial Support – Spectral Medical

Digital Object Identifier (DOI)