Skip to content

Advertisement

Volume 18 Supplement 2

Sepsis 2014

  • Poster presentation
  • Open Access

Subgroup analysis of the lipid infusion and patient outcomes in sepsis trial (LIPOS) reveals benefit in a subgroup not treated with stress replacement doses of corticosteroids

  • TS Parker1, 2,
  • DM Levine1, 2,
  • BR Gordon1, 3 and
  • SD Saal1, 3
Critical Care201418(Suppl 2):P62

https://doi.org/10.1186/cc14065

Published: 3 December 2014

Keywords

Lower QuartileCholic AcidSerum Albumin LevelTreatment BenefitSodium Cholate

Introduction

Lipidose (formerly GR270773) is a protein-free phospholipid emulsion intended for the treatment of hospitalized patients with suspected or confirmed Gram-negative severe sepsis. Lipidose contains phosphatidylcholine, triglyceride and sodium cholate formulated to optimize delivery of the phospholipid component to the surface of high-density lipoprotein (HDL) and other lipoproteins, thereby enhancing the capacity of the patient's circulating lipoprotein pool to bind and neutralize microbial toxins. When Lipidose is infused into blood, the cholic acid is adsorbed onto serum albumin and the phospholipid selectively associates with lipoproteins. Bound and neutralized toxins are removed from the circulation by the liver and excreted along with the cholic acid into the bile. The LIPOS trial enrolled 1,400+ patients at 235 study centers in 31 countries to access Lipidose treatment at two dose levels. The LIPOS headline data presented only a small mortality benefit for the lower dose and no benefit from the higher dose [1]. A subgroup analysis was carried out to test the hypothesis of benefit in the subgroup with adequate liver function, using serum albumin levels as a measure of liver function, and adequate pre-existing HDL or total lipoprotein to accept phospholipid as predicted by the mechanism of action.

Methods

Albumin, cholesterol and HDL were measured in stored serum samples. The response to treatment and interactions with baseline covariates specified in LIPOS were tested after exclusion of subjects in the lowest biomarker quartiles (AlbTC25 and AlbHDL25).

Results

Subjects above the lowest quartile of albumin cleared Lipidose significantly faster than those in the lowest quartile (P < 0.003). Interactions between treatment and planned use of intravenous stress replacement doses of corticosteroids (IVCST) were found in the AlbTC25 and AlbHDL25 subgroups (P < 0.05). Exclusion of these subjects revealed strong relationships between treatment benefit and cholesterol or HDL that were used to select optimal biomarker thresholds. Requiring albumin ≥1.5 g/dl and either cholesterol ≥1 mM or HDL ≥0.5 mM selected 59% and 36%, respectively, of the LIPOS population. Treatment with Lipidose reduced mortality in these subgroups by 6.6% (P < 0.025) or 10.8% (P < 0.005) respectively. The treatment benefits persisted for at least 1 year.

Conclusion

A strong negative interaction with IVCST may have masked a significant treatment benefit in LIPOS. This interaction may be related to the ability of bile acids to slow clearance and raise concentrations of corticosteroids [2, 3]. Biomarkers can be used to select subjects with early severe septic shock responsive to treatment with Lipidose.

Declarations

Acknowledgements

TSP, DML, BRG and SDS are listed as inventors on patents filed by and/or assigned to Sepsicure, L.L.C.

Authors’ Affiliations

(1)
The Rogosin Institute, New York, USA
(2)
Department of Biochemistry, New York Presbyterian Hospital and Weill Cornell Medical College, New York, USA
(3)
Department of Medicine, New York Presbyterian Hospital and Weill Cornell Medical College, New York, USA

References

  1. Dellinger RP, Tomayko JF, Angus DC, Opal S, Cupo MA, McDermott S, Ducher A, Calandra T, Cohen J: Efficacy and safety of a phospholipid emulsion (GR270773) in Gram-negative severe sepsis: results of a phase II multicenter, randomized, placebo-controlled, dose-finding clinical trial. Crit Care Med 2009, 37: 2929-2938. 10.1097/CCM.0b013e3181b0266cView ArticlePubMedGoogle Scholar
  2. Boonen E, Vervenne H, Meersseman P, Andrew R, Mortier L, Declercq PE, Vanwijngaerden YM, Spriet I, Wouters PJ, Vander Perre S, et al.: Reduced cortisol metabolism during critical illness. N Engl J Med 2013, 368: 1477-1488. 10.1056/NEJMoa1214969View ArticlePubMedPubMed CentralGoogle Scholar
  3. Vanwijngaerden YM, Wauters J, Langouche L, Vander Perre S, Liddle C, Coulter S, Vanderborght S, Roskams T, Wilmer A, Van den Berghe G, et al.: Critical illness evokes elevated circulating bile acids related to altered hepatic transporter and nuclear receptor expression. Hepatology 2011, 54: 1741-1752. 10.1002/hep.24582View ArticlePubMedGoogle Scholar

Copyright

© Parker et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Advertisement