Plasma as endothelial rescue in septic shock: A randomized, phase 2a pilot trial

Niels E. Clausen*, Christian S. Meyhoff, Hanne H. Henriksen, Anne Lindhardt, Frank C. Pott, Thomas Bech Lunen, Mikkel Gybel-Brask, Theis Lange, Pär I. Johansson, Jakob Stensballe

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstract

Background
Septic shock is associated with high morbidity and mortality, the endothelium plays an important role. Crystalloids is standard of care to maintain intravascular volume. Plasma is associated with improved endothelial integrity and restoration of the glycocalyx layer. We evaluated the efficacy and safety aspects of cell-free and pathogen inactivated pooled plasma (OctaplasLG®) as resuscitation in septic shock patients.

Study Design and Methods
This randomized, investigator-initiated phase IIa trial ran at a Danish single center intensive care unit, from 2017 to 2019. Patients were 18 years of age or older with septic shock and randomized to fluid optimization with OctaplasLG® or Ringer-acetate in the first 24 h. The primary endpoints were changes in biomarkers indicative of endothelial activation, damage, and microvascular perfusion from baseline to 24 h. Safety events and mortality were assessed during 90 days.

Results
Forty-four patients were randomized, 20 to OctaplasLG versus 24 to Ringer-acetate. The median age was 69, and 55% were men. Median Sequential Organ Failure Assessment score was 13. Baseline differences favoring the Ringer-acetate group were observed. The OctaplasLG® group was resuscitated with 740 mL plasma and the Ringer-acetate group with 841 mL crystalloids. There was no significant change in the microvascular perfusion or five biomarkers except VEGFR1 change, which was higher in patients receiving OctaplasLG® 0.12(SD 0.37) versus Ringer-acetate −0.24 (SD 0.39), with mean difference 0.36 (95% CI, 0.13–0.59, p = .003) in favor of Ringer-acetate.

Discussion
This study found that fluid resuscitation with OctaplasLG® in critically ill septic shock patients is feasible. Baseline confounding prevented assessment of the potential effect of OctaplasLG®.
OriginalsprogEngelsk
TidsskriftTransfusion
Vol/bind64
Udgave nummer9
Sider (fra-til)1653-1661
Antal sider9
ISSN0041-1132
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
The research project is investigator\u2010initiated by the trial sponsor P\u00E4r I. Johansson. This investigator\u2010initiated trial was funded by internal departmental funds and an unrestricted research grant (EUR 271,000) from Octapharma AG, the manufacturer of OctaplasLG\u00AE\u00AE, paid to and administered by Copenhagen University Hospital, Rigshospitalet, to support the execution of the trial covering expenses to assisting staff, on\u2010call research assistants, blood samples and laboratory analyses, etc. Octapharma AG also supplied the investigational product of the trial free of charge (estimated 200\u2009units of OctaplasLG\u00AE\u00AE amounting to EUR 22,000). The amount is paid to Rigshospitalet and is administered by Rigshospitalet, according to a contract between Rigshospitalet and Octapharma AG. None of the authors involved have received personal income from Octapharma AG, have shares, or financial interests in Octapharma AG, and Octapharma AG had no role in the design of this study, its execution, analysis, interpretation of the data, writing of the paper, or decision to submit results. Neither patients nor health personnel will receive any remuneration from participating in the trial. Octapharma AG has no influence on the design, the conduct, or the results of the trial.

Publisher Copyright:
© 2024 AABB.

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