RPSGL-Ig for improvement of early liver allograft function: A double-blind, placebo-controlled, single-center phase II study

R. W. Busuttil, G. S. Lipshutz, J. W. Kupiec-Weglinski, S. Ponthieux, D. W. Gjertson, C. Cheadle, T. Watkins, E. Ehrlich, E. Katz, E. C. Squiers, H. Rabb, S. Hemmerich

Research output: Contribution to journalArticlepeer-review

Abstract

The selectin antagonist known as recombinant P-selectin glycoprotein ligand IgG (rPSGL-Ig) blocks leukocyte adhesion and protects against transplantation ischemia reperfusion injury (IRI) in animal models. This randomized (1:1) single-center double-blind 47-patient phase 2 study with 6-month follow-up assessed rPSGL-Ig's safety and impact on early graft function at 1 mg/kg systemic dose with pretransplant allograft ex vivo treatment in deceased-donor liver transplant recipients. Safety was assessed in all patients, whereas efficacy was assessed in a prospectively defined per-protocol patient set (PP) by peak serum transaminase (TA) and bilirubin values, and normalization thereof. In PP patients, the incidence of poor early graft function (defined as peak TA >2500 U/L or bilirubin >10 mg/dL), average peak liver enzymes and bilirubin, normalization thereof and duration of primary and total hospitalization trended consistently lower in the rPSGL-Ig group compared to placebo. In patients with donor risk index above study-average, normalization of aspartate aminotransferase was significantly improved in the rPSGL-Ig group (p < 0.03). rPSGL-Ig treatment blunted postreperfusion induction versus placebo of IRI biomarker IP-10 (p < 0.1) and augmented cytoprotective IL-10 (p < 0.05). This is the first clinical trial of an adhesion molecule antagonist to demonstrate a beneficial effect on liver transplantation IRI and supported by therapeutic modulation of two hepatic IRI biomarkers.

Original languageEnglish (US)
Pages (from-to)786-797
Number of pages12
JournalAmerican Journal of Transplantation
Volume11
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • Clinical trial
  • ischemia reperfusion injury
  • liver transplantation
  • selectin antagonist

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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