title: rPSGL-Ig for improvement of early liver allograft function: a double-blind, placebo-controlled, single-center phase II study.
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.
authors.affiliation: Dumont UCLA Transplant Center, Los Angeles, CA, USA. magnin@ccf.org
authors.forename: R W
authors.initials: RW
authors.lastname: Busuttil
authors.forename: G S
authors.initials: GS
authors.lastname: Lipshutz
authors.forename: J W
authors.initials: JW
authors.lastname: Kupiec-Weglinski
authors.forename: S
authors.initials: S
authors.lastname: Ponthieux
authors.forename: D W
authors.initials: DW
authors.lastname: Gjertson
authors.forename: C
authors.initials: C
authors.lastname: Cheadle
authors.forename: T
authors.initials: T
authors.lastname: Watkins
authors.forename: E
authors.initials: E
authors.lastname: Ehrlich
authors.forename: E
authors.initials: E
authors.lastname: Katz
authors.forename: E C
authors.initials: EC
authors.lastname: Squiers
authors.forename: H
authors.initials: H
authors.lastname: Rabb
authors.forename: S
authors.initials: S
authors.lastname: Hemmerich
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000517:prevention & control*; D014184:Transplantation, Homologous
chemical_list: D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D011994:Recombinant Proteins; D016753:Interleukin-10