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rPSGL‐Ig for Improvement of Early Liver Allograft Function: A Double‐Blind, Placebo‐Controlled, Single‐Center Phase II Study †
Author(s) -
Busuttil R. W.,
Lipshutz G. S.,
KupiecWeglinski J. W.,
Ponthieux S.,
Gjertson D. W.,
Cheadle C.,
Watkins T.,
Ehrlich E.,
Katz E.,
Squiers E. C.,
Rabb H.,
Hemmerich S.
Publication year - 2011
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2011.03441.x
Subject(s) - medicine , liver transplantation , bilirubin , gastroenterology , placebo , single center , transplantation , liver function , alanine transaminase , aspartate transaminase , transaminase , surgery , urology , pathology , biochemistry , chemistry , alternative medicine , alkaline phosphatase , enzyme
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.