TY - JOUR
T1 - RPSGL-Ig for improvement of early liver allograft function
T2 - A double-blind, placebo-controlled, single-center phase II study
AU - Busuttil, R. W.
AU - Lipshutz, G. S.
AU - Kupiec-Weglinski, J. W.
AU - Ponthieux, S.
AU - Gjertson, D. W.
AU - Cheadle, C.
AU - Watkins, T.
AU - Ehrlich, E.
AU - Katz, E.
AU - Squiers, E. C.
AU - Rabb, H.
AU - Hemmerich, S.
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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.
KW - Clinical trial
KW - ischemia reperfusion injury
KW - liver transplantation
KW - selectin antagonist
UR - http://www.scopus.com/inward/record.url?scp=79953244190&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953244190&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2011.03441.x
DO - 10.1111/j.1600-6143.2011.03441.x
M3 - Article
C2 - 21401865
AN - SCOPUS:79953244190
VL - 11
SP - 786
EP - 797
JO - American Journal of Transplantation
JF - American Journal of Transplantation
SN - 1600-6135
IS - 4
ER -