title: Protein kinase C inhibitor sotrastaurin in de novo liver transplant recipients: a randomized phase II trial.
abstract: Efficacy and safety of protein kinase C inhibitor sotrastaurin (STN) with tacrolimus (TAC) was assessed in a 24-month, multicenter, phase II study in de novo liver transplant recipients. A total of 204 patients were randomized (1:1:1:1) to STN 200 mg b.i.d. + standard-exposure TAC (n = 50) or reduced-exposure TAC (n = 52), STN 300 mg b.i.d. + reduced-exposure TAC (n = 50), or mycophenolate mofetil (MMF) 1 g b.i.d. + standard-exposure TAC (control, n = 52); all with steroids. Owing to premature study termination, treatment comparisons were only conducted for Month 6. At Month 6, composite efficacy failure rates (treated biopsy-proven acute rejection episodes of Banff grade ≥1, graft loss, or death) were 25.0%, 16.5%, 20.9% and 15.9% for STN 200 mg + standard TAC, STN 200 mg + reduced TAC, STN 300 mg + reduced TAC and control groups, respectively. Median estimated glomerular filtration rates were 84.0, 83.3, 81.1 and 75.3 mL/min/1.73 m(2), respectively. Gastrointestinal events (constipation, diarrhea, and nausea), infection, and tachycardia were more frequent in STN groups. More patients in STN groups experienced serious adverse events compared with the control group (62.3-70.8% vs. 51.9%). STN-based regimens were associated with a higher efficacy failure rate and higher incidence of adverse events with no significant difference in renal function between the groups.
authors: Charité - Universitaetsmedizin Berlin, Berlin, Germany.
authors: A
authors: A
authors: Pascher
authors: P
authors: P
authors: De Simone
authors: J
authors: J
authors: Pratschke
authors: E
authors: E
authors: Salamé
authors: J
authors: J
authors: Pirenne
authors: H
authors: H
authors: Isoneimi
authors: M
authors: M
authors: Bijarnia
authors: I
authors: I
authors: Krishnan
authors: J
authors: J
authors: Klupp
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation; D017093:Liver Failure / Q000401:mortality / Q000601:surgery*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000008:administration & dosage*; D011799:Quinazolines / Q000008:administration & dosage*; D016559:Tacrolimus / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D011758:Pyrroles; D011799:Quinazolines; C543528:sotrastaurin; D011493:Protein Kinase C; D016559:Tacrolimus
keywords: Clinical research; hepatology; immunemodulation; immunosuppression; liver transplantation; practice