Protein Kinase C Inhibitor Sotrastaurin in De Novo Liver Transplant Recipients: A Randomized Phase II Trial.
Pascher A, Simone De P, et al.American Journal of Transplantation. 2015 May; 15(5): 1283-92
Aims
To evaluate the efficacy and safety of sotrastaurin (STN) based regimens and to assess if STN based immunosuppression can minimize renal impairment in de novo liver transplant recipients.
Interventions
STN 200 mg/standard TAC (n=50) versus STN 200 mg/reduced TAC (n=52) versus STN 300 mg/reduced TAC (n=50) versus MMF/standard TAC (n=52).
Participants
204 de novo liver transplant recipients.
Outcomes
The primary end point was a composite efficacy end point of treated biopsy-proven acute rejection episodes of Banff grade 1, graft loss, or death. Safety endpoint was renal function at Month 12. Safety was assessed on the incidence of new onset diabetes, infections and malignancy.
Follow-up
24 months.
CET Conclusions
The efficacy and safety of the protein kinase C inhibitor sotrastaurin was tested in a four arm trial with tacrolimus in standard or reduced dose, while the protein kinase inhibitor was given in three doses. The control arm received MMF and standard tacrolimus and all groups received steroids. 204 patients were randomised in the trial and there was a higher efficacy failure rate in the three arms receiving the protein kinase C inhibitor compared to the control arm, and there were more adverse events in the three sotrastaurin arms. There was perhaps just a suggestion of better renal function in the STN groups compared to the control arm. The trial was terminated prematurely when the trials in kidney transplantation also showed a lack of efficacy.
Data analysis
Per protocol analysis
Trial registration
ClinicalTrials.gov - NCT01128335.