Protein kinase C inhibitor sotrastaurin in de novo liver transplant recipients: a randomized phase II trial
| Autor: | I. Krishnan, Andreas Pascher, J. Klupp, Johann Pratschke, E Salamé, H Isoneimi, M Bijarnia, Jacques Pirenne, P De Simone |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Graft Rejection Male medicine.medical_specialty Time Factors Nausea medicine.medical_treatment Biopsy Renal function Phases of clinical research Kaplan-Meier Estimate 030230 surgery Liver transplantation Gastroenterology Tacrolimus 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Immunology and Allergy Humans Pharmacology (medical) Pyrroles Enzyme Inhibitors Adverse effect Protein Kinase C Aged Transplantation business.industry Incidence Immunosuppression Hepatology Middle Aged Kidney Transplantation 3. Good health Surgery Liver Transplantation surgical procedures operative Treatment Outcome Quinazolines 030211 gastroenterology & hepatology Female medicine.symptom business Immunosuppressive Agents Liver Failure Glomerular Filtration Rate |
| Zdroj: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 15(5) |
| ISSN: | 1600-6143 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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