title: Study protocol: a pilot study to determine the safety and efficacy of induction-therapy, de novo MPA and delayed mTOR-inhibition in liver transplant recipients with impaired renal function. PATRON-study.
abstract: BACKGROUND
  Patients undergoing liver transplantation with preexisting renal dysfunction are prone to further renal impairment with the early postoperative use of Calcineurin-inhibitors. However, there is only little scientific evidence for the safety and efficacy of de novo CNI free "bottom-up" regimens in patients with impaired renal function undergoing liver transplantation. This is a single-center study pilot-study (PATRON07) investigating safety and efficacy of CNI-free, "bottom-up" immunosuppressive (IS) strategy in patients undergoing liver transplantation (LT) with renal impairment prior to LT.
  
  
  METHODS
  Patients older than 18 years with renal impairment at the time of liver transplantation eGFR < 50 ml/min and/or serum creatinine levels > 1.5 mg/dL will be included. Patients in will receive a CNI-free combination therapy (basiliximab, MMF, steroids and delayed Sirolimus). Primary endpoint is the incidence of steroid resistant acute rejection within the first 30 days after LT. The study is designed as prospective two-step trial requiring a maximum of 29 patients. In the first step, 9 patients will be included. If 8 or more patients show no signs of biopsy proven steroid resistant rejection, additional 20 patients will be included. If in the second step a total of 27 or more patients reach the primary endpoint the regimen is regarded to be safe and efficient.
  
  
  CONCLUSIONS
  If a CNI-free-"bottom-up" IS strategy is safe and effective, this may be an innovative concept in contrast to classic top-down strategies that could improve the patient short and long-time renal function as well as overall complications and survival after LT. The results of PATRON07 may be the basis for a large multicenter RCT investigating the new "bottom-up" immunosuppressive strategy in patients with poor renal function prior to LT.http://www.clinicaltrials.gov-identifier: NCT00604357.
authors.affiliation: Department of Surgery, Regensburg University Hospital, Regensburg, Germany. andreas.schnitzbauer@klinik.uni-r.de
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Schnitzbauer
authors.forename: Marcus N
authors.initials: MN
authors.lastname: Scherer
authors.forename: Justine
authors.initials: J
authors.lastname: Rochon
authors.forename: Johannes
authors.initials: J
authors.lastname: Sothmann
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Farkas
authors.forename: Martin
authors.initials: M
authors.lastname: Loss
authors.forename: Edward K
authors.initials: EK
authors.lastname: Geissler
authors.forename: Aiman
authors.initials: A
authors.lastname: Obed
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000077552:Basiliximab; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016031:Liver Transplantation; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D018579:Patient Selection; D010865:Pilot Projects; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000503:physiopathology*; D012107:Research Design; D020123:Sirolimus / Q000627:therapeutic use; D013256:Steroids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D013256:Steroids; D000077552:Basiliximab; D009173:Mycophenolic Acid; D020123:Sirolimus