Efficacy and Safety of Basiliximab, Cyclosporine/Cyclosporine Microemulsion, and Steroids in Pediatric de Novo Liver Transplant Recipients Avoiding Intraoperative Steroids
Condition: Liver Transplantation; Infection
Intervention: Basiliximab; Cyclosporine/cyclosporine microemulsion; Steroid
Intervention description: Basiliximab (10 mg) was supplied as a lyophilisate in vials with ampoules of sterile water for injection (5 mL) and had to be given of 10 mg (body weight <35 kg) or 20 mg (body weight ≥35 kg) strength.; Cyclosporine/cyclosporine microemulsion had to be started with 100 mg/m²/day intravenous (i.v) (2x4h) for 7 days and was to be continued i.v. or orally from day 8 onwards as per center practice. During the 6 months treatment period Cyclosporine doses had to be adjusted according to Cyclosporine A (CsA)-trough levels.; Intravenous prednisolone (loading dose: 300 mg/m2, maximum 500 mg) had to be administered intraoperatively only in treatment arm 1 (day 0). The first dose of steroids in treatment arm 2 (day 0) had to be administered within 8 hours after reperfusion of the graft. Beginning from day 1 to day 6 doses of 15 mg/m2/day had to be given intravenously (i.v.) in both treatment arms. Then, the steroid doses (oral prednisone or its equivalent) were to be decreased from 10 mg/m²/day orally (day 7-13), to 7.5 mg/m²/day orally (day 14-30), to 4 mg/m²/day orally (until end of month 2), to 2.5 mg/m²/day orally (until end of month 3) and to 1 mg/m²/day orally (until end of month 6).
Intervention MeSH terms: Cyclosporine; Cyclosporins; Basiliximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 77.0
Sex: All
Maximum age: 16 Years
Healthy volunteers: No
Keywords: pediatric; liver transplantation; Simulect; Basiliximab; ciclosporin microemulsion; steroid reduction; pediatric liver transplantation

Summary:

      Systemic infection is still a major concern in young children with liver transplantation. The
      approach of this study is to reduce the risk of systemic infections by avoiding
      intraoperative steroids (another class of immunosuppressive drugs) given in combination with
      basiliximab, cyclosporine and steroids in pediatric de novo liver transplant recipients. The
      treatment is compared to the same treatment regimen including intraoperative steroids with
      respect to rejection episodes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pediatric patients undergoing primary orthotopic liver transplantation (whole organ or
             split liver or reduced size)

          -  Cadaveric or living donor (related or unrelated)

        Exclusion Criteria:

          -  Patients who are recipients of multiple solid organ transplants and/or who have
             previously received transplanted organs

          -  If cold ischemia time of the transplanted organ is >12 hours

          -  Auxiliary liver transplant recipients

          -  Fulminant hepatic failure

          -  Autoimmune hepatitis

          -  Primary sclerosing cholangitis

          -  Severe acute systemic infections

          -  Hepatitis B surface antigen/HCV/HIV positive

          -  Known contraindication to intravenous (i.v.) or per os (orally) (p.o.) cyclosporine or
             corticoids

          -  Non-ability to comply with the protocol

          -  Relevant abnormal physical or laboratory findings within 2 weeks of inclusion

          -  Relevant severe allergy, hypersensitivity to basiliximab or similar drugs

          -  History/presence of relevant malignancy

          -  Pregnancy/breastfeeding

          -  Use of any investigational or immunomodulatory/immunosuppressive drug within 4 weeks
             prior to transplantation.