Efficacy and Safety of Basiliximab, Cyclosporine/Cyclosporine Microemulsion, and Steroids in Pediatric de Novo Liver Transplant Recipients Avoiding Intraoperative Steroids

Official Title: “A Multicenter, Open-label, Randomized, Two Arm Study to Investigate the Efficacy and Safety of a Therapy Avoiding Intraoperative Steroids in Combination With Basiliximab, Cyclosporine/Cyclosporine Microemulsion, and Steroids in Pediatric de Novo Liver Transplant Recipients”

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.

Intervention(s) in this Clinical Trial

• Drug: Basiliximab
  • 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.
• Drug: Cyclosporine/cyclosporine microemulsion
  • 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.
• Drug: Steroid
  • 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).

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: With Intraoperative Steroids
  • Intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft.
• Active Comparator: Without Intraoperative Steroids
  • No intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection.

Primary Measures

• Number of Participants With at Least One Biopsy Proven Acute Rejection (BPAR) Episode, Graft Loss or Death Within the First Three Months Post-transplantation
  • Time Frame: 3 months after treatment
    Safety Issue?: No

Secondary Measures

• Number of Participants With Biopsy Proven Acute Rejection (BPAR) Episodes Within the First Three Months
  • Time Frame: 3 months
    Safety Issue?: No
• Number of Participants With Steroid Resistant Rejection Episodes Within Three and Six Months
  • Time Frame: 3 and 6 months
    Safety Issue?: No
• Percentage of Participants Experiencing Death or Graft Loss Within Three and Six Months After Transplantation
  • Time Frame: 3 months and 6 months
    Safety Issue?: Yes
• Number of Participants With Bacterial, Viral and Fungal Infections During Six Months
  • Time Frame: 6 months
    Safety Issue?: Yes
• Time of Onset of a First Biopsy Proven Acute Rejection
  • Time Frame: 6 months
    Safety Issue?: No
• Percentage of Participants With Treatment Failure Within Three and Six Months
  • Time Frame: 3 and 6 months
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 16 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Novartis Industry

Overall Clinical Trial Officials and Contacts

Novartis Study Director Novartis  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00149890

Study ID Number: CCHI621ADE04

ClinicalTrials.gov Identifier: NCT00149890

Health Authority: Germany: Paul-Ehrlich-Institut