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

Phase 3

Completed

Conditions: Liver Transplantation
Infection

Interventions: Drug: Basiliximab
Drug: Cyclosporine/cyclosporine microemulsion
Drug: Steroid

Registration Number: NCT00149890

Lead Sponsor: Novartis

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 77

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
With Intraoperative Steroids	Basiliximab	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.
With Intraoperative Steroids	Cyclosporine/cyclosporine microemulsion	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.
With Intraoperative Steroids	Steroid	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.
Without Intraoperative Steroids	Cyclosporine/cyclosporine microemulsion	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.
Without Intraoperative Steroids	Steroid	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.
Without Intraoperative Steroids	Basiliximab	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 Outcome Measures

Name	Time	Method
Number of Participants With at Least One Biopsy Proven Acute Rejection (BPAR) Episode, Graft Loss or Death Within the First Three Months Post-transplantation	3 months after treatment	Graft loss is defined as being listed for a re-transplantation. The analysis was based on the locally performed biopsy assessments. Generally, patients not experiencing a relevant event (i.e., acute rejection, graft loss or death) were censored with the last visit date.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Episodes Within the First Three Months	3 months	At biopsy of transplanted tissue sample, acute rejection has an onset 2-60 days after transplantation, with interstitial vascular endothelial cell swelling, interstitial accumulation of lymphocytes, plasma cells, immunoblasts, macrophages, neutrophils; tubular separation with edema/necrosis of tubular epithelium; swelling and vacuolization of the endothelial cells, vascular edema, bleeding and inflammation. Clinical signs and symptoms include malaise, fever, and hypertension.
Number of Participants With Steroid Resistant Rejection Episodes Within Three and Six Months	3 and 6 months	To evaluate the efficacy of a regimen with intraoperative versus without intraoperative steroids in combination with basiliximab, cyclosporine/cyclosporine microemulsion and steroids as measured by the incidence of steroid resistant rejection episodes within three and six months.
Percentage of Participants Experiencing Death or Graft Loss Within Three and Six Months After Transplantation	3 months and 6 months	Graft loss is defined as being listed for a re-transplantation.
Number of Participants With Bacterial, Viral and Fungal Infections During Six Months	6 months	To evaluate the safety of a regimen with intraoperative versus without intraoperative steroids in combination with basiliximab, cyclosporine/cyclosporine microemulsion and steroids as measured by the episodes of bacterial, viral and fungal infections during six months.
Time of Onset of a First Biopsy Proven Acute Rejection	6 months	Biopsied Tissue shows rejection at onset 2-60 days after transplantation, with interstitial vascular endothelial cell swelling, interstitial accumulation of lymphocytes, plasma cells, immunoblasts, macrophages, neutrophils; tubular separation with edema/necrosis of tubular epithelium; swelling and vacuolization of the endothelial cells, vascular edema, bleeding and inflammation. Clinical signs and symptoms include malaise, fever and hypertension .
Percentage of Participants With Treatment Failure Within Three and Six Months	3 and 6 months	To evaluate the proportion of patients with treatment failure treated with a therapy consisting of intraoperative versus without intraoperative steroids in combination with basiliximab, cyclosporine/cyclosporine microemulsion and steroids within three and six months.