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

Novartis77 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Liver Transplantation Infection

Interventions

Cyclosporine/cyclosporine microemulsionDRUG

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.

SteroidDRUG

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).

Eligibility

Sex: ALLMax age: 16 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Number of Participants With at Least One Biopsy Proven Acute Rejection (BPAR) Episode, Graft Loss or Death Within the First Three Months Post-transplantation

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.

Time frame: 3 months after treatment

Secondary Outcomes

Number of Participants With Biopsy Proven Acute Rejection (BPAR) Episodes Within the First Three 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.

Time frame: 3 months

Number of Participants With Steroid Resistant Rejection Episodes Within Three and Six 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.

Time frame: 3 and 6 months

Percentage of Participants Experiencing Death or Graft Loss Within Three and Six Months After Transplantation

Graft loss is defined as being listed for a re-transplantation.

Time frame: 3 months and 6 months

Number of Participants With Bacterial, Viral and Fungal Infections During Six 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 frame: 6 months

Time of Onset of a First Biopsy Proven Acute Rejection

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 .