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

Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00149890
• Other study ID #: CCHI621ADE04
• Status: Completed
• Phase: Phase 3
• First received: September 6, 2005
• Last updated: August 17, 2011
• Start date: March 2004
• Est. completion date: March 2009

Study information

• Verified date: August 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 16 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Infection
• Liver Transplantation

Intervention

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.
• 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.
• 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).

Locations

Country	Name	City	State
Germany	Novartis Investigational Site	Various Cities

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3 months after treatment	No
Secondary	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.	3 months	No
Secondary	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.	3 and 6 months	No
Secondary	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.	3 months and 6 months	Yes
Secondary	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.	6 months	Yes
Secondary	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	6 months	No
Secondary	Percentage of Participants With Treatment Failure Within Three and Six 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.	3 and 6 months	No