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

NCT00149890 | Completed Phase 3 Results

• 1 other identifier: CCHI621ADE04
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Transplantation; Infection

Keywords

pediatric; liver transplantation; Simulect; Basiliximab; ciclosporin microemulsion; steroid reduction; pediatric liver transplantation

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

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

  3 months

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

  3 and 6 months

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

  3 months and 6 months

• Number of Participants With Bacterial, Viral and Fungal Infections During Six Months

  6 months

• Time of Onset of a First Biopsy Proven Acute Rejection

  6 months

Study Arms (2)

With Intraoperative Steroids

EXPERIMENTAL

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.

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

Without Intraoperative Steroids

ACTIVE COMPARATOR

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.

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

Interventions

Basiliximab DRUG

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.

Also known as: Simulect®

With Intraoperative Steroids; Without Intraoperative Steroids

Cyclosporine/cyclosporine microemulsion DRUG

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.

Also known as: Sandimmun®/Sandimmun® Optoral

With Intraoperative Steroids; Without Intraoperative Steroids

Steroid DRUG

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).

With Intraoperative Steroids; Without Intraoperative Steroids

Eligibility Criteria

• Age: Up to 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Pediatric patients undergoing primary orthotopic liver transplantation (whole organ or split liver or reduced size)
• Cadaveric or living donor (related or unrelated)

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Novartis: lead

Study Sites (1)

Novartis Investigational Site

Various Cities, Germany

Location

MeSH Terms

Conditions

Infections

Interventions

Basiliximab; Cyclosporine; Steroids

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Fused-Ring Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis

  Novartis

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 6, 2005
• First Posted: September 8, 2005
• Study Start: March 1, 2004
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: September 22, 2011
• Results First Posted: September 22, 2011

Record last verified: 2011-08

Locations

DE (1)