Preservation of Renal Function in Liver Transplant Recipients With Certican Therapy

Phase 3

Completed

Conditions: Liver Transplantation

Interventions: Drug: everolimus
Drug: basiliximab
Drug: CNI

Registration Number: NCT00378014

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The study is designed to show that everolimus initiation together with reduction and thereafter discontinuation of calcineurin inhibitor (CNI) will improve significantly renal function in de novo liver transplant recipients as compared to continuation of CNI-based treatment.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 276

Inclusion Criteria

Males or females 18 - 70 years old
Liver transplant recipient (living or deceased donor)
Patients in whom an allograft biopsy will not be contraindicated

Exclusion Criteria

Recipients of multiple solid organ transplants or patients that have already received a transplant in the past
HCV positive patients who need an active anti-viral treatment (HCV- positive patients without active antiviral treatment are allowed)
HIV positive patients
Patients who are breast feeding
Patients with a current severe systemic infection
Presence of any hypersensitivity to drugs similar to Certican® (e.g. macrolides)
Preexisting (i.e. not related to CNI-damage) renal dysfunction that, according to the judgment of the investigator, will not significantly improve after transplantation (i.e., for example, patients that are expected to have a cGFR below 50ml/min at 4 weeks post transplantation)
Patients that have received Simulect prior to this study.
Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Everolimus	CNI	Basiliximab plus everolimus-based immunosuppressive regimen following the reduction and cessation of initial CNI regimen plus optional steroids according to local best practice
Calcineurin Inhibitor (CNI)	CNI	Basiliximab plus CNI-based immunosuppressive regimen according to local best practice plus optional steroids according to local best practice
Calcineurin Inhibitor (CNI)	everolimus	Basiliximab plus CNI-based immunosuppressive regimen according to local best practice plus optional steroids according to local best practice
Everolimus	basiliximab	Basiliximab plus everolimus-based immunosuppressive regimen following the reduction and cessation of initial CNI regimen plus optional steroids according to local best practice
Calcineurin Inhibitor (CNI)	basiliximab	Basiliximab plus CNI-based immunosuppressive regimen according to local best practice plus optional steroids according to local best practice

Primary Outcome Measures

Name	Time	Method
Calculated Glomerular Filtration Rate (cGFR)	Month 11	This outcome measure evaluated renal function by assessing the calculated GFR based on the Cockcroft-Gault formula.

Secondary Outcome Measures

Name	Time	Method
Patient and Graft Survival	Month 11	Patient survival was defined as the time from date of randomization to date of death from any cause. If a patient was not known to have died, patient survival was censored as the date of last contact. Graft survival was defined as the time from the date of randomization to the date of graft loss. If a patient was not known to suffer from a graft loss or died without graft loss, time to graft loss was censored with date of last contact or date of death, respectively. Patient and graft survival were analyzed using the Kaplan Meier method.
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death	Month 12 to Month 59 post-baseline	Patients with all (serious and non-serious) adverse events, serious adverse events and death were reported.
Incidence of Renal Deterioration	Baseline, Month 11	Renal deterioration was defined as a decrease by ≥25% in the cGFR compared to baseline and confirmed by one consecutive measurement. The analysis of this outcome measure was omitted because of missing relevance.
Incidence of Treated BPAR	Month 11	The incidence of treated BPAR was estimated using crude rate estimation (relative frequency).
Incidence of Efficacy Failure	Month 11	Efficacy failure was defined as the composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, death, lost to follow-up (from any reason), whichever occurred first. Incidence of efficacy failure was estimated using crude rate estimation (relative frequency).
Hepatitis C Virus (HCV) Replication in HCV-positive Patients	Baseline, Month 5	HCV ribonucleic acid (RNA) was measured by real time reverse transcriptase polymerase chain reaction (PCR; copies per mL).
Incidence of the Need for a Change in the Immunosuppressive Regimen	Month 11	The incidence of any changes in the immunosuppressive regimen other than allowed in the study protocol (for example, introduction of Mycophenolic acid (MPA) or sirolimus) was estimated using crude rate estimation (relative frequency).
Renal Function (cGFR)	Month 5	This outcome measure evaluated renal function by assessing the calculated GFR based on the Cockcroft-Gault formula.