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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
276
Start dose of everolimus was 1.5 mg in the morning followed by 1.5 mg in the evening. After one week, the dose was adjusted to achieve trough levels between 5-12 ng/mL. Once trough levels were above 5ng/mL, the CNI dose was reduced to 70%. At week 8 post-baseline (latest at week 16 post baseline), CNI was completely discontinued. For patients receiving Ciclosporin A (CiA) as CNI, the everolimus dosage was adjusted to achieve a trough level of 8-12 ng/mL, prior to discontinuation of CiA. After discontinuation of CNI, everolimus was maintained at a trough level of 5-12 ng/mL.
All patients who met the eligibility criteria were treated with 2 doses of basiliximab on Day 0 (transplantation) and Day 4.
Patients who met the screening eligibility received CNI-based immunosuppressive therapy for 1 month. Then at week 4 (or week 8 at maximum), patients randomized to the CNI arm continued on CNI-based immunosuppressive therapy.
Novartis Investigative Site
Innsbruck, Austria
Novartis Investigative Site
Vienna, Austria
Novartis Investigative Site
Berlin, Germany, Germany
Calculated Glomerular Filtration Rate (cGFR)
This outcome measure evaluated renal function by assessing the calculated GFR based on the Cockcroft-Gault formula.
Time frame: Month 11
Incidence of Efficacy Failure
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).
Time frame: Month 11
Incidence of the Need for a Change in the Immunosuppressive Regimen
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).
Time frame: Month 11
Incidence of Renal Deterioration
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.
Time frame: Baseline, Month 11
Renal Function (cGFR)
This outcome measure evaluated renal function by assessing the calculated GFR based on the Cockcroft-Gault formula.
Time frame: Month 5
Incidence of Treated BPAR
The incidence of treated BPAR was estimated using crude rate estimation (relative frequency).
Time frame: Month 11
Patient and Graft Survival
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Novartis Investigative Site
Essen, Germany
Novartis Investigative Site
Frankfurt, Germany
Novartis Investigative Site
Hamburg, Germany
Novartis Investigative Site
Hanover, Germany
Novartis Investigative Site
Heidelberg, Germany
Novartis Investigative Site
Jena, Germany
Novartis Investigative Site
Münster, Germany
...and 6 more locations
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.
Time frame: Month 11
Hepatitis C Virus (HCV) Replication in HCV-positive Patients
HCV ribonucleic acid (RNA) was measured by real time reverse transcriptase polymerase chain reaction (PCR; copies per mL).
Time frame: Baseline, Month 5
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death
Patients with all (serious and non-serious) adverse events, serious adverse events and death were reported.
Time frame: From randomization to Month 11
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death
Patients with all (serious and non-serious) adverse events, serious adverse events and death were reported.
Time frame: Month 12 to Month 59 post-baseline