Efficacy and Safety of Everolimus in Liver Transplant Recipients of Living Donor Liver Transplants

Phase 3

Completed

Conditions: Liver Transplantation

Interventions: Drug: Everolimus + reduced tacrolimus
Drug: Standard tacrolimus

Registration Number: NCT01888432

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The purpose of this trial was to demonstrate the efficacy and safety of everolimus in combination with reduced tacrolimus, compared to tacrolimus control, in living donor liver transplant recipients.

Detailed Description: This study was 24 month, multicenter study in 280 living donor liver transplant patients from Asia, Europe and Canada. The study has an long term extension in Japan and approximately 28 patients were to be included to evaluate the long-term efficacy and safety of concentration-controlled everolimus regimen plus reduced tacrolimus compared to standard tacrolimus in recipients of living donor liver transplants in Japan who participated in the CRAD001H2307 study.

Data reported here are the CRAD001H2307 core study results and its extension (CRAD001H2307E1).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 285

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Everolimus + reduced tacrolimus	Everolimus + reduced tacrolimus	Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus	Standard tacrolimus	Standard tacrolimus ± corticosteroids

Primary Outcome Measures

Name	Time	Method
Number of Participants With Composite Efficacy Failure of Treated Biopsy Proven Acute Rejection, Graft Loss or Death in Everolimus With Reduced Tacrolimus Group Compared to Standard Tacrolimus	12 months post transplantation	Rate of composite efficacy failure of treated biopsy proven acute rejection (tBPAR ≥ RAI score 3), graft loss (GL) or death (D) in everolimus with reduced tacrolimus group compared to standard tacrolimus at 12 months

Secondary Outcome Measures

Name	Time	Method
Compare Incidence of Notable Safety Events (SAEs, Infections and Serious Infections Leading to Premature Discontinuation)	Month 24	Notable events include death, Serious AE/infection,, and AE/infection leading to discontinuation of study medication.
Composite Efficacy Failure of Treated Biopsy in Everolimus With Reduced Tacrolimus Group Compared to Standard Tacrolimus in Patients From Japan Only	randomization, 36 months post transplantion	Rate of composite efficacy failure of treated biopsy in everolimus with reduced tacrolimus group compared to standard tacrolimus from randomization in core study up to 36 months in the extension study. Composite endpoint = treated BPAR, graft loss or death. AR = Acute rejection; tAR = treated AR; BPR = biopsy proven rejection; BPAR = biopsy proven acute rejection; tBPAR = treated BPAR
Renal Function by Estimated Glomerular Filtration Rate (All Extension Patients)	randomization, at 36 months post transplantation	Renal function (change in estimated glomerular filtration rate (eGFR)) from randomization to Month 36 post transplantation with everolimus (EVR) in combination with reduced tacrolimus (rTAC) compared to standard exposure tacrolimus (TAC) in living donor liver transplant recipients in Japan
Renal Function by Estimated Glomerular Filtration Rate (eGFR) From Randomization	From randomization to month 12	Renal function (change in estimated glomerular filtration rate (eGFR)) from randomization to Month 12 post transplantation with everolimus (EVR) in combination with reduced tacrolimus (rTAC) compared to standard exposure tacrolimus (TAC) in living donor liver transplant recipients.
Compare Renal Function Over Time Assessed by the Change by eGFR, Post-randomization	From randomziation to month 24	Change in renal function from randomization to month 24 assessed by the change in estimated GFR (MDRD-4). Rate of change of renal function.
Compare Incidence of tBPAR	Month 12 and Month 24 post transplantation	Compare between the treatment group EVR with rTAC vs standard TAC: Incidence of tBPAR
Number of Subjects Experiencing Adverse Events/Infections by SOC	Month 24
Compare Incidence of AR	Month 12 and Month 24 post transplantation	Compare between the treatment group EVR with rTAC vs standard TAC: incidence of acute rejection (AR)
Number of Participants With Composite of tBPAR, Graft Loss, and Death	Month 24 post transplantation	Compare between the treatment group EVR with rTAC vs standard TAC: incidence of a composite of tBPAR, graft loss, death
Compare Incidence of BPAR	Month 12 and Month 24 post transplantation	Compare between the treatment group EVR with rTAC vs standard TAC: incidence of a composite of biopsy proven acute rejection (BPAR)
Compare Incidence of Graft Loss	Month 12 and Month 24 post transplantation	Compare between the treatment group EVR with rTAC vs standard TAC: incidence of graft loss
Compare Incidence of a Composite of Death or Graft Loss	Month 12 and Month 24 post transplantation	Compare between the treatment group EVR with rTAC vs standard TAC: Incidence of a composite of death or graft loss
Compare Incidence of Death	Month 12 and Month 24 post transplantation	Compare between the treatment group EVR with rTAC vs standard TAC: incidence of death
Compare Incidence of tAR	Month 12 and Month 24 post transplantation	Compare between the treatment group EVR with rTAC vs standard TAC: incidence of treated acute rejection (tAR).
Number of Participants With Time to Recurrence of HCC in Subjects With a Diagnosis of HCC at the Time of Liver Transplantation	Month 12 and Month 24	Patients transplanted for HCC or with HCC diagnosed at time of transplantation were monitored for HCC recurrence according to local practice. For example routine laboratory monitoring/tests, tumor markers, hepatic ultrasound, computed tomography scans (CAT, CT) or MRI (especially Fe-MRI) on a regular basis per local practice.