REnal Function in Liver Transplantation: Everolimus With Calcineurin Inhibitor (CNI)-Sparing sTrategy

Phase 3

Completed

Conditions: Liver Transplantation

Interventions: Drug: Everolimus
Drug: Tacrolimus

Registration Number: NCT02115113

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The purpose of this study was, starting from the Italian clinical practice in liver transplantation, to optimize the immunosuppressive therapy, considering specific patient characteristics as alcoholic cirrhosis, hepatitis C virus (HCV), hepatocellular carcinoma (HCC), and short/long-term implications. Then efficacy and safety of a calcineurin inhibitor (CNI)-withdrawal regimen was evaluated in comparison with a CNI-minimization regimen.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 78

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A (Tacrolimus Elimination Arm)	Everolimus	At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Tacrolimus was administered as per center practice. Thereafter, Everolimus doses were adjusted to achieve Everolimus C-0h blood trough levels between 3-8 ng/mL by week 1 after drug initiation until 5 months after transplant. At 5 months after transplant, Everolimus doses were adjusted to achieve C-0h blood trough level target ranges 6-10 ng/mL. Tacrolimus withdrawal was completed by 6 months after transplant.
Group A (Tacrolimus Elimination Arm)	Tacrolimus	At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Tacrolimus was administered as per center practice. Thereafter, Everolimus doses were adjusted to achieve Everolimus C-0h blood trough levels between 3-8 ng/mL by week 1 after drug initiation until 5 months after transplant. At 5 months after transplant, Everolimus doses were adjusted to achieve C-0h blood trough level target ranges 6-10 ng/mL. Tacrolimus withdrawal was completed by 6 months after transplant.
Group B (Tacrolimus Minimization Arm)	Tacrolimus	At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Tacrolimus was administered as per center practice. Thereafter, Everolimus doses were adjusted to achieve Everolimus C-0h blood trough levels between 3-8 ng/mL by week 1 after drug initiation until 5 months after transplant. At 5 months after transplant, Everolimus doses continued to be adjusted to achieve C-0h blood trough level target ranges 3-8 ng/mL and Tacorlimus doses were adjusted to achieve C-0h blood trough level target ranges 3-5 ng/mL.
Group B (Tacrolimus Minimization Arm)	Everolimus	At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Tacrolimus was administered as per center practice. Thereafter, Everolimus doses were adjusted to achieve Everolimus C-0h blood trough levels between 3-8 ng/mL by week 1 after drug initiation until 5 months after transplant. At 5 months after transplant, Everolimus doses continued to be adjusted to achieve C-0h blood trough level target ranges 3-8 ng/mL and Tacorlimus doses were adjusted to achieve C-0h blood trough level target ranges 3-5 ng/mL.

Primary Outcome Measures

Name	Time	Method
Renal Function Assessed by Estimated Glomerular Filtartion Rate (eGFR)	At 12 months post-transplant	Renal function was assessed by eGFR using the MDRD-4 formula at 12 months after transplant: eGFR = 186.3 \* (serum creatinine)-1.154 \* age-0.203 \* (0.742 for women) \* (1.21 if African American) where serum creatinine was in mg/dL and age in years.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Treated Biopsy Proven Acute Rejection (tBPAR) Acute Rejection (AR), Graft Loss (GL) or Death (D)	At 12 and 18 months post-transplant	Participants were assessed for tBPAR, AR, GL or death. For all suspected rejection episodes, regardless of initiation of anti-rejection treatment, a liver biopsy was to be performed preferably within 24 hours, latest within 48 hours whenever clinically possible. A treated biopsy proven acute rejection was considered an episode of acute rejection when demonstrated by local pathology reading with a rejection activity index of at least 3 or greater of acute rejection index and when treated with anti-rejection therapy. The allograft was considered lost on the day the subject was re-transplanted or died due to liver failure.
Change From Baseline (Randomization) in Serum Creatinine at 12 Months Post-transplant	baseline, 12 months post-transplant	Blood samples were collected to assess serum creatinine.