Clinical trial NCT02115113: REnal Function in Liver Transplantation: Everolimus With Calcineurin Inhibitor (CNI)-Sparing sTrategy
Official title: Multicenter, Prospective, Open-label, Controlled, Randomized, Parallel Groups Study to Evaluate the Renal Function of Adult Liver Transplant Recipients Treated With Two Everolimus-based Immunosuppressive Regimens (Tacrolimus Withdrawal vs. Minimization) Until 12 Months Post-transplant, With a 6-months Follow-up
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Liver Transplantation
Keywords: Liver transplantation, everolimus, CNI-minimization, CNI-elimination, renal function
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-04-15
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion criteria at Baseline:

* Male and female liver transplant recipients who are ≥ 18 years of age, treated with a tacrolimus-based immunosuppressive regimen, who have received an induction therapy or i.v. steroids as per local clinical practice.
* Recipients of a full-size or technically modified liver allograft will be eligible at 4 weeks (± 7 days) after liver transplantation.
* Allograft is functioning at an acceptable level by the time of Baseline as defined by the AST, ALT, total bilirubin levels ≤ 3 times ULN and INR \< 1.5 times ULN.
* Abbreviated MDRD-4 eGFR ≥ 30 mL/min/1.73m2. Serum creatinine results obtained within 5 days prior to Baseline are acceptable.

Inclusion criteria at Randomization:

* Effective tacrolimus minimization, confirmed by stable blood trough levels in the two months prior to randomization, i.e. verification of last two tacrolimus blood trough level ≤ 5 ng/mL in the two months prior to randomization. Investigators should make adjustments in tacrolimus dosing to continue to target trough levels ≤ 5 ng/mL prior to randomization.
* Abbreviated MDRD-4 eGFR ≥ 30 mL/min/1.73m2. Serum creatinine results obtained within 5 days prior to Visit 5 are acceptable.

Exclusion criteria at Baseline:

* Patients who are recipients of multiple solid organ transplants, (e.g., multivisceral or combined liver-kidney transplants), or have previously received an organ or tissue transplanted, or who received an AB0 incompatible transplant.
* Patients who experienced more than one episode of treated biopsy proven acute rejection (BANFF ≥ 3 or RAI ≥ 7) or one steroid-resistant acute rejection.
* Patients who require renal replacement therapy.
* Patients with a confirmed spot urine protein/creatinine ratio that indicates ≥1.0 g/24 hrs of proteinuria.
* History of malignancy of any organ system within the past 5 years whether or not there is evidence of local recurrence or metastases, other than non-metastatic basal or squamous cell carcinoma of the skin or HCC.

Exclusion criteria at Randomization:

* Patients who experienced more than two episodes of treated biopsy proven acute rejection (BANFF ≥ 3 or RAI ≥ 7) since transplantation or one steroid-resistant acute rejection during the run-in period.
* Patients with a confirmed spot urine protein/creatinine ratio that indicates ≥ 3.0 g/24 hrs of proteinuria.

Primary outcomes:
measure: Renal Function Assessed by Estimated Glomerular Filtartion Rate (eGFR)
timeFrame: At 12 months post-transplant
Secondary outcomes:
measure: Percentage of Participants With Treated Biopsy Proven Acute Rejection (tBPAR) Acute Rejection (AR), Graft Loss (GL) or Death (D)
timeFrame: At 12 and 18 months post-transplant
measure: Change From Baseline (Randomization) in Serum Creatinine at 12 Months Post-transplant
timeFrame: baseline, 12 months post-transplant
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Bari
country: Italy
facility: Novartis Investigative Site
state: BA
city: Bergamo
country: Italy
facility: Novartis Investigative Site
state: BG
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Udine
country: Italy
facility: Novartis Investigative Site
state: UD
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Napoli
country: Italy
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: