A National, Multi-center, Randomized, Open Label Study to Evaluate the Efficacy and Safety of Everolimus Combined With Enteric-coated Mycophenolate Sodium Compared to the Standard Treatment Combining Tacrolimus and Enteric-coated Mycophenolate Sodium in de Novo Liver Transplant Recipients
Overview
- Phase
- Phase 3
- Intervention
- tacrolimus
- Conditions
- Liver Transplantation
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 188
- Locations
- 1
- Primary Endpoint
- Change From Baseline (Randomization) in Renal Function
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The aims of the study was to evaluate the safety and efficacy of early introduction one month post-transplantation of everolimus associated to EC-MPS with tacrolimus discontinuation in de novo liver transplant recipients and to evaluate if it leads to a better renal function 6 month post-transplantation compared to standard treatment associating tacrolimus and EC-MPS.
The renal function was estimated by glomerular filtration rate.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Man or woman aged 18 years or greater, recipient of a primary liver transplant from a deceased donor with whole or split liver
Exclusion Criteria
- •Patient recipient of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant
- •Recipient of a liver from a living donor or cadaveric non heart beating donor
- •ABO incompatible transplant graft
- •Transplantation following autoimmune liver hepatitis, primitive sclerosing cholangitis or primitive biliary cirrhosis
- •Estimated glomerular filtration rate ≤ 30ml/min at selection
- •History of malignancy within the 5 past years, other than non-metastatic basal or squamous cell carcinoma and hepatocellular carcinoma
- •Alpha-foeto-protein \> 1000 ng/ml (only in case of hepatocellular carcinoma)
Arms & Interventions
Tacrolimus
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : tacrolimus (C0 6-10 ng/ml) + mycophenolic acid 1440 mg/d ± oral corticosteroids
Intervention: tacrolimus
Tacrolimus
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : tacrolimus (C0 6-10 ng/ml) + mycophenolic acid 1440 mg/d ± oral corticosteroids
Intervention: Basiliximab
Tacrolimus
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : tacrolimus (C0 6-10 ng/ml) + mycophenolic acid 1440 mg/d ± oral corticosteroids
Intervention: Mycophenolic Acid
Tacrolimus
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : tacrolimus (C0 6-10 ng/ml) + mycophenolic acid 1440 mg/d ± oral corticosteroids
Intervention: Corticosteroids
Everolimus (RAD001)
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : everolimus (recommended starting dose of 2 mg/day, then adjusted to achieve the target 6 ≤ C0 ≤ 10 ng/mL, until W24) + mycophenolic acid 1440 mg/d ± oral corticosteroids. The dose of tacrolimus was reduced by 50% twice: at the introduction of everolimus and at week 8 post-transplantation. Tacrolimus had to be finally discontinued in week 12 post-transplantation (by week 16 at the latest).
Intervention: tacrolimus
Everolimus (RAD001)
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : everolimus (recommended starting dose of 2 mg/day, then adjusted to achieve the target 6 ≤ C0 ≤ 10 ng/mL, until W24) + mycophenolic acid 1440 mg/d ± oral corticosteroids. The dose of tacrolimus was reduced by 50% twice: at the introduction of everolimus and at week 8 post-transplantation. Tacrolimus had to be finally discontinued in week 12 post-transplantation (by week 16 at the latest).
Intervention: everolimus
Everolimus (RAD001)
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : everolimus (recommended starting dose of 2 mg/day, then adjusted to achieve the target 6 ≤ C0 ≤ 10 ng/mL, until W24) + mycophenolic acid 1440 mg/d ± oral corticosteroids. The dose of tacrolimus was reduced by 50% twice: at the introduction of everolimus and at week 8 post-transplantation. Tacrolimus had to be finally discontinued in week 12 post-transplantation (by week 16 at the latest).
Intervention: Basiliximab
Everolimus (RAD001)
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : everolimus (recommended starting dose of 2 mg/day, then adjusted to achieve the target 6 ≤ C0 ≤ 10 ng/mL, until W24) + mycophenolic acid 1440 mg/d ± oral corticosteroids. The dose of tacrolimus was reduced by 50% twice: at the introduction of everolimus and at week 8 post-transplantation. Tacrolimus had to be finally discontinued in week 12 post-transplantation (by week 16 at the latest).
Intervention: Mycophenolic Acid
Everolimus (RAD001)
From transplantation to randomization: Basiliximab (40mg) at Day 0 and Day 4 + tacrolimus (C0 6-10 ng/ml) from Day 3-Day 5 + mycophenolic acid 1440 mg/d ± oral corticosteroids. From randomization to month 6 : everolimus (recommended starting dose of 2 mg/day, then adjusted to achieve the target 6 ≤ C0 ≤ 10 ng/mL, until W24) + mycophenolic acid 1440 mg/d ± oral corticosteroids. The dose of tacrolimus was reduced by 50% twice: at the introduction of everolimus and at week 8 post-transplantation. Tacrolimus had to be finally discontinued in week 12 post-transplantation (by week 16 at the latest).
Intervention: Corticosteroids
Outcomes
Primary Outcomes
Change From Baseline (Randomization) in Renal Function
Time Frame: Baseline, Week 24
Change in renal function was measured by change in glomerular filtration rate (GFR). GFR calculated using the abbreviated modification of diet in renal disease (aMDRD) formula. GFR in mL/min/1.73m\^2 for men of non-black ethnicity: 186 \* \[C/88\]\^-1.154 \* \[A\]\^-0.023\*G\*R ; C = serum creatinine (in μmol/L); A = Age (in years). G = 0.742 when the patient is a women; Otherwise G=1 R= 1.21 when the patient was of black ethnicity; Otherwise R = 1 Baseline was Day 28 visit.
Secondary Outcomes
- Change From Baseline (Randomization) in Glomerular Filtration Rate Estimated by CKD-EPI Formula(Baseline, Week 24)
- Number of Patients in Different Stages of Chronic Kidney Diseases According to the K/DOQI Classification System(At Week 24)
- Number of Patients With Any Adverse Events, Serious Adverse Events, Death and Premature Discontinuation(Baseline to 24 weeks)
- Number of Patients With Treatment Failures(At week 12 and week 24)
- Number of Patients With Treated or Not Treated Biopsy Proven Acute Rejection (BPAR)(at 12 week and 24 week)
- Number of Patients Reported With Different Categories of Severity of BPAR According to Banff Classification(at 12 week and 24 week)
- Number of Patients With Treated or Untreated BPAR With RAI Score Greater Than 3(At 24 weeks)
- Number of Patients With Death or Graft Loss(at week 24)
- Change From Baseline (Randomization) in Serum Creatinine(Baseline, Week 24)
- Change From Baseline (Randomization) in Urine Protein/Creatinine Ratio(Baseline, week 24)
- Change From Baseline (Randomization) in Creatinine Clearance Estimated Using the Adjusted Cockcroft-Gault Formula(Baseline, Week 24)
- Change From Baseline (Randomization) in Glomerular Filtration Rate Estimated by Abbreviated Modification of Diet in Renal Disease (MDRD) Formula(Baseline, Week 24)