- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01625377
A National Multi-center Randomized, Open Label Study to Evaluate Efficacy and Safety of Everolimus With EC-MPS Compared to Standard Treatment Combination Tacrolimus and EC-MPS in de Novo Liver Transplant Recipients (SIMCER)
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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-
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Besancon cedex, France, 25030
- Novartis Investigative Site
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Bordeaux Cedex, France, 33076
- Novartis Investigative Site
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Chambray les Tours, France, 37044
- Novartis Investigative Site
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Clichy, France, 92110
- Novartis Investigative Site
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Creteil, France, 94010
- Novartis Investigative Site
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Grenoble, France, 38043
- Novartis Investigative Site
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Lille Cedex, France, 59037
- Novartis Investigative Site
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Marseille, France, 13385
- Novartis Investigative Site
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Montpellier, France, 34295
- Novartis Investigative Site
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Nice, France, 06202
- Novartis Investigative Site
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Paris Cedex 13, France, 75651
- Novartis Investigative Site
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Rennes Cedex, France, 35033
- Novartis Investigative Site
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Toulouse Cedex 4, France, 31054
- Novartis Investigative Site
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Villejuif, France, 94800
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Key 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
Key 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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 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
|
Arm 1 : tacrolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to month 6 post-transplantation. Arm 2 : tacolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to 16 weeks post-transplantation at the latest.
Other Names:
Basiliximab was supplied to the participating centers as marketed, i.e. in packs containing one vial of 20-mg powder, and water for injection (WFI).
20 mg at D0 and D4
Other Names:
Dose of 1440 mg/day from transplantation to month 6 post- transplantation
Other Names:
Administration of oral corticosteroid therapy was at the discretion of the centers according to their usual practice
|
Experimental: 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). |
Arm 1 : tacrolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to month 6 post-transplantation. Arm 2 : tacolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to 16 weeks post-transplantation at the latest.
Other Names:
Basiliximab was supplied to the participating centers as marketed, i.e. in packs containing one vial of 20-mg powder, and water for injection (WFI).
20 mg at D0 and D4
Other Names:
Dose of 1440 mg/day from transplantation to month 6 post- transplantation
Other Names:
Administration of oral corticosteroid therapy was at the discretion of the centers according to their usual practice
Arm 1: no everolimus Arm 2: everolimus (C0 6-10 ng/ml) from randomization to month 6 post-transplantation
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
Baseline, Week 24
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients With Treatment Failures
Time Frame: At week 12 and week 24
|
Incidence of treatment failures, assessed with composite criterion including treated biopsy proven acute rejection (tBPAR) with a rejection activity index (RAI) according to Banff classification >3, graft loss or death at 6 months. Biopsy proven acute rejection (BPAR) was defined as a clinically suspected acute rejection confirmed by biopsy. The Banff Rejection Activity Index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation; bile duct inflammation damage; and portal inflammation; the scores are combined to an overall score (the RAI) ranging from 0 to 9. An overall score of 0-3 is considered indeterminate, score of 4-5 is mild acute, score of 6-7 is moderate acute , and score of 8-9 is severe acute. Only the episode with the highest total RAI score for each participant was counted. The graft was presumed to be lost on the day the patient was registered again on the waiting list, or the day he/she received a new graft. |
At week 12 and week 24
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Number of Patients With Treated or Not Treated Biopsy Proven Acute Rejection (BPAR)
Time Frame: at 12 week and 24 week
|
Biopsy proven acute rejection was defined as a clinically suspected acute rejection confirmed by biopsy.
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at 12 week and 24 week
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Number of Patients Reported With Different Categories of Severity of BPAR According to Banff Classification
Time Frame: at 12 week and 24 week
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Biopsy proven acute rejection was defined as a clinically suspected acute rejection confirmed by biopsy. The severity of BPAR was categorized as : Mild (Banff grade I, RAI = 4 and 5) Moderate (Banff grade II, RAI = 6 and 7) Severe (Banff grade III, RAI = 8 and 9) Banff Rejection Activity Index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation; bile duct inflammation damage; and portal inflammation; the scores are combined to an overall score (the RAI) ranging from 0 to 9. An overall score of 0-3 is considered indeterminate, score of 4-5 is mild acute, score of 6-7 is moderate acute , and score of 8-9 is severe acute. Only the episode with the highest total RAI score for each participant was counted. |
at 12 week and 24 week
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Number of Patients With Treated or Untreated BPAR With RAI Score Greater Than 3
Time Frame: At 24 weeks
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Biopsy proven acute rejection (BPAR) was defined as a clinically suspected acute rejection confirmed by biopsy. The Banff Rejection Activity Index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation; bile duct inflammation damage; and portal inflammation; the scores are combined to an overall score (the RAI) ranging from 0 to 9. An overall score of 0-3 is considered indeterminate, score of 4-5 is mild acute, score of 6-7 is moderate acute , and score of 8-9 is severe acute. Only the episode with the highest total RAI score for each participant was counted. The patients with treated or untreated BPAR having RAI score > 3 were reported in this end point. |
At 24 weeks
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Number of Patients With Death or Graft Loss
Time Frame: at week 24
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The graft was presumed to be lost on the day the patient was registered again on the waiting list, or the day he/she received a new graft.
|
at week 24
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Change From Baseline (Randomization) in Serum Creatinine
Time Frame: Baseline, Week 24
|
Change in serum creatinine concentrations from baseline (randomization) to week 24 post-randomization was one of the efficacy assessments of renal function. Baseline was Day 28 visit. |
Baseline, Week 24
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Change From Baseline (Randomization) in Urine Protein/Creatinine Ratio
Time Frame: Baseline, week 24
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Change in urine protein/creatinine ratio from baseline (randomization) to week 24 post-randomization was one of the efficacy assessments of renal function.
Baseline was Day 28 visit.
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Baseline, week 24
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Change From Baseline (Randomization) in Creatinine Clearance Estimated Using the Adjusted Cockcroft-Gault Formula
Time Frame: Baseline, Week 24
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Creatinine clearance by the Cockcroft-Gault formula is computed in mL/min/1.73m^2
from the creatinine clearance in mL/min by multiplying it by 1.73 and dividing it by the body surface area Baseline was Day 28 visit.
|
Baseline, Week 24
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Change From Baseline (Randomization) in Glomerular Filtration Rate Estimated by Abbreviated Modification of Diet in Renal Disease (MDRD) Formula
Time Frame: Baseline, Week 24
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Change in glomerular filtration rate was calculated using the MDRD abbreviated 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. |
Baseline, Week 24
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Change From Baseline (Randomization) in Glomerular Filtration Rate Estimated by CKD-EPI Formula
Time Frame: Baseline, Week 24
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GFR estimated by using the Chronic kidney disease- epidemiology (CKD-EPI) formula: eGFR (mL/min/1.73m^2) = 141 * min(C/K,1)^ α * max(C/K,1)^-1.209 * 0.993^A * 1.1018 (if male) * 1.159 (if black) where C = serum creatinine (in mg/dL) ; A = Age (in years); K = 0.7 for women and 0.9 for men; α = -0.329 for women and -0.411 for men. Baseline was Day 28 visit. |
Baseline, Week 24
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Number of Patients in Different Stages of Chronic Kidney Diseases According to the K/DOQI Classification System
Time Frame: At Week 24
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Kidney disease outcomes quality initiative (K/DOQI) classification is based on glomerular filtration rate (GFR), abbreviated MDRD formula (mL/min/1.73m^2) : Stage 1 : GFR >= 90; Stage 2 = GFR was between 60-89; Stage 3 = GFR was between 30-59 ; Stage 4 = GFR was between 15-29; Stage 5 = GFR was < 15 (or dialysis) |
At Week 24
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Number of Patients With Any Adverse Events, Serious Adverse Events, Death and Premature Discontinuation
Time Frame: Baseline to 24 weeks
|
Baseline was Day 28 visit.
This endpoint reports patients with total adverse events (any), serious adverse events, death and premature discontinuation.
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Baseline to 24 weeks
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Tacrolimus
- Mycophenolic Acid
- Everolimus
- Basiliximab
Other Study ID Numbers
- CRAD001HFR02
- 2012-000137-39 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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