Efficacy of Everolimus in Combination With Tacrolimus in Liver Transplant Recipients

Study Overview
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Brief Summary
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This trial evaluated the efficacy and safety of Everolimus in combination with tacrolimus versus a standard immunosuppressive regimen concerning kidney function in liver transplant recipients.

Official Title
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A 12-month, Multi-center, Open-label, Randomized, Controlled Study to Evaluate Efficacy/Safety and Evolution of Renal Function of Everolimus in Co-exposure With Tacrolimus in de Novo Liver Transplant Recipients

Conditions
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Liver Transplantation

Intervention / Treatment
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* Drug: Everolimus
* Drug: Tacrolimus
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female recipients of a full-size liver allograft, aged 18 to 65 years. Exclusion criteria: Patients with thrombocytopenia (platelets <50,000/mm³), with an absolute neutrophil count of <1,000/mm³ or leucopenia (leucocytes <2000/mm³), with anemia with Hb < 6g/dl at time of randomization Patients with uncontrolled hypercholesterolemia (>350mg/dL; >9mmol/L) or hypertriglyceridemia (>750 mg/dL; >8.5 mmol/L) at time of randomization 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EVR/TAC<br>Tacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: < 5 ng/mL) | Drug: Everolimus<br>* tablet containing 0.25mg, 0.5mg, 0.75mg or 1.0mg<br>* Other names: RAD001 / Certican;Drug: Tacrolimus<br>* capsule containing 0.5, 1.0, or 5.0mg<br>* Other names: Tacrolimus Hexal;Drug: Corticosteroids<br>* For patients in all groups, corticosteroids were initiated at or prior to the time of transplantation according to local practice. Corticosteroids may have been used for the duration of the study according to the investigator's discretion, but may not have been eliminated sooner than 6 months post-transplantation.<br>|
| Active Comparator: TAC<br>Tacrolimus (C0-h: 6-10 ng/ml) | Drug: Tacrolimus<br>* capsule containing 0.5, 1.0, or 5.0mg<br>* Other names: Tacrolimus Hexal;Drug: Corticosteroids<br>* For patients in all groups, corticosteroids were initiated at or prior to the time of transplantation according to local practice. Corticosteroids may have been used for the duration of the study according to the investigator's discretion, but may not have been eliminated sooner than 6 months post-transplantation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated Glomerular Filtration Rate (GFR) | The estmated GFR was calculated using MDRD-4 formula (Modification of Diet in Renal Disease Study Group). | month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated GFR - PP Set | This was a sensitivity analysis for the primary outcome measure based on the per-protocol set of patients. | month 12 | 
| Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death | Percentage of Participants with Treated Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death at Month 12 | 12 months | 
| Number of Participants With HCV | Number of Participants with HCV (hepatitis C virus) assessed as treatment emergent adverse events of special interest | 12 months | 
| Incidence of HCV Related Fibrosis | Incidence of hepatitis C virus (HCV) related fibrosis assessed as treatment emergent adverse events of special interest | 12 months | 
| Incidence of de Novo HCC Malignancies | Incidence of de novo Hepatocellular Carcinoma (HCC) malignancies assessed as treatment emergent adverse events of special interest | 12 months | 
| Incidence and Severity of CMV Viral Infections. | Incidence and severity of cytomegalovirus (CMV) viral infections assessed as treatment emergent adverse events of special interest. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver transplantation, Everolimus, Tacrolimus, Renal function