Everolimus Plus Mycophenolic Acid for Kidney Preservation in Liver Transplant Recipients With Impaired Kidney Function

• Status: Recruiting
• Trial end date: 2029-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Tacrolimus is the standard immunosuppressive drug used to prevent organ rejection post liver transplant. One side effect of Tacrolimus is nephrotoxicity. Everolimus does not have the nephrotoxicity side effects of Tacrolimus. Replacement of Tacrolimus by Everolimus may have a reduced incidence of renal dysfunction in liver transplant patients who already have chronic kidney disease or peri-operative acute kidney injury. Liver transplant patients receive potent induction immunosuppression in the form of rabbit anti thymocyte globulin. Investigators believe that in conjunction with this induction regimen, patients can be maintained on Everolimus monotherapy without the risk of rejection. Additionally, Everolimus is known to induce tolerance in transplant recipients. Tolerant patients do not require immunosuppression to accept transplant organs. Tacrolimus is a widely used in liver transplant recipients for immunosuppression, however it is associated with nephrotoxicity. Everolimus, on the other hand lacks nephrotoxicity. Whether replacement of tacrolimus by Everolimus preserves kidney function in patients with pre-existing chronic kidney disease or acute kidney injury is not well established. Also, the efficacy and safety of reduced-dose Everolimus with or without Mycophenolate Mofetil in prevention of rejection is unknown.

Primary Aim Assess the effect of Everolimus with or without Mycophenolate Mofetil versus Tacrolimus plus Mycophenolate Mofetil therapy on renal function measured by Glomerular Filtration Rate (GFR). Secondary Aims

Compare the efficacy of Everolimus plus Mycophenolate Mofetil versus Tacrolimus plus Mycophenolate Mofetil therapy as measured by the following:

• Biopsy-confirmed acute rejection

• Hyperlipidemia

• Proteinuria

• % regulatory T-cells in circulation

• NODAT [New Onset Diabetes mellitus After Transplant], hypertension and malignancy

• Tolerance measured by gene profiling at year 1, 2 and 3

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Indiana University
• Treatments: Everolimus; Sirolimus; Tacrolimus

Criteria

Inclusion Criteria:

• Liver transplant recipients ≥ 18 years old

• Baseline renal dysfunction (GFR ≤ 60 mL/min)

• Rabbit anti-thymocyte globulin (rATG) induction (cumulative dose 3 - 5 mg/kg)

• Indication for transplant: ethanol, hepatitis C, or nonalcoholic steatohepatitis

Exclusion Criteria:

• Increased risk of rejection: autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, positive crossmatch, retransplantation

• Incompletely healed incision or other wound healing issues at time of randomization

• Multiple or previous organ transplantation

• Severe, uncontrolled hypercholesterolemia (> 9mmol/L) or hypertriglyceridemia (>8.5 mmol/L) in the 6 mo prior to transplantation

• Insurance company unwilling to pay for the cost of the everolimus

• Pregnant women

• Unable to provide informed consent