Everolimus Monotherapy as Immunosuppression After Liver Transplant

• Status: Recruiting
• Trial end date: 2028-12-01
• 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 have near normal kidney function prior to liver transplantation. Other investigators have already shown a benefit in terms of renal function with introduction of Everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation, this benefit has been shown was maintained to 3 years in patients who continued Everolimus therapy with comparable efficacy and no late safety concerns. Investigators in this trial are proposing to advance this approach further by completely eliminating Tacrolimus from patients' immunosuppression protocol. The rationale for this approach is based on a unique induction immunosuppression protocol.

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. By completely eliminating Tacrolimus, investigators believe that there may be further benefit in terms of renal function. Additionally, Everolimus is known to induce tolerance in transplant recipients. Tolerant patients do not require immunosuppression to accept transplant organs.

The long-term efficacy and safety of Everolimus monotherapy as the maintenance immunosuppression in patients receiving rATG induction is unknown.

Primary Aim: Assess the effect of Everolimus monotherapy versus Tacrolimus monotherapy on long term renal function measured by Glomerular Filtration Rate (GFR).

• 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

• Normal baseline renal dysfunction (GFR > 60 mL/min)

• Rabbit anti-thymocyte globulin (rATG) induction (cumulative dose 1.5 - 5 mg/kg)

• Indication for transplant: ethanol, hepatitis C, or nonalcoholic steatohepatitis or any combination of these

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 months prior to transplantation

• Insurance company unwilling to pay for the cost of the everolimus or patient does not qualify for the Novartis Patient Assistance Program.

• Pregnant women

• Unable to provide informed consent