Skip to main content
Clinical Trials/NCT04258423
NCT04258423TerminatedPhase 3

Preservation of Renal Function After Liver Transplant for Patients With Pre-existing Chronic Kidney Disease or Peri-operative Acute Kidney Injury Using Everolimus Plus Mycophenolate Mofetil Immunosuppression Regimen

Indiana University1 site in 1 country4 target enrollmentStarted: December 19, 2019Last updated:
Conditions
Interventions
Drugs

Trial Snapshot

Phase
Phase 3
Status
Terminated
Enrollment
4
Locations
1
Primary Endpoint
Glomerular Filtration Rate in Patients Treated With Everolimus

Study Overview

Brief 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

Detailed Description

Following transplant, prior to the one month post transplant visit, subjects will be approached either in the transplant unit in the hospital or at the transplant clinic in the hospital for study participation. Following enrollment, subjects will be randomized at one month post transplant to reduced dose Tacrolimus plus Mycophenolate Mofetil immunosuppression (control group) or to Everolimus plus Mycophenolate Mofetil (study group) maintenance immunosuppression.

After liver transplant, all patients will receive the standard induction regimen and Tacrolimus monotherapy.

INDUCTION:

Rabbit anti-thymocyte globulin (rATG) 1.5 mg/kg of actual body weight rounded to nearest 25 mg and capped at 150 mg for up to three doses given IV on post-operative day (POD) 1, 3, and 5. Some patients may receive only one dose if considered too frail to need all three doses.

30 minutes prior to infusion, pre-medicate with the following: Daily steroid dose Acetaminophen (Tylenol®) 650 mg PO or per NG x 1 dose B - Lay Summary & Research Design Diphenhydramine (Benadryl®) 25 mg IV push x 1 dose

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Prevention
Masking
None

Eligibility Criteria

Ages
18 Years to — (Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

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

Arms & Interventions

Study Arm

Experimental

Everolimus as maintenance immunosuppression

Intervention: Everolimus (Drug)

Control Arm

Active Comparator

Tacrolimus as maintenance immunosuppression

Intervention: Tacrolimus (Drug)

Outcomes

Primary Outcomes

Glomerular Filtration Rate in Patients Treated With Everolimus

Time Frame: 36 months post-transplant

Glomerular Filtration Rate

Number of Patients Who Experience Transplant Rejection

Time Frame: 36 months post-transplant

Biopsy

Glomerular Filtration Rate in Patients Treated With Tacrolimus

Time Frame: 36 months post-transplant

Glomerular Filtration Rate

Secondary Outcomes

No secondary outcomes reported

Investigators

Sponsor Class
Other
Responsible Party
Principal Investigator
Principal Investigator

Chandrashekhar Kubal

Principal Investigator

Indiana University

Study Sites (1)

Loading locations...

Similar Trials

Everolimus Plus Mycophenolic Acid for... | Clinical Trial