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

NCT04258423 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: 1807596072
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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

Conditions

Kidney Failure

Outcome Measures

Primary Outcomes (3)

• Glomerular Filtration Rate in Patients Treated With Tacrolimus

  Glomerular Filtration Rate

  36 months post-transplant

• Glomerular Filtration Rate in Patients Treated With Everolimus

  Glomerular Filtration Rate

  36 months post-transplant

• Number of Patients Who Experience Transplant Rejection

  Biopsy

  36 months post-transplant

Study Arms (2)

Control Arm

ACTIVE COMPARATOR

Tacrolimus as maintenance immunosuppression

Drug: Tacrolimus

Study Arm

EXPERIMENTAL

Everolimus as maintenance immunosuppression

Drug: Everolimus

Interventions

Tacrolimus DRUG

Low dose Tacrolimus

Also known as: Prograf

Control Arm

Everolimus DRUG

Everolimus

Also known as: Zortress

Study Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Tacrolimus; Everolimus

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Sirolimus

Results Point of Contact

• Title: Dr. Chandrashekhar Kubal
• Organization: Indiana University

sakubal@iupui.edu

317-312-2601

Study Officials

• Chandrashekhar Kubal, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Tacrolimus as maintenance immunosuppression, then randomized to Everolimus plus Mycophenolate Mofetil, discontinuing Tacrolimus once Everolimus level within goal range OR randomized to continued maintenance with Tacrolimus plus Mycophenolate Mofetil.

Study Record Dates

• First Submitted: January 31, 2020
• First Posted: February 6, 2020
• Study Start: December 19, 2019
• Primary Completion: June 27, 2020
• Study Completion: June 27, 2020
• Last Updated: May 24, 2023
• Results First Posted: May 24, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)