Everolimus Monotherapy as Immunosuppression After Liver Transplant

NCT04063865 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: 1807401376
• Study Type: interventional
• Target: 14
• 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 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).

Conditions

Kidney Failure

Outcome Measures

Primary Outcomes (2)

• Long-Term Renal Function With Tacrolimus Monotherapy

  Glomerular Filtration Rate

  36 months post-transplant

• Long-Term Renal Function With Everolimus Monotherapy

  Glomerular Filtration Rate

  36 months post-transplant

Study Arms (2)

Control Arm

ACTIVE COMPARATOR

Tacrolimus as maintenance immunosuppression

Drug: Tacrolimus

Study Arm

EXPERIMENTAL

Everolimus monotherapy maintenance immunosuppression

Drug: Everolimus

Interventions

Tacrolimus DRUG

Tacrolimus (FK / Prograf) titrated to a goal trough of 6 - 8 ng/ml

Also known as: Prograf

Control Arm

Everolimus DRUG

Everolimus monotherapy - target trough levels 4 - 8 ng/ml as maintenance immunosuppression

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
• 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

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 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

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

IU Health University Hospital

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: 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: Princial Investigator

Model Details: Tacrolimus as maintenance immunosuppression

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: August 21, 2019
• Study Start: May 9, 2019
• Primary Completion: July 2, 2020
• Study Completion: July 2, 2020
• Last Updated: May 23, 2023
• Results First Posted: May 23, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)