Safety and Efficacy of Basiliximab, Delayed Dose Tacrolimus Plus ECMPA (Enteric Coated Mycophenolic Acid) Following Liver Transplantation

September 14, 2022 updated by: Fady M Kaldas, M.D., F.A.C.S., University of California, Los Angeles

Safety and Efficacy of Basiliximab, Delayed Dose Tacrolimus Plus ECMPA, Versus Standard Dose Tacrolimus, ECMPA Plus Corticosteroids in Patients Undergoing Liver Transplant

This is an investigator initiated study at the University of California, Los Angeles (UCLA) funded by Novartis looking at using a combination of immunosuppressive drugs in liver transplant patients that are at risk of developing kidney problems. Kidney problems following liver transplants is the most problematic issue facing liver transplant patients today.

This study will generate information in this area of high unmet medical need utilizing basiliximab and Myfortic and using a reduced dose of tacrolimus, one of the current standard of care medications, after kidney function has normalized.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Since basiliximab works on the same receptor system as tacrolimus and has not been shown to cause significant adverse effects, such as nephrotoxicity or the cytokine release syndrome, the investigators are proposing induction therapy with basiliximab in liver transplant patients with concomitant preoperative renal dysfunction. This will combat acute rejection and allow the delay of tacrolimus therapy until post-operative day #7. The delay in tacrolimus therapy should allow renal function to improve and reduce the chance of continued renal dysfunction. Also, the addition of basiliximab to the immunosuppressive regimen should allow for a reduction in tacrolimus dose (normal tacrolimus concentrations at UCLA are 7-10ng/mL. Our goal will be 3-5ng/mL) in the immediate post-transplant period thereby reducing the chance of acute and long-term efficacy-limiting adverse effects associated with the tacrolimus while maintaining adequate immunosuppression to reduce acute rejection episodes. This would be the most convincing prospective randomized study utilizing basiliximab as a renal sparing agent in liver transplantation.

Objectives Primary objectives

• To evaluate renal recovery/ function following OLT in patients undergoing orthotopic liver transplant at 6 and 12 months post-transplant.

Secondary objectives (comparing the two treatment arms)

  • To determine the tolerability and adverse event profile during the first year post-transplant.
  • To determine incidence and severity acute rejection episodes
  • To determine the incidence of death and/or graft failure within the first year post-transplant

Study design The study is a single center prospective randomized trial wherein the investigators will have two groups. Patients will be screened and eligible patients will be enrolled pre-transplant. Patients will then be randomized at time of transplant to either the control or treatment arm. Post transplant laboratory data (chemistry, tacrolimus level and liver function tests) will be collected on a daily basis. For the duration of the patients' hospital stay (average 2-3 weeks). This will provide the early data set for early post operative results. Patients will subsequently be followed on a weekly outpatient basis upon discharge as per protocol. During these visits, laboratory data (chemistry, tacrolimus level and liver function tests) are also collected and will provide the continued flow of data for our follow up analysis. Any evidence of rejection will prompt treatment with rescue therapy and if necessary disenrollment from the study.

Study Type

Interventional

Enrollment (Actual)

59

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Ronald Reagan UCLA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients eligible for inclusion in this study have to fulfill all of the following criteria:

  • >18 years old
  • Undergoing first or second OLT
  • MELD (model for end-stage liver disease) score >25
  • Serum creatinine > 1.5 or ongoing hemodialysis for less than 4 weeks at the time of transplant
  • Able and agreeable to conform to requirements of the study
  • Patients or proxy must give written informed consent before any assessment is performed.

Exclusion Criteria:

  • <18 years old
  • Serum creatinine <1.5
  • MELD Score < 25
  • Ongoing hemodialysis for 4 or more weeks (those patients become eligible for renal transplants at that point per UCLA practice).
  • Receiving OKT3 (Muromonab-CD3), ATG (Antithymocyte Globulin), or IVIG (Intravenous Immunoglobulin Therapy) therapy around time of transplant
  • Participating in another clinical research study involving the evaluation of another investigational drug or device
  • Prior documented allergy to any of the study medications
  • Active Fungal infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Basiliximab
Tacrolimus with Basiliximab induction
Drug: Basiliximab
Peri-operative 40 mg IV dose within 4 hours of OLT Postoperative 20mg IV dose Day 4
Other Names:
  • Simulect
Drug: Tacrolimus
Day #7 post-transplant or when serum creatinine (SCr) < 1.8 mg/dl 6 months to 1 year: 0.03-0.1 mg.kg q12h po to maintain whole blood trough concentration of 3-5ng/mL
Other Names:
  • Prograf
Drug: Tacrolimus
Day #1 post-transplant to 6 months: 0.03-0.1mg/kg q12h po to maintain whole blood trough concentration of 7-10 ng/mL + 6 months to 1 year: maintain whole blood trough concentration of 5-8ng/mL
Other Names:
  • Prograf
Drug: Mycophenolic Acid
Enteric coated mycophenolic acid 360-720 mg po bid
Other Names:
  • Myfortic
  • Mycophenolate sodium
Active Comparator: Tacrolimus Group
Tacrolimus (without basiliximab induction); standard of care group
Drug: Tacrolimus
Day #7 post-transplant or when serum creatinine (SCr) < 1.8 mg/dl 6 months to 1 year: 0.03-0.1 mg.kg q12h po to maintain whole blood trough concentration of 3-5ng/mL
Other Names:
  • Prograf
Drug: Tacrolimus
Day #1 post-transplant to 6 months: 0.03-0.1mg/kg q12h po to maintain whole blood trough concentration of 7-10 ng/mL + 6 months to 1 year: maintain whole blood trough concentration of 5-8ng/mL
Other Names:
  • Prograf
Drug: Mycophenolic Acid
Enteric coated mycophenolic acid 360-720 mg po bid
Other Names:
  • Myfortic
  • Mycophenolate sodium

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Renal Recovery/ Function
Time Frame: 12 months post-transplant
Number of participants who experienced dialysis independence or improvement based upon kidney function labs as a measure of renal recovery/ function following OLT in patients after undergoing orthotopic liver transplant
12 months post-transplant

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Participants Experiencing Adverse Event Attributable to Study Drug
Time Frame: 12 months post liver transplantation
12 months post liver transplantation
Participants Experiencing Acute Rejection Episode
Time Frame: 12 months post liver transplant
12 months post liver transplant
Survival
Time Frame: 12 months post liver transplant
Participants at risk minus incidence of death within the first year post-transplant
12 months post liver transplant
Participants Experiencing Graft Failure
Time Frame: 12 months post transplant
12 months post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Los Angeles

Collaborators

Novartis

Investigators

  • Principal Investigator: Fady M Kaldas, MD, UCLA Department of Surgery

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

February 24, 2014

First Submitted That Met QC Criteria

April 23, 2014

First Posted (Estimate)

April 25, 2014

Study Record Updates

Last Update Posted (Actual)

September 29, 2022

Last Update Submitted That Met QC Criteria

September 14, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCLA: CCHI621AUS17T

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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