Examination of Immunosuppression Adjustment Impact on Kidney Function in Liver Transplant

A Study in Adults on Pre LT Dialysis With Basiliximab, Delayed Tacrolimus (TAC), Mycophenolate (MMF), Steroids (Grp 1) vs. Basiliximab, Delayed TAC, MMF, Steroids, With Everolimus 30d Post LT(Grp 2), vs. TAC, MMF, Steroids (Grp 3).

This is a study to help understand how well new combinations of immunosuppressive medications (medications that weaken your immune system to prevent your body from rejecting the transplanted liver) work compared to standard immunosuppressive medications after your liver transplant. Also the study will assess how safe the new combination of immunosuppressive medicines are and if there are any changes in how your kidneys work after taking these medicines.

Study Overview

• Status: Recruiting
• Conditions: Asses Immunosuppression Modulation on Renal Recovery Post LT
• Intervention / Treatment: Drug: Basiliximab 20 MG

Detailed Description

A single center, open label, randomized, prospective, pilot study of induction and maintenance immunosuppression in adult subjects >18 years undergoing orthotopic liver transplantation (OLT) with Basiliximab, delayed dose tacrolimus plus mycophenolate mofetil and standard of care (SOC) corticosteroids (Group 1) versus basiliximab, delayed dose tacrolimus plus mycophenolate mofetil, SOC corticosteroids, with addition of delayed maintenance Everolimus at one month post OLT with subsequent mycophenolate mofetil minimization (Group 2) versus standard dose tacrolimus plus mycophenolate mofetil plus SOC corticosteroids (Group 3; control) with concomitant renal dysfunction prior to OLT.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Fady M Kaldas, MD; Phone Number: 310-267-9608; Email: fkaldas@mednet.ucla.edu
• Study Contact Backup: Name: June Ramsay; Phone Number: 310-267-9608; Email: JRamsay@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Medical Center
      • Contact: Fady M Kaldas, MD; Phone Number: 310-267-9608; Email: fkaldas@mednet.ucla.edu
      • Contact: June Ramsay; Phone Number: 310-267-9608; Email: JRamsay@mednet.ucla.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 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:

  1. A signed informed consent prior to patient participation in the study and before any assessment is performed.
  2. Patients who are able to take oral medication.
  3. 18 years old
  4. Undergoing first OLT
  5. Dialysis for 45 days or less at time of transplant
  6. Able and willing to conform to requirements of the study

  7. Able and willing to provide informed consent

     Exclusion Criteria:

  1. < 18 years old
  2. Autoimmune liver disease, Primary Sclerosing Cholangitis, Primary Biliary Cirrhosis
  3. Dialysis greater than 45 days
  4. Receiving ATG, IVIG therapy, or sirolimus/everolimus around time of transplant or sirolimus/everolimus after transplant
  5. Unable to take oral medications
  6. Participating in another clinical research study involving the evaluation of another investigational drug or device
  7. Documented allergy to basiliximab, TAC, MMF or any macrolide antibiotic.
  8. Presence of thrombosis of any major hepatic arteries
  9. Complex/high risk arterial reconstruction at any time (graft vessel patency by Doppler ultrasound confirmed and documented).
  10. Patients who are recipients of multiple solid organ transplants, (e.g., multivisceral or combined liver-kidney transplants), or have previously received an organ or tissue transplanted, or who received an ABO incompatible transplant.
  11. Patients who have severe hypercholesterolemia (>215 mg/dL; >5.5 mmol/L) or hypertriglyceridemia (>265 mg/dL; >3.0 mmol/L) at Baseline.
  12. Patients who have severe thrombocytopenia or neutropenia (platelet count >20 and MLCs>1000)
  13. Patients who have any surgical or medical condition, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and excretion of study drugs
  14. Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients.
  15. Patients with clinically significant systemic infection
  16. Pregnant or nursing (lactating) female patients, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive βHCG laboratory test (>9 mIU/mL) at Baseline.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Basiliximab with Delayed TAC; Basiliximab; Dose #1: 20mg IV within 2 hours of transplant; Dose #2: 20mg IV Post-operative day #4 Tacrolimus (with basiliximab induction) o Beginning day #5 post-transplant or when SCr < 1.8 mg/dl (subjects off dialysis) to six months: 0.03-0.1mg/kg q12h PO to maintain whole blood trough concentration of 4-6ng/mL Mycophenolate mofetil o 1000 mg po bid Corticosteroids (SOC): Per UCLA protocol Post-operative taper: Post-op day 1- methylprednisolone 50mg IVP Q6H; Post-op day 2- methylprednisolone 40mg IVP Q6H; Post-op day 3- methylprednisolone 30mg IVP Q6H; Post-op day 4- methylprednisolone 20mg IVP Q6H; Post-op day 5- methylprednisolone 20mg IVP Q12H; Post-op day 6- methylprednisolone 10mg IVP Q12H until taking PO, then change to: prednisone 20mg PO QAM	Drug: Basiliximab 20 MG; Basiliximab induction followed by tacrolimus, corticosteroids and mycophenolic acid with a switch to everolimus by post operative day 30; Other Names: Everolimus
Active Comparator: Basliximab, Delayed TAC with Everolimus; Basiliximab Tacrolimus (with basiliximab induction) o Beginning day #5 post-transplant or when SCr < 1.8 mg/dl (subjects off dialysis) to POD 30: 0.03-0.1mg/kg q12h PO to maintain whole blood trough concentration of 4-6ng/mL Mycophenolate mofetil o 1000 mg po bid up to POD 30: reduce mycophenolate mofetil following achievement of steady state everolimus (POD 35) as clinically indicated Corticosteroids (SOC): Per UCLA protocol Everolimus (delayed) o Add by POD 30: 1 mg po bid and adjusted to maintain whole blood trough concentrations of 3-8 ng/ml.	Drug: Basiliximab 20 MG; Basiliximab induction followed by tacrolimus, corticosteroids and mycophenolic acid with a switch to everolimus by post operative day 30; Other Names: Everolimus
No Intervention: Control: standard TAC with steroids and MMF; Tacrolimus (without basiliximab induction); Beginning day #1 post-transplant to six months: 0.03-0.1mg/kg q12h po to maintain whole blood trough concentration of 5-12ng/mL; Six months to one year: maintain whole blood trough concentration of 5-10ng/mL Mycophenolate mofetil o 1000 mg po bid Corticosteroids (SOC): Per UCLA protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal Function	Assessment of dialysis independence (patients no longer requiring dialysis post LT)	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
cumulative allograft rejection	rejection rate based on pathologic criteria	6 months

Collaborators and Investigators

• Sponsor: Fady M Kaldas, M.D., F.A.C.S.
• Investigators: Principal Investigator: Fady M Kaldas, MD, UCLA Dept Surgery

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: May 30, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 26, 2019

Study Record Updates

• Last Update Posted (Actual): July 8, 2022
• Last Update Submitted That Met QC Criteria: July 6, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus; Basiliximab
• Other Study ID Numbers: Novartis18-000215

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No