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Examination of Immunosuppression Adjustment Impact on Kidney Function in Liver Transplant

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ClinicalTrials.gov Identifier: NCT04104438
Recruitment Status : Not yet recruiting
First Posted : September 26, 2019
Last Update Posted : October 1, 2019
Sponsor:
Information provided by (Responsible Party):
Fady M Kaldas, M.D., F.A.C.S., University of California, Los Angeles

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Asses Immunosuppression Modulation on Renal Recovery Post LT Drug: Basiliximab 20 MG Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: To assess the efficacy and safety of basiliximab, delayed dose tacrolimus plus mycophenolate mofetil, and SOC corticosteroids versus basiliximab, delayed dose tacrolimus plus mycophenolate mofetil, and SOC corticosteroids and addition of delayed everolimus/mycophenolate minimization at one month post OLT compared to standard triple immunosuppression (tacrolimus, mycophenolate mofetil and corticosteroids) for prevention of acute organ rejection in liver transplant recipients with a high risk of developing renal dysfunction following OLT or with concomitant renal dysfunction prior to OLT.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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).
Estimated Study Start Date : November 1, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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




Primary Outcome Measures :
  1. Renal Function [ Time Frame: 6 months ]
    Assessment of dialysis independence (patients no longer requiring dialysis post LT)


Other Outcome Measures:
  1. cumulative allograft rejection [ Time Frame: 6 months ]
    rejection rate based on pathologic criteria



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 78 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04104438


Contacts
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Contact: Fady M Kaldas, MD 310-825-5318 fkaldas@mednet.ucla.edu
Contact: Curtis D Holt, PharmD 310-206-4952 cholt@mednet.ucla.edu

Locations
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United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
Sponsors and Collaborators
Fady M Kaldas, M.D., F.A.C.S.
Investigators
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Principal Investigator: Fady M Kaldas, MD UCLA Dept Surgery
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Responsible Party: Fady M Kaldas, M.D., F.A.C.S., Clincal Professor of Surgery, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT04104438    
Other Study ID Numbers: Novartis18-000215
First Posted: September 26, 2019    Key Record Dates
Last Update Posted: October 1, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Everolimus
Basiliximab
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs