Clinical trial NCT04104438: Examination of Immunosuppression Adjustment Impact on Kidney Function in Liver Transplant
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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asses Immunosuppression Modulation on Renal Recovery Post LT
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2019-09-26
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 78
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility 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:

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  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.

Primary outcomes:
measure: Renal Function
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
measure: cumulative allograft rejection
timeFrame: 6 months
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
Study officials:
affiliation: UCLA Dept Surgery
name: Fady M Kaldas, MD
role: PRINCIPAL_INVESTIGATOR
References: