Examination of Immunosuppression Adjustment Impact on Kidney Function in Liver Transplant

Fady M Kaldas, M.D., F.A.C.S.

Status and phase: Completed; Phase 4

Conditions: Asses Immunosuppression Modulation on Renal Recovery Post LT

Treatments: Drug: Basiliximab 20 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT04104438

Novartis18-000215

Details and patient eligibility

About

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.

Full 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.

Enrollment: 71 patients

Sex: All

Ages: 18 to 78 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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71 participants in 3 patient groups

basiliximab with Delayed TAC

Active Comparator group

Description:

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

Treatment:

Drug: Basiliximab 20 MG

basiliximab, Delayed TAC with Everolimus

Active Comparator group

Description:

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.

Treatment:

Drug: Basiliximab 20 MG

Control: standard TAC with steroids and MMF

No Intervention group

Description:

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