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CompletedNCT03256864Updated Jun 5, 2020

Twice-daily Tacrolimus and Everolimus Convert to Once-daily Tacrolimus and Everolimus in Liver Transplant Recipient

A Phase 4 interventional study of Tacrolimus and Everolimus in Liver Transplantation, sponsored by Chang Gung Memorial Hospital. Completed at 1 site in Taiwan. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2020-06-05.

Sponsored by Chang Gung Memorial Hospital · Phase 4, Interventional, and Other

Phase
Phase 4
Study type
Interventional
Enrollment
10
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

It has been identified that nonadherence to immunosuppressant regimen may cause long-term graft failure and death in solid organ transplant recipients. Therefore, simplification of the immunosuppression regimen by reducing daily dosing frequency may improve long-term outcome. The investigators will examine pharmacokinetics and safety profiles of stable liver transplant recipients receiving twice-daily TAC with EVR (BID) regimen and then being converted to once-daily TAC with EVR (QD) regimen over a 6-month study period post-conversion.

Read the detailed description

Randomized trial of everolimus (EVR) with reduced tacrolimus (TAC) regimen after liver transplantation has shown similar incidence of composite efficacy failure rate to a standard tacrolimus regimen, but with superior renal function for up to three years. Recent studies have demonstrated comparable efficacy and safety profiles in liver transplant recipients receiving tacrolimus once-daily (QD) and tacrolimus twice-daily (BID) regimens. In kidney transplantation, once daily everolimus (QD) regimen has shown its safety and effectiveness. It has been identified that nonadherence to immunosuppressant regimen may cause long-term graft failure and death in solid organ transplant recipients. Therefore, simplification of the immunosuppression regimen (e.g. TAC with EVR) by reducing daily dosing frequency may improve long-term outcome. However, little is known about the effectiveness and safety of combined TAC and EVR once-daily (QD) regimen in liver transplant recipients. The investigator will examine pharmacokinetics and safety profiles of stable liver transplant recipients receiving twice-daily TAC with EVR (BID) regimen and then being converted to once-daily TAC with EVR (QD) regimen over a 6-month study period post-conversion.

02

Conditions studied

  • Liver Transplantation
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key inclusion criteria

Stable liver transplant recipients are eligible for inclusion in this study and have to fulfill all of the following criteria:

  1. Liver Transplant Recipients have received liver transplantations for at least 6+1 months prior to enrollment
  2. Liver Transplant Recipients have no acute rejection episodes within 3 months prior to the enrollment and are clinically stable
  3. Liver Transplant Recipients have been treated with twice-daily regimen of tacrolimus(TAC) plus everolimus(EVR) and TAC and EVR trough levels have stayed within targeted ranges for at least 6 weeks prior to enrollment
  4. Provide written informed consent prior to inclusion.
  5. Liver transplant recipients who are 18-65 years of age of a primary liver transplant
  6. Allograft functioning at an acceptable level as defined by the AST, ALT, Total Bilirubin levels ≤3 times ULN prior to enrollment.
  7. Abbreviated MDRD eGFR ≥ 30 mL/min/1.73m2. Key exclusion criteria

Patients fulfilling any of the following criteria are not eligible for inclusion in this study:

  1. Patients who are recipients of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant. Patients who have a combined liver-kidney transplant.
  2. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
  3. Existence of any surgical, medical or mental conditions, other than the current transplantation, which, in the opinion of the investigator, might interfere with the objectives of the study.
  4. Pregnant or nursing (lactating) women.
04

Study design

Phase
Phase 4
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
10 participants (actual)

Study arms

  • Experimental
    Tacrolimus and Everolimus BID

    TAC BID (C0 2.5-5 ng/mL) EVR BID (1.0 mg BID targeted to C0 3-8 ng/mL) Other Names: * Prograf * Advagraf * Zortress * Certican

    Drug: Tacrolimus and Everolimus

  • Experimental
    Tacrolimus and Everolimus QD

    TAC QD (C0 2.5-5 ng/mL) EVR QD (2.0 mg QD targeted to C0 3-8 ng/mL) Other Names: * Prograf * Advagraf * Zortress * Certican

    Drug: Tacrolimus and Everolimus

Interventions

  • DrugTacrolimus and Everolimus

    In the TAC and EVR BID arm, everolimus will be initiated at a dose of 1.0 mg BID within 24 h of randomization with the dose adjusted from day 5 onward to maintain trough (C0) concentration in the range 3-8 ng/mL. Tacrolimus will be initiated at a dose of 0.15 mg/kg BID and then taper to 0.10 mg/kg BID to maintain trough (C0) concentration in the range 2.5-5 ng/mL. In the TAC and EVR QD arm, everolimus will be initiated at a dose of 2.0 mg QD within 24 h of randomization with the dose adjusted from day 5 onward to maintain trough (C0) concentration in the range 3-8 ng/mL. Tacrolimus will be initiated at a dose of 0.1-0.2 mg/kg/day QD to maintain trough (C0) concentration in the range 2.5-5 ng/mL.

    Also known as: Prograf, Advagraf, Zortress, Certican

05

What researchers measure

Primary outcomes

  1. To evaluate pharmacokinetic profile of everolimus and tacrolimus in liver transplant recipients on AUC (area under the curve)

    Area under the plasma concentration versus time curve (AUC)

    Time frame: 6 month

06

Study locations

1 site
  • Chang Gung Memorial Hospital
    Taoyuan, Taiwan
07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03256864
Lead sponsor
Chang Gung Memorial Hospital
Responsible party
Wei-Chen Lee (Chief of transplanet center, Chang Gung Memorial Hospital) — Principal investigator
First posted
Aug 22, 2017
Start date
Jan 2016
Primary completion
Jun 30, 2019
Completion
May 30, 2020
Last update
Jun 5, 2020

Study contacts

WeiChen Lee, MD
principal investigator · Chang Gung Memorial Hospital

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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