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

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ClinicalTrials.gov Identifier: NCT03256864
Recruitment Status : Recruiting
First Posted : August 22, 2017
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Wei-Chen Lee, Chang Gung Memorial Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Liver Transplantation Drug: Tacrolimus and Everolimus Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Six-month, Prospective, Single-center, Pilot Study Determining the Pharmacokinetics and Effectiveness of Twice-daily Tacolimus and Everolimus Regimen Convert to Once-daily Tacrolimus and Everolimus Regimen in Liver Transplant Patients
Study Start Date : January 2016
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : April 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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

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.

Other Names:
  • Prograf
  • Advagraf
  • Zortress
  • Certican

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

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.

Other Names:
  • Prograf
  • Advagraf
  • Zortress
  • Certican




Primary Outcome Measures :
  1. To evaluate pharmacokinetic profile of everolimus and tacrolimus in liver transplant recipients on AUC (area under the curve) [ Time Frame: 6 month ]
    Area under the plasma concentration versus time curve (AUC)



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT03256864


Contacts
Contact: WeiChen Lee, MD 8863281200 weichen@cgmh.org.tw

Locations
Taiwan
Chang Gung Memorial Hospital Recruiting
Taoyuan, Taiwan
Contact: Wei-Chen Lee    03-3281200 ext 3631      
Sponsors and Collaborators
Chang Gung Memorial Hospital
Investigators
Principal Investigator: WeiChen Lee, MD Chang Gung Memorial Hospital

Responsible Party: Wei-Chen Lee, Chief of transplanet center, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT03256864     History of Changes
Other Study ID Numbers: CRAD001HTW02T
First Posted: August 22, 2017    Key Record Dates
Last Update Posted: July 20, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Tacrolimus
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents