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

NCT03256864 | Completed Phase 4

• 1 other identifier: CRAD001HTW02T
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Transplantation

Outcome Measures

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)

  6 month

Study Arms (2)

Tacrolimus and Everolimus BID

EXPERIMENTAL

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

Tacrolimus and Everolimus QD

EXPERIMENTAL

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

Tacrolimus and Everolimus DRUG

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

Tacrolimus and Everolimus BID; Tacrolimus and Everolimus QD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Liver Transplant Recipients have received liver transplantations for at least 6+1 months prior to enrollment
• Liver Transplant Recipients have no acute rejection episodes within 3 months prior to the enrollment and are clinically stable
• 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
• Liver transplant recipients who are 18-65 years of age of a primary liver transplant
• Allograft functioning at an acceptable level as defined by the AST, ALT, Total Bilirubin levels ≤3 times ULN prior to enrollment.

You may not qualify if:

• 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.
• 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.
• 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.
• Pregnant or nursing (lactating) women.

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Chang Gung Memorial Hospital

Taoyuan District, Taiwan

Location

MeSH Terms

Interventions

Tacrolimus; Everolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Sirolimus

Study Officials

• WeiChen Lee, MD

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of transplanet center

Study Record Dates

• First Submitted: February 1, 2016
• First Posted: August 22, 2017
• Study Start: January 1, 2016
• Primary Completion: June 30, 2019
• Study Completion: May 30, 2020
• Last Updated: June 5, 2020

Record last verified: 2020-06

Locations

TW (1)