Sirolimus-based Immunosuppression Treatment Regimen for Liver Transplantation

NCT ID: NCT03500848

Last Updated: 2018-04-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-01
• Study Completion Date: 2023-05-31

Brief Summary

This is a multicenter, open-label, randomized, controlled clinical trial, in order to compare sirolimus-based (tacrolimus-free) versus tacrolimus-based (sirolimus-free) immunosuppression regimen for Hepatocellular Carcinoma (HCC) patients after liver transplantation.

Detailed Description

This 5-year study consisted of a 2-year enrolment period and a 3-year follow-up period. Patients will be screened for eligibility prior to liver transplantation. Patients who have undergone successful liver transplantation will be initiated on a tacrolimus-based regimen that includes MMF and/or Steroids and enter the baseline period (between 3 and 7 days post-transplantation). At 30 (± 5) days post-transplantation, patients who meet additional randomization inclusion/exclusion criteria will be randomized into 2 groups of this study. In the first group, patients will be maintained on a tacrolimus-based (sirolimus-free) immunosuppression regimen. The second group will be treated with sirolimus-based (tacrolimus-free) immunosuppression regimen. For patients in both groups, mycophenolic acid prodrugs like mycophenolate mofetil (MMF) and steroids are initiated at the time of liver transplantation according to local practice. Steroids reduction is encouraged by 3 months post liver transplantation.

In the first year after randomization all patients will be followed up after month 1, 2, 3, 4, 5, 6, 8, 10 and 12. After that, patients are followed every 3 months. Tacrolimus and sirolimus trough levels in patients of both groups will be tested and adjusted if need be at each follow-up date to achieve the desired steady-state trough levels.

The primary endpoint is defined as HCC recurrence-free time interval between the date of liver transplantation and the date of HCC recurrence or death; patients who are alive and recurrence-free at the end of month 36 will be censored at the time of their last follow-up date. HCC recurrence can be determined during the entire follow-up period.

Conditions

Liver Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tacrolimus-based group

Tacrolimus-based immunosuppression regimen: Tacrolimus+MMF and/or steroids

Group Type: ACTIVE_COMPARATOR

Tacrolimus

Intervention Type: DRUG

Tacrolimus will be started between 3 and 7 days post-transplantation and continued after randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The tacrolimus trough level is measured twice a week for 1 month, followed by trough level once a month thereafter. Tacrolimus trough levels are targeted to be maintained at 8-15ng/ml until Month 6. After Month 6, the dose will be adjusted over time to maintain steady-state tacrolimus trough blood levels of approximately 5-10 ng/mL.

MMF and/or steroids

Intervention Type: DRUG

For patients in both groups, MMF and/or steroids are initiated at or prior to the time of liver transplantation according to local practice. Steroids reduction is encouraged by 3 months post liver transplantation.

Sirolimus-based group

Sirolimus-based immunosuppression regimen: Tacrolimus (Tacrolimus elimination 30 (± 5) days post LT)+Sirolimus+MMF and/or steroids

Group Type: EXPERIMENTAL

Tacrolimus (Tacrolimus elimination)

Intervention Type: DRUG

Tacrolimus will be started between 3 and 7 days post-transplantation at a dose of 1.0 mg twice a day (bid, 2 mg daily dose) for 30 (± 5) days and eliminated when randomization is done.

Sirolimus

Intervention Type: DRUG

Within 24 hours of randomization, sirolimus will be started at a dose of 2.0 mg once a day. The sirolimus trough level is measured twice a week for 1 month, followed by trough level once a month thereafter. The dose will be adjusted over time to maintain steady-state sirolimus trough blood levels of approximately 4-10 ng/mL.

MMF and/or steroids

Intervention Type: DRUG

For patients in both groups, MMF and/or steroids are initiated at or prior to the time of liver transplantation according to local practice. Steroids reduction is encouraged by 3 months post liver transplantation.

Interventions

Tacrolimus

Tacrolimus will be started between 3 and 7 days post-transplantation and continued after randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The tacrolimus trough level is measured twice a week for 1 month, followed by trough level once a month thereafter. Tacrolimus trough levels are targeted to be maintained at 8-15ng/ml until Month 6. After Month 6, the dose will be adjusted over time to maintain steady-state tacrolimus trough blood levels of approximately 5-10 ng/mL.

Intervention Type: DRUG

Tacrolimus (Tacrolimus elimination)

Tacrolimus will be started between 3 and 7 days post-transplantation at a dose of 1.0 mg twice a day (bid, 2 mg daily dose) for 30 (± 5) days and eliminated when randomization is done.

Intervention Type: DRUG

Sirolimus

Within 24 hours of randomization, sirolimus will be started at a dose of 2.0 mg once a day. The sirolimus trough level is measured twice a week for 1 month, followed by trough level once a month thereafter. The dose will be adjusted over time to maintain steady-state sirolimus trough blood levels of approximately 4-10 ng/mL.

Intervention Type: DRUG

MMF and/or steroids

For patients in both groups, MMF and/or steroids are initiated at or prior to the time of liver transplantation according to local practice. Steroids reduction is encouraged by 3 months post liver transplantation.

Intervention Type: DRUG

Other Intervention Names

FK-506; Fujimycin; Prograf; Protopic; Advagraf; FK-506; Fujimycin; Prograf; Protopic; Advagraf; Rapamune; Mycophenolate mofetil

Eligibility Criteria

Inclusion Criteria

• Recipients who are 18-65 years of age
• Histologically proven HCC before randomization
• Recipients who have been initiated on an immunosuppressive regimen that contains tacrolimus, 3-7 days post-transplantation
• Allograft is functioning at an acceptable level by the time of randomization as defined by protocol specific laboratory values
• Ability and willingness to provide written informed consent and adhere to study regimen

Exclusion Criteria

• Patients with non-HCC malignancies within the past 5 years
• Patients who are multiple-organ recipients
• Patients who are known HIV-positive patients
• Patients who have received mTOR inhibitors prior to day 30 after liver transplantation
• Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients
• 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 drug
• Patients with a psychologic, familial, sociologic or geographic condition potentially hampering compliance with the study protocol and follow-up schedule

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Southern Medical University, China

OTHER

Sponsor Role: lead

First Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: collaborator

Responsible Party

Chongyang Duan

Post-doctoral Fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kebo Zhong, M.D

Role: PRINCIPAL_INVESTIGATOR

Department of Heptobiliary Surgery II, Zhujiang Hospital, Southern Medical University, China

Locations

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, China

First Affiliated Hospital, Sun Yat-Sen University

Guanzhou, Guangdong, China

Countries

China

Central Contacts

Peihua Cao, Ph.D

Role: CONTACT

cphcc@smu.edu.cn

86-020-62783685

Facility Contacts

Peihua Cao, Ph.D

Role: primary

cphcc@smu.edu.cn

86-020-62783685

Chongyang Duan, M.D

Role: primary

donyduang@126.com

86-020-61649462

Other Identifiers

2017-GDEK-001

Identifier Type: -

Identifier Source: org_study_id