Clinical trial NCT03500848: Sirolimus-based Immunosuppression Treatment Regimen for Liver Transplantation
Official title: Sirolimus-based Immunosuppression Treatment Regimen for Liver Transplantation: A Multicenter, Open-label, Randomized, Controlled Clinical Trial in Liver Transplant Recipients With Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Liver Transplantation
Keywords: Liver transplantation
Sirolimus
Tacrolimus
HCC recurrence free survival
Lead sponsor: Southern Medical University, China
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital, Sun Yat-Sen University
name: Nanfang Hospital, Southern Medical University
First posted: 2018-04-18
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: HCC recurrence free survival
timeFrame: Randomization to Month 36
Secondary outcomes:
measure: Overall survival
timeFrame: Randomization to Month 36
measure: Incidence of acute rejection
timeFrame: Randomization to Month 36
measure: Treatment failures defined as introduction of Tacrolimus to experimental group
timeFrame: Randomization to Month 36
measure: Graft survival
timeFrame: Randomization to Month 36
measure: Incidence of adverse events
timeFrame: Randomization to Month 36
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Guanzhou
country: China
facility: First Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
Study officials:
affiliation: Department of Heptobiliary Surgery II, Zhujiang Hospital, Southern Medical University, China
name: Kebo Zhong, M.D
role: PRINCIPAL_INVESTIGATOR
References: