Liver TransplantationPhase 2/3NCT03500848
Sirolimus-based Immunosuppression Treatment Regimen for Liver Transplantation
A Phase 2/3 study testing Tacrolimus, Tacrolimus (Tacrolimus elimination) and Sirolimus in people with Liver Transplantation, run by Southern Medical University, China at 3 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Liver Transplantation
- What is being tested?
- Tacrolimus, Tacrolimus (Tacrolimus elimination) and Sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 3 sitesChina
- Study dates
- 1 May 2018to 31 May 2023
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
China3 sites
Zhujiang Hospital of Southern Medical University
Guangzhou, Guangdong, 510282
Peihua Cao, Ph.D, 86-020-62783685, cphcc@smu.edu.cn
Kebo Zhong, M.D
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, 510515
Chongyang Duan, M.D, 86-020-61649462, donyduang@126.com
Dinghua Yang, M.D
First Affiliated Hospital, Sun Yat-Sen University
Guanzhou, Guangdong, 510080
About this study
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
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.
Read the 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
- Being tested
- Tacrolimus, Tacrolimus (Tacrolimus elimination), Sirolimus, MMF and/or steroids
- Keywords
- Liver transplantation, Sirolimus, Tacrolimus, HCC recurrence free survival
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TacrolimusDrug
Also called FK-506, Fujimycin, Prograf, Protopic
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.
Tacrolimus (Tacrolimus elimination)Drug
Also called FK-506, Fujimycin, Prograf, Protopic
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.
SirolimusDrug
Also called Rapamune
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 steroidsDrug
Also called Mycophenolate mofetil
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.
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus-based group | Active comparator | Tacrolimus-based immunosuppression regimen: Tacrolimus+MMF and/or steroids Receives: Drug: Tacrolimus; Drug: MMF and/or steroids |
| Sirolimus-based group | Experimental | Sirolimus-based immunosuppression regimen: Tacrolimus (Tacrolimus elimination 30 (± 5) days post LT)+Sirolimus+MMF and/or steroids Receives: Drug: Tacrolimus (Tacrolimus elimination); Drug: Sirolimus; Drug: MMF and/or steroids |
What is being measured
The primary outcome is the main question the study is designed to answer.
HCC recurrence free survival
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.
Measured: Randomization to Month 36
Secondary outcomes (5)
Overall survival
Overall survival was defined as the time from date of randomization to date of death from any cause. If a patient was not known to have died, patient overall survival was censored as the date of last contact.
Measured: Randomization to Month 36
Incidence of acute rejection
Incidence of acute rejection will be assessed in both groups.
Measured: Randomization to Month 36
Treatment failures defined as introduction of Tacrolimus to experimental group
Treatment failures defined as introduction of Tacrolimus to experimental group
Measured: Randomization to Month 36
Graft survival
Graft survival was defined as the time from the date of randomization to the date of graft loss. If a patient was not known to suffer from a graft loss or died without graft loss, time to graft loss was censored with date of last contact or date of death, respectively.
Measured: Randomization to Month 36
Incidence of adverse events
Evaluation of common post Liver Transplantation Adverse Events: wound healing, bone marrow depression, hyperlipidemia, proteinuria, diabetes mellitus, diagnosed hypertension, infections.
Measured: Randomization to Month 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2018
- Study start1 May 2018 (estimated)
- Primary completion31 May 2023 (estimated)
- Study completion31 May 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Southern Medical University, China
- Sponsor type
- University, hospital or other
- Collaborators
- First Affiliated Hospital, Sun Yat-Sen University, Nanfang Hospital, Southern Medical University
- Responsible party
- Principal investigator, Chongyang Duan, Southern Medical University, China
- Investigators
- Kebo Zhong, M.D, Principal investigator, Department of Heptobiliary Surgery II, Zhujiang Hospital, Southern Medical University, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03500848
- Sponsor's protocol ID
- 2017-GDEK-001
- Status last verified
- Apr 2018
- First submitted
- 29 Mar 2018
- Last updated
- 18 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03500848
- Acronym / sponsor ID
- 2017-GDEK-001
- Conditions
- Liver Transplantation
- Keywords
- Liver transplantation, Sirolimus, Tacrolimus, HCC recurrence free survival
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Southern Medical University, ChinaUniversity, hospital or other
- Collaborators
- First Affiliated Hospital, Sun Yat-Sen University, Nanfang Hospital, Southern Medical University
- Study start
- 1 May 2018 (estimated)
- Primary completion
- 31 May 2023 (estimated)
- Study completion
- 31 May 2023 (estimated)
- First posted
- 18 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus-based group | Active comparator | Drug: Tacrolimus, Drug: MMF and/or steroidsTacrolimus-based immunosuppression regimen: Tacrolimus+MMF and/or steroids |
| Sirolimus-based group | Experimental | Drug: Tacrolimus (Tacrolimus elimination), Drug: Sirolimus, Drug: MMF and/or steroidsSirolimus-based immunosuppression regimen: Tacrolimus (Tacrolimus elimination 30 (± 5) days post LT)+Sirolimus+MMF and/or steroids |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TacrolimusAlso: FK-506, Fujimycin, Prograf, ProtopicTacrolimus 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. | Drug | Tacrolimus-based group |
| Tacrolimus (Tacrolimus elimination)Also: FK-506, Fujimycin, Prograf, ProtopicTacrolimus 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. | Drug | Sirolimus-based group |
| SirolimusAlso: RapamuneWithin 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. | Drug | Sirolimus-based group |
| MMF and/or steroidsAlso: Mycophenolate mofetilFor 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. | Drug | Sirolimus-based group, Tacrolimus-based group |
Primary outcome
HCC recurrence free survival
Time frame: Randomization to Month 36
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.
5 secondary outcomes
Overall survival
Time frame: Randomization to Month 36
Incidence of acute rejection
Time frame: Randomization to Month 36
Treatment failures defined as introduction of Tacrolimus to experimental group
Time frame: Randomization to Month 36
Graft survival
Time frame: Randomization to Month 36
Incidence of adverse events
Time frame: Randomization to Month 36
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2018.
- Individual participant dataSharing planned: Undecided
Related trials for Liver Transplantation
Not yet recruitingObservational study
Prevalence and Development of Liver Dysfunction in Hematopoietic Stem Cell Transplant
Hematopoietic Stem Cell Transplant
Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
Not yet recruiting
New Biomarkers for Organ Viability Assessment During Hypothermic Machine Perfusion in Liver Transplantation: the Role of Extemporaneous Histological Examination.
Liver Transplantation (LT), Early Allograft Dysfunction
RecruitingPhase 2
Expanding Liver Transplant Immunosuppression Minimization Via Everolimus
Liver Transplant
RecruitingObservational study
Long-term Follow-up (LTFU) Study of Participants in Any iECURE Protocol Using an Investigational Product (IP)
Ornithine Transcarbamylase Deficiency, Ornithine Transcarbamylase Deficiency Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kebo Zhong, M.D principal investigator
Department of Heptobiliary Surgery II, Zhujiang Hospital, Southern Medical University, China
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Tacrolimus, Tacrolimus (Tacrolimus elimination) and Sirolimus in people with Liver Transplantation, run by Southern Medical University, China at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Peihua Cao, Ph.D (86-020-62783685, cphcc@smu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HCC recurrence free survival (time frame: Randomization to Month 36). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2018.