Liver TransplantationPhase 4NCT03256864
Twice-daily Tacrolimus and Everolimus Convert to Once-daily Tacrolimus and Everolimus in Liver Transplant Recipient
A Phase 4 study testing Tacrolimus and Everolimus in people with Liver Transplantation, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial 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. 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 and Everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteTaiwan
- Study dates
- Jan 2016to 30 May 2020
- Phase
- Phase 4
- 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
- Stable liver transplant recipients are eligible for inclusion in this study and have to fulfill all of the following criteria:
- 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
- Provide written informed consent prior to inclusion.
- Liver transplant recipients who are 18-65 years of age of a primary liver transplant
Show all 13Show fewer
- Allograft functioning at an acceptable level as defined by the AST, ALT, Total Bilirubin levels ≤3 times ULN prior to enrollment.
- 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:
- 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.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Liver Transplantation
- Being tested
- Tacrolimus and Everolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus and EverolimusDrug
Also called Prograf, Advagraf, Zortress, Certican
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Tacrolimus and Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 6 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2017
- Study startJan 2016
- Primary completion30 Jun 2019
- Study completion30 May 2020
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.
- More trials run by Chang Gung Memorial HospitalThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wei-Chen Lee, Chang Gung Memorial Hospital
- Investigators
- WeiChen Lee, MD, Principal investigator, Chang Gung Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03256864
- Sponsor's protocol ID
- CRAD001HTW02T
- Status last verified
- Jun 2020
- First submitted
- 1 Feb 2016
- Last updated
- 5 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03256864
- Acronym / sponsor ID
- CRAD001HTW02T
- Conditions
- Liver Transplantation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- Jan 2016
- Primary completion
- 30 Jun 2019 (actual)
- Study completion
- 30 May 2020 (actual)
- First posted
- 22 Aug 2017 (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.
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.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus and Everolimus BID | Experimental | Drug: Tacrolimus and EverolimusTAC 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 |
| Tacrolimus and Everolimus QD | Experimental | Drug: Tacrolimus and EverolimusTAC 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Stable liver transplant recipients are eligible for inclusion in this study and have to fulfill all of the following criteria:
- 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
- Provide written informed consent prior to inclusion.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Tacrolimus and EverolimusAlso: Prograf, Advagraf, Zortress, CerticanIn 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. | Drug | Tacrolimus and Everolimus BID, Tacrolimus and Everolimus QD |
Primary outcome
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2020.
- Individual participant dataSharing planned: Undecided
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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.
WeiChen Lee, MD principal investigator
Chang Gung Memorial Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tacrolimus and Everolimus in people with Liver Transplantation, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
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 13 inclusion and 0 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: finished, as of the sponsor's last update on 5 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate pharmacokinetic profile of everolimus and tacrolimus in liver transplant recipients on AUC (area under the curve) (time frame: 6 month). 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 5 Jun 2020.