High Model for End-Stage Liver Disease (MELD) ScoreNCT01807767
Myfortic in High MELD Liver Transplantation
A study testing Everolimus, Myfortic and Tacrolimus and Myfortic and Tacrolimus in people with High Model for End-Stage Liver Disease (MELD) Score, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
The objective of the study is to determine the efficacy and safety of Everolimus conversion in liver transplantation. Most large US liver centers transplant patients with high Model for End-Stage Liver Disease (MELD) scores. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- High Model for End-Stage Liver Disease (MELD) Score
- What is being tested?
- Everolimus, Myfortic and Tacrolimus and Myfortic and Tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to Aug 2015
- Phase
- Interventional
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must give written informed consent before any assessment is performed.
- MELD ≥ 25.
- Recipients who are 18-70 years of age of a primary or secondary liver transplant from a deceased donor.
- Allograft is functioning at an acceptable level by the time of randomization as defined by the Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Total Bilirubin levels ≤3 times Upper Limit of Normal (ULN), and Alkaline Phosphatase (AlkP) levels ≤ 5 times ULN.
- Ability and willingness to provide written informed consent and adhere to study regimen.
- Patients who are able to take oral medication at time of randomization. Glomerular Filtration Rate (GFR) ≥ 30 ml/min.
Who cannot join
- Patients receiving 3rd transplants
- Fulminant hepatic failure
- Living donor transplants
- Donation after Cardiac Death (DCD) donors or split grafts
- Active infection or hemodynamic instability at the time of transplant
- Renal replacement therapy for clearance within 7 days prior to randomization
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- Presence of thrombosis via Doppler ultrasound of the major hepatic arteries, major hepatic veins, portal vein and inferior vena cava.
- An episode of acute rejection that required antibody therapy or more than one steroid sensitive episode of acute rejection prior to randomization. This includes patients who have not completed steroid treatment for acute rejection within 7 days prior to randomization.
- Spot urine protein/creatinine ratio > 1g/24h at time of randomization
- Combined liver/kidney transplant
- Patients who have severe hypercholesterolemia (>350 mg/dL) or Patients with platelet count < 50,000 at time of randomization
- Patients with an Absolute neutrophil count (ANC) of < 1,000 or White Blood Count (WBC) of <2,000 at time of randomization
- Patients with hemoglobin <6g/dL
- Patients who are unable to take oral medication at time of randomization
- Patients with clinically significant systemic infection requiring active use of IV antibiotics, anti-virals, or anti-fungals
- Patients who are in a critical care setting at the time of randomization requiring life support measures such as mechanical ventilation, dialysis, requirement of vasopressor agents
- Known intolerance to tacrolimus or everolimus or Myfortic.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver
Aurora, Colorado, 80045
About this study
Official title: Prospective Evaluation of the Efficacy and Safety of Zortress (Everolimus)/Myfortic (Enteric Coated Mycophenolate Sodium) Conversion in High MELD Liver Transplantation
The objective of the study is to determine the efficacy and safety of Everolimus conversion in liver transplantation. Most large US liver centers transplant patients with high Model for End-Stage Liver Disease (MELD) scores. However, many of the sponsored liver transplant trials in the US do not include patients with high MELD scores making it difficult to extrapolate these trial data to the patients cared for at larger liver transplant centers. The greatest potential benefit of mammalian target of rapamycin (mTOR) inhibitors is the avoidance of the side-effects of calcineurin-inhibitors, namely, renal insufficiency, diabetes and hypertension. Therefore, this protocol is designed to study the efficacy and safety of everolimus and Myfortic in liver transplant patients with high MELD scores at two large centers with a vast experience in the administration of mTOR inhibitors.
- Being tested
- Everolimus, Myfortic and Tacrolimus, Myfortic and Tacrolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus, Myfortic and TacrolimusDrug
Also called Everolimus: Zortress, Certican, Afinitor, Myfortic: CellCept, Tacrolimus: FK-506, fujimycin, Prograf, Advagraf, Protopic
Tacrolimus discontinued (within 8 weeks of initiation of everolimus conversion).
Everolimus 1mg BID started (targeted trough 6-12ng/mL). Patients must have an everolimus concentration between 6-12ng/mL before tacrolimus is discontinued.
Myfortic 360-720 mg BID
Myfortic and TacrolimusDrug
Also called Myfortic: CellCept, Tacrolimus: FK-506, fujimycin, Prograf, Advagraf, Protopic
Myfortic BID 360-720 mg Tacrolimus (5-12ng/mL)
| Study group | Role | What they receive |
|---|---|---|
| Everolimus, Myfortic and Tacrolimus | Experimental | Tacrolimus discontinued (within 8 weeks of initiation of everolimus conversion).
Everolimus 1mg BID started (targeted trough 6-12ng/mL). Patients must have an everolimus concentration between 6-12ng/mL before tacrolimus is discontinued.
Myfortic 360-720 mg BID Receives: Drug: Everolimus, Myfortic and Tacrolimus |
| Myfortic and Tacrolimus | Other | Normal Care: Myfortic BID 360-720 mg Tacrolimus (5-12ng/mL) Receives: Drug: Myfortic and Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
proven acute rejection
- To evaluate the use of a calcineurin-free immunosuppressive regimen utilizing concentration-controlled everolimus and mycophenolic acid (Myfortic) (Arm #12), in order to compare rates of the composite efficacy endpoint (biopsy proven-acute rejection, graft loss, and death) to the rates in the CNI-containing control arm (Arm #21) at 12 months post conversion to everolimus.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2013 (estimated)
- Study startMar 2013
- Primary completionJul 2015
- Study completionAug 2015
Why it stopped: funding was withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Model for End-Stage Liver Disease (MELD) ScoreStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Zimmerman, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01807767
- Sponsor's protocol ID
- 12-0457
- Other IDs
- CRAD001HUS63T
- Status last verified
- Oct 2019
- First submitted
- 6 Mar 2013
- Last updated
- 21 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Evaluation of the Efficacy and Safety of Zortress (Everolimus)/Myfortic (Enteric Coated Mycophenolate Sodium) Conversion in High MELD Liver Transplantation
- ClinicalTrials.gov ID
- NCT01807767
- Acronym / sponsor ID
- 12-0457
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: funding was withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- Jul 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 8 Mar 2013 (estimated)
- 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.
The objective of the study is to determine the efficacy and safety of Everolimus conversion in liver transplantation. Most large US liver centers transplant patients with high Model for End-Stage Liver Disease (MELD) scores. However, many of the sponsored liver transplant trials in the US do not include patients with high MELD scores making it difficult to extrapolate these trial data to the patients cared for at larger liver transplant centers. The greatest potential benefit of mammalian target of rapamycin (mTOR) inhibitors is the avoidance of the side-effects of calcineurin-inhibitors, namely, renal insufficiency, diabetes and hypertension. Therefore, this protocol is designed to study the efficacy and safety of everolimus and Myfortic in liver transplant patients with high MELD scores at two large centers with a vast experience in the administration of mTOR inhibitors.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus, Myfortic and Tacrolimus | Experimental | Drug: Everolimus, Myfortic and TacrolimusTacrolimus discontinued (within 8 weeks of initiation of everolimus conversion). Everolimus 1mg BID started (targeted trough 6-12ng/mL). Patients must have an everolimus concentration between 6-12ng/mL before tacrolimus is discontinued. Myfortic 360-720 mg BID |
| Myfortic and Tacrolimus | Other | Drug: Myfortic and TacrolimusNormal Care: Myfortic BID 360-720 mg Tacrolimus (5-12ng/mL) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must give written informed consent before any assessment is performed.
- MELD ≥ 25.
- Recipients who are 18-70 years of age of a primary or secondary liver transplant from a deceased donor.
- Allograft is functioning at an acceptable level by the time of randomization as defined by the Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Total Bilirubin levels ≤3 times Upper Limit of Normal (ULN), and Alkaline Phosphatase (AlkP) levels ≤ 5 times ULN.
- Ability and willingness to provide written informed consent and adhere to study regimen.
Key exclusion criteria (17 listed)
- Patients receiving 3rd transplants
- Fulminant hepatic failure
- Living donor transplants
- Donation after Cardiac Death (DCD) donors or split grafts
- Active infection or hemodynamic instability at the time of transplant
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 |
|---|---|---|
| Everolimus, Myfortic and TacrolimusAlso: Everolimus: Zortress, Certican, Afinitor, Myfortic: CellCept, Tacrolimus: FK-506, fujimycin, Prograf, Advagraf, ProtopicTacrolimus discontinued (within 8 weeks of initiation of everolimus conversion). Everolimus 1mg BID started (targeted trough 6-12ng/mL). Patients must have an everolimus concentration between 6-12ng/mL before tacrolimus is discontinued. Myfortic 360-720 mg BID | Drug | Everolimus, Myfortic and Tacrolimus |
| Myfortic and TacrolimusAlso: Myfortic: CellCept, Tacrolimus: FK-506, fujimycin, Prograf, Advagraf, ProtopicMyfortic BID 360-720 mg Tacrolimus (5-12ng/mL) | Drug | Myfortic and Tacrolimus |
Primary outcome
proven acute rejection
Time frame: 12 months
1. To evaluate the use of a calcineurin-free immunosuppressive regimen utilizing concentration-controlled everolimus and mycophenolic acid (Myfortic) (Arm #12), in order to compare rates of the composite efficacy endpoint (biopsy proven-acute rejection, graft loss, and death) to the rates in the CNI-containing control arm (Arm #21) at 12 months post conversion to everolimus.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2019.
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.
Michael Zimmerman, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Everolimus, Myfortic and Tacrolimus and Myfortic and Tacrolimus in people with High Model for End-Stage Liver Disease (MELD) Score, run by Medical College of Wisconsin at 1 site in United States.
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 6 inclusion and 17 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: withdrawn, as of the sponsor's last update on 21 Oct 2019. 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 United States. 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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
proven acute rejection (time frame: 12 months). 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 21 Oct 2019.