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Myfortic in High MELD Liver Transplantation

Primary Purpose

High Model for End-Stage Liver Disease (MELD) Score

Status

Withdrawn

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Everolimus, Myfortic and Tacrolimus

Myfortic and Tacrolimus

About this trial

This is an interventional treatment trial for High Model for End-Stage Liver Disease (MELD) Score

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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
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.

Sites / Locations

University of Colorado Denver

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Everolimus, Myfortic and Tacrolimus

Myfortic and Tacrolimus

Arm Description

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

Normal Care: Myfortic BID 360-720 mg Tacrolimus (5-12ng/mL)

Outcomes

Primary Outcome Measures

proven acute rejection

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01807767

First Posted

March 6, 2013

Last Updated

October 17, 2019

Sponsor

Medical College of Wisconsin

1. Study Identification

Unique Protocol Identification Number

NCT01807767

Brief Title

Myfortic in High MELD Liver Transplantation

Official Title

Prospective Evaluation of the Efficacy and Safety of Zortress (Everolimus)/Myfortic (Enteric Coated Mycophenolate Sodium) Conversion in High MELD Liver Transplantation

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Withdrawn

Why Stopped

funding was withdrawn

Study Start Date

March 2013 (undefined)

Primary Completion Date

July 2015 (Actual)

Study Completion Date

August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Medical College of Wisconsin

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

High Model for End-Stage Liver Disease (MELD) Score

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Everolimus, Myfortic and Tacrolimus

Arm Type

Experimental

Arm Description

Arm Title

Myfortic and Tacrolimus

Arm Type

Other

Arm Description

Normal Care: Myfortic BID 360-720 mg Tacrolimus (5-12ng/mL)

Intervention Type

Drug

Intervention Name(s)

Everolimus, Myfortic and Tacrolimus

Other Intervention Name(s)

Everolimus: Zortress, Certican, Afinitor, Myfortic: CellCept, Tacrolimus: FK-506, fujimycin, Prograf, Advagraf, Protopic

Intervention Description

Intervention Type

Drug

Intervention Name(s)

Myfortic and Tacrolimus

Other Intervention Name(s)

Myfortic: CellCept, Tacrolimus: FK-506, fujimycin, Prograf, Advagraf, Protopic

Intervention Description

Myfortic BID 360-720 mg Tacrolimus (5-12ng/mL)

Primary Outcome Measure Information:

Title

proven acute rejection

Description

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Zimmerman, MD

Organizational Affiliation

University of Colorado, Denver

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Colorado Denver

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

12. IPD Sharing Statement

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