Myfortic in High MELD Liver Transplantation

NCT ID: NCT01807767

Last Updated: 2019-10-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2015-08-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Everolimus, Myfortic and Tacrolimus

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

Group Type: EXPERIMENTAL

Everolimus, Myfortic and Tacrolimus

Intervention Type: DRUG

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 Tacrolimus

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

Group Type: OTHER

Myfortic and Tacrolimus

Intervention Type: DRUG

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

Interventions

Everolimus, Myfortic and Tacrolimus

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

Intervention Type: DRUG

Myfortic and Tacrolimus

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

Intervention Type: DRUG

Other Intervention Names

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

Eligibility Criteria

Inclusion Criteria

Patients must give written informed consent before any assessment is performed.

1. MELD ≥ 25.

2. Recipients who are 18-70 years of age of a primary or secondary liver transplant from a deceased donor.

3. 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.

4. Ability and willingness to provide written informed consent and adhere to study regimen.

5. Patients who are able to take oral medication at time of randomization. Glomerular Filtration Rate (GFR) ≥ 30 ml/min.

Exclusion Criteria

1. Patients receiving 3rd transplants

2. Fulminant hepatic failure

3. Living donor transplants

4. Donation after Cardiac Death (DCD) donors or split grafts

5. Active infection or hemodynamic instability at the time of transplant

6. Renal replacement therapy for clearance within 7 days prior to randomization

7. Presence of thrombosis via Doppler ultrasound of the major hepatic arteries, major hepatic veins, portal vein and inferior vena cava.

8. 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.

9. Spot urine protein/creatinine ratio > 1g/24h at time of randomization

10. Combined liver/kidney transplant

11. Patients who have severe hypercholesterolemia (>350 mg/dL) or Patients with platelet count < 50,000 at time of randomization

12. Patients with an Absolute neutrophil count (ANC) of < 1,000 or White Blood Count (WBC) of <2,000 at time of randomization

13. Patients with hemoglobin <6g/dL

14. Patients who are unable to take oral medication at time of randomization

15. Patients with clinically significant systemic infection requiring active use of IV antibiotics, anti-virals, or anti-fungals

16. 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

17. Known intolerance to tacrolimus or everolimus or Myfortic.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Zimmerman, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Denver

Aurora, Colorado, United States

Countries

United States

Other Identifiers

CRAD001HUS63T

Identifier Type: -

Identifier Source: secondary_id

12-0457

Identifier Type: -

Identifier Source: org_study_id