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Myfortic in High MELD Liver Transplantation

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ClinicalTrials.gov Identifier: NCT01807767
Recruitment Status : Completed
First Posted : March 8, 2013
Last Update Posted : August 10, 2015
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

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.

Condition or disease Intervention/treatment Phase
High Model for End-Stage Liver Disease (MELD) Score Drug: Everolimus, Myfortic and Tacrolimus Drug: Myfortic and Tacrolimus Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Evaluation of the Efficacy and Safety of Zortress (Everolimus)/Myfortic (Enteric Coated Mycophenolate Sodium) Conversion in High MELD Liver Transplantation
Study Start Date : March 2013
Actual Primary Completion Date : July 2015
Actual Study Completion Date : August 2015


Arm Intervention/treatment
Experimental: 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

Drug: 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

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

Myfortic and Tacrolimus
Normal Care: Myfortic BID 360-720 mg Tacrolimus (5-12ng/mL)
Drug: Myfortic and Tacrolimus
Myfortic BID 360-720 mg Tacrolimus (5-12ng/mL)
Other Names:
  • Myfortic: CellCept
  • Tacrolimus: FK-506, fujimycin, Prograf, Advagraf, Protopic




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01807767


Locations
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United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
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Principal Investigator: Michael Zimmerman, MD University of Colorado, Denver

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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01807767     History of Changes
Other Study ID Numbers: 12-0457
CRAD001HUS63T
First Posted: March 8, 2013    Key Record Dates
Last Update Posted: August 10, 2015
Last Verified: August 2015

Additional relevant MeSH terms:
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Mycophenolic Acid
Liver Diseases
End Stage Liver Disease
Digestive System Diseases
Liver Failure
Hepatic Insufficiency
Tacrolimus
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antibiotics, Antitubercular
Antitubercular Agents