Everolimus Post Orthotopic Liver Transplant

NCT01998789 | Unknown Phase 2 FDA Drug

• 1 other identifier: AAAL1602
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy of an everolimus conversion (EVR) protocol as compared to the standard tacrolimus (TAC) based protocol in liver transplant recipients, as determined by renal function, rejection rates, and progression to fibrosis (in HCV positive subjects). Additionally, safety profile and tolerability of these regimens will be assessed.

Conditions

Orthotopic Liver Transplant

Keywords

Liver Transplantation; Everolimus; Immunosuppression

Outcome Measures

Primary Outcomes (1)

• Change in estimated Glomerular Filtration Rate (eGFR)

  Comparison of change in Renal function, as measured by eGFR from baseline to 12 months post liver transplantation, in subjects maintained on an everolimus conversion regimen versus those maintained on a standard tacrolimus based regimen.

  Baseline and 12 months post transplant

Secondary Outcomes (4)

• Change in estimated Glomerular Filtration Rate (eGFR)

  Baseline and 24 months post liver transplantation

• Proportion of HCV patients who develop stage 2 of 4 or greater fibrosis, liver failure, or fibrosing cholestatic hepatitis (FCH) at month 12 and 24

  Up to 24 months post liver transplantation

• Composite Efficacy Failure Rate

  Up to 24 months

• Incidence of Hepatocellular Carcinoma (HCC) Recurrence

  Up to 12 months post transplant

Study Arms (2)

Everolimus Conversion Arm

EXPERIMENTAL

Everolimus will be initiated within 24 hours of baseline at a dose of 1 mg po BID (2 mg/day). Therapeutic Drug Monitoring will be performed throughout the study. Tacrolimus should be eliminated when the everolimus target range has been reached. Complete tacrolimus elimination will not occur earlier than 90 days post transplant and no later than 120 days post transplant. Enteric coated mycopenolic acid will be maintained for the duration of the study. Oral corticosteroids may not be eliminated sooner than 180 days post transplantation. Everolimus doses will be adjusted based on local lab results of everolimus trough levels.

Drug: Everolimus

Standard Tacrolimus Immunosuppresion Arm

ACTIVE COMPARATOR

Subjects will be maintained on standard maintenance immunosuppression per local protocol, consisting of a tacrolimus plus enteric coated mycophenolic acid. Oral corticosteroids may not be eliminated sooner than 180 days post transplantation. Tacrolimus doses will be adjusted based on local lab results of tacrolimus trough levels.

Drug: Standard Tacrolimus

Interventions

Everolimus DRUG

Everolimus will be initiated within 24 hours of baseline at a dose of 1 mg po BID (2 mg/day).

Also known as: Zortress

Everolimus Conversion Arm

Standard Tacrolimus DRUG

Subjects will be maintained on standard maintenance immunosuppression per local protocol, consisting of a tacrolimus plus enteric coated mycophenolic acid. Oral corticosteroids may not be eliminated sooner than 180 days post transplantation. Tacrolimus doses will be adjusted based on local lab results of tacrolimus trough levels.

Also known as: Prograf

Standard Tacrolimus Immunosuppresion Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability and willingness to provide informed consent and adhere to study regimen
• Recipients of primary liver transplant from deceased or living donor
• years of age or greater
• Lab Model For End-Stage Liver Disease (MELD) score ≤ 30
• Abbreviated Modification of Diet in Renal Disease (MDRD) eGFR ≥ 30 mL/min/1.73

You may not qualify if:

• Recipient of multiple solid or organ transplant, or have previously received and organ transplant
• Women of child-bearing potential unless they are willing to participate in adequate contraception methods as outlined in the study.
• HIV infection (results obtained 6 months prior to screening is acceptable)
• Severe hypercholesterolemia (\> 350 mg/dL) or hypertriglyceridemia (\> 500 mg/dL) within 30 days prior to baseline.
• Thrombocytopenia (platelets \< 50,000/mm3)
• Absolute neutrophil count of \< 1000/mm3 or white blood cell count of \< 2000/mm3
• Subjects in a critical care unit requiring life support measures such as mechanical ventilation, dialysis, requirement of vasopressor agents
• Liver allograft is functioning at an unacceptable level as defined by the Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Total Bilirubin levels \> 3 times upper limit of normal (ULN) and Alkaline Phosphatase (AlkP) and Gamma-glutamyltransferase (GGT) levels \> 5 times ULN
• Diagnosis of autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis
• Hepatocellular carcinoma with evidence of macrovascular invasion on explanted liver or evidence of extrahepatic spread
• Inability to take medications by mouth
• Renal insufficiency, as defined by abbreviated MDRD eGFR \< 30 mL/min/1.73m2, or requirement of dialysis, that does not recover prior to baseline
• Episode of acute rejection requiring antibody therapy or more than one steroid treated episode of acute rejection
• Subjects with a confirmed spot urine protein/creatinine ratio that indicates ≥1g/24h of proteinuria.
• Subtherapeutic trough levels of tacrolimus during the week prior to baseline (subject must have at least one tacrolimus level ≥ 8 ng/mL)

Sponsors & Collaborators

• Tomoaki Kato: lead

Study Sites (1)

Columbia University Medical Center-NYPH

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Interventions

Everolimus; Tacrolimus

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Tomoaki Kato, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Theresa Lukose, PharmD

CONTACT

tt2103@columbia.edu

Marcela Laurito, MD

CONTACT

212-305-3839; ml3727@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Division of Abdominal Organ Transplantation

Study Record Dates

• First Submitted: November 25, 2013
• First Posted: December 2, 2013
• Study Start: October 1, 2013
• Primary Completion: June 1, 2018
• Study Completion: February 1, 2019
• Last Updated: August 10, 2017

Record last verified: 2017-08

Locations

US (1)