Recruiting

Phase 2

EverolimusEverolimus Post Orthotopic Liver Transplant

Sponsor:

Tomoaki Kato

Code:

NCT01998789

Conditions

Orthotopic Liver Transplant

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Everolimus

Standard Tacrolimus

Study Details

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

Study ID

NCT01998789

Start date

Oct, 2013

Status verified date

Aug, 2017

Completion date

Feb, 2019

Anticipated

Primary completion date

Jun, 2018

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Ability and willingness to provide informed consent and adhere to study regimen
Recipients of primary liver transplant from deceased or living donor
18 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

Key Exclusion Criteria:

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)

Key Exclusion-Baseline/ Randamization

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)
The presence of thrombosis via Doppler ultrasound of the major hepatic arteries, major hepatic veins, portal vein and inferior vena cava.
Presence of clinically significant wound

Study Design

Enrollment

50 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Everolimus Conversion Arm

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.

active comparator: Standard Tacrolimus Immunosuppresion Arm

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.

Interventions

Everolimus

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

Standard Tacrolimus

Primary outcome measure

Change in estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline and 12 months post transplant ]

Central Contacts and Locations

Central contacts

Theresa Lukose, PharmD

tt2103@columbia.edu

Marcela Laurito, MD

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

Locations

Columbia University Medical Center-NYPH

Recruiting

New York, New York, United States, 10032

Contacts

Tomoaki Kato, M.D

tk2388@columbia.edu

Theresa Lukose, PharmD

tt2103@columbia.edu

Principal Investigator:

Tomoaki Kato, MD

More Information

Sponsor

Tomoaki Kato

Last update posted

Aug 10, 2017

Last verified

Aug, 2017

Keywords

Liver Transplantation
Everolimus
Immunosuppression

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Tomoaki Kato on 2017-08-10.