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Efficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients

Information source: Novartis
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Liver Transplantation

Intervention: Tacrolimus (reduced tacrolimus) (Drug); Tacrolimus (tacrolimus elimination) (Drug); Tacrolimus (tacrolimus control) (Drug); Everolimus (reduced tacrolimus) (Drug); Everolimus (tacrolimus elimination) (Drug); Corticosteroids (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Novartis Pharmaceuticals

Official(s) and/or principal investigator(s):
Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals

Summary

This trial was designed to address important issues that impact recipients of liver allografts as well as clinicians, ie, renal function, reduction or discontinuation of tacrolimus early post-transplantation, and progression rate of fibrosis in hepatitis C virus (HCV) positive patients.

Clinical Details

Official title: A 24 Month, Multicenter, Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Incidence Rate of Composite Efficacy Failure From Randomization to Month 12

Secondary outcome:

Incidence Rate of Composite Efficacy Failure From Randomization to Month 24

Incidence Rate of Treated Biopsy Proven Acute Rejection (tBPAR) at Months 12 and 24

Change in Renal Function From Randomization to Months 12 and 24

Detailed description: This 24-month study consisted of a screening period, a baseline period (3 to 7 days post-transplantation) followed by a run-in period that ended on the day of randomization at 30 days (± 5 days) post-transplantation. Patients were screened for eligibility prior to liver transplantation. Patients who had undergone successful liver transplantation were initiated on a tacrolimus-based regimen that included corticosteroids and entered the baseline period (between 3 and 7 days post-transplantation). At 30 (± 5) days post-transplantation, patients who met additional randomization inclusion/exclusion criteria were randomized into the study.

Eligibility

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Ability and willingness to provide written informed consent and adhere to study

regimen.

- Recipients who are 18-70 years of age of a primary liver transplant from a deceased

donor.

- Recipients who have been initiated on an immunosuppressive regimen that contains

corticosteroids and tacrolimus, 3-7 days post-transplantation.

- Confirmed recipient hepatitis C virus (HCV) status at Screening (either by antibody

or by PCR (polymerase chain reaction).

- Allograft is functioning at an acceptable level by the time of randomization as

defined by protocol specific laboratory values.

- Abbreviated Modification of Diet in Renal Disease estimated glomerular filtration

rate (MDRD eGFR) ≥ 30 mL/min/1. 73m2. Results obtained within 5 days prior to randomization are acceptable, however, no sooner than Day 25 post-transplantation.

- Verification of at least 1 tacrolimus trough level of ≥ 8 ng/mL in the week prior to

randomization. Investigators should make adjustments in tacrolimus dosing to continue to target trough levels above 8 ng/mL prior to randomization. Exclusion Criteria

- Patients who are recipients of multiple solid organ or islet cell tissue transplants,

or have previously received an organ or tissue transplant. Patients who have a combined liver-kidney transplant.

- Recipients of a liver from a living donor, or of a split liver.

- History of malignancy of any organ system within the past 5 years whether or not

there is evidence of local recurrence or metastases, other than non-metastatic basal or squamous cell carcinoma of the skin, or HCC (hepatocellular carcinoma) (see next criteria).

- Hepatocellular carcinoma that does not fulfill Milan criteria (1 nodule ≤ 5 cm, 2-3

nodules all < 3 cm) at the time of transplantation as per explant histology of the recipient liver.

- Any use of antibody induction therapy.

- Patients with a known hypersensitivity to the drugs used on study or their class, or

to any of the excipients.

- Patients who are recipients of ABO incompatible transplant grafts.

- Recipients of organs from donors who test positive for Hepatitis B surface antigen or

HIV are excluded.

- Patients who have any surgical or medical condition, which in the opinion of the

investigator, might significantly alter the absorption, distribution, metabolism and excretion of study drug.

- Women of child-bearing potential (WOCBP).

- Patients with any history of coagulopathy or medical condition requiring long-term

anticoagulation which would preclude liver biopsy after transplantation. (Low dose aspirin treatment or interruption of chronic anticoagulant is allowed). Other protocol-defined inclusion/exclusion criteria may apply.

Locations and Contacts

Novartis Investigative Site, Buenos Aires C1118AAT, Argentina

Novartis Investigative Site, Buenos Aires W3400ABH, Argentina

Novartis Investigative Site, Buenos Aires C1181ACH, Argentina

Novartis Investigative Site, Gent 9000, Belgium

Novartis Investigative Site, Leuven 3000, Belgium

Novartis Investigative Site, Liege 4000, Belgium

Novartis Investigative Site, Bogotá, Colombia

Novartis Investigative Site, Cali, Colombia

Novartis Investigative Site, Medellín, Colombia

Novartis Investigative Site, Praha 4 140 21, Czech Republic

Novartis Investigative Site, Bordeaux Cedex 33076, France

Novartis Investigative Site, Clichy 92110, France

Novartis Investigative Site, Creteil 94010, France

Novartis Investigative Site, Lille 59000, France

Novartis Investigative Site, Marseille 13385, France

Novartis Investigative Site, Montpellier 34295, France

Novartis Investigative Site, Villejuif 94805, France

Novartis Investigative Site, Berlin 13353, Germany

Novartis Investigative Site, Essen 45147, Germany

Novartis Investigative Site, Hamburg 20246, Germany

Novartis Investigative Site, Heidelberg 69120, Germany

Novartis Investigative Site, Jena 07740, Germany

Novartis Investigative Site, Leipzig 04103, Germany

Novartis Investigative Site, Mainz 55131, Germany

Novartis Investigative Site, Regensburg 93053, Germany

Novartis Investigative Site, Budapest 1082, Hungary

Novartis Investigative Site, Dublin 4, Ireland

Novartis Investigative Site, Jerusalem 91120, Israel

Novartis Investigative Site, Tel-Aviv 64239, Israel

Novartis Investigative Site, Pisa 56124, Italy

Novartis Investigative Site, Rotterdam 3015 CE, Netherlands

Novartis Investigative Site, Moscow 123182, Russian Federation

Novartis Investigative Site, Moscow 129010, Russian Federation

Novartis Investigative Site, Madrid 28007, Spain

Novartis Investigative Site, Stockholm 141 86, Sweden

Novartis Investigative Site, Edinburgh ED16 4SA, United Kingdom

Novartis Investigative Site, London SE5 9RS, United Kingdom

Novartis Investigative Site, Edmonton, Alberta T6G 2B7, Canada

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Novartis Investigative Site, San Martin, Buenos Aires C1107BEA, Argentina

Novartis Investigative Site, Los Angeles, California 90033, United States

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Novartis Investigative Site, Detroit, Michigan 48202-2689, United States

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Novartis Investigative Site, London, Ontario N6A 5A5, Canada

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Novartis Investigative Site, Baracaldo, País Vasco 48903, Spain

Novartis Investigative Site, Philadelphia, Pennsylvania 19107, United States

Novartis Investigative Site, Rio de Janeiro, RJ 21041-030, Brazil

Novartis Investigative Site, Roma, RM 00161, Italy

Novartis Investigative Site, Porto Alegre, RS 90020-090, Brazil

Novartis Investigative Site, Blumenau, SC 89010-500, Brazil

Novartis Investigative Site, Ribeirao Preto, SP 14048-900, Brazil

Novartis Investigative Site, São Paulo, SP 01323-900, Brazil

Novartis Investigative Site, Rosario, Santa Fe C2000DSR, Argentina

Novartis Investigative Site, Bedford Park, South Australia 5042, Australia

Novartis Investigative Site, Charleston, South Carolina 29425, United States

Novartis Investigative Site, Torino, TO 10126, Italy

Novartis Investigative Site, Nashville, Tennessee 37232, United States

Novartis Investigative Site, Dallas, Texas 75208-2312, United States

Novartis Investigative Site, Dallas, Texas 75246, United States

Novartis Investigative Site, Houston, Texas 77030-2400, United States

Novartis Investigative Site, Houston, Texas 77030, United States

Novartis Investigative Site, Heidelberg, Victoria 3084, Australia

Novartis Investigative Site, Nedlands, Western Australia 6009, Australia

Additional Information

Starting date: January 2008
Last updated: May 17, 2013

Page last updated: August 23, 2015

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