Study to evaluate renal function of everolimus plus tacrolimus in liver transplant patients
- Conditions
- liver transplantationMedDRA version: 20.0Level: LLTClassification code 10024716Term: Liver transplantationSystem Organ Class: 100000004865Therapeutic area: Body processes [G] - Immune system processes [G12]
- Registration Number
- EUCTR2011-003118-17-DE
- Lead Sponsor
- ovartis Pharma GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria
1. Patients who are willing and able to participate in the study and from whom written
informed consent has been obtained.
2. Male or female recipients of a full-size liver allograft, aged 18 to 65 years.
3. Females capable of becoming pregnant must have a negative pregnancy test prior to start
of study and before randomization and are required to practice a medically approved
method of birth control or live in total abstinence for the duration of the study.
Inclusion Criteria - Randomization
1. eGFR (MDRD4 formula) > 30 mL/min/1.73m2 at time of randomization.
2. Absence of thrombosis via Doppler ultrasound of the major hepatic arteries, major hepatic
veins, portal vein and inferior vena cava at time of randomization and prior to any
initiation of treatment with everolimus.
3. Allograft is functioning at an acceptable level by the time of randomization as defined total bilirubin levels =3 times ULN and AlkP, AST, ALT levels = 5 times ULN.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 220
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110
Exclusion Criteria:
1. HIV positive patients.
2. Patients who are recipients of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant.
3. Patients with renal failure or CKD/ESRD who require renal replacement therapy for more than 2 weeks prior to transplantation.
4. 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 (see next criteria).
5. HCC that does not fulfill Milan criteria (1 nodule = 5 cm, 2-3 nodules all = 3 cm) at the time of transplantation.
6. Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients.
7. Patients receiving drugs known to significantly interact with any immunosuppressant used in the trial.
8. Patients who are recipients of AB0 incompatible transplant grafts.
9. Patients with a current systemic infection or sepsis requiring active use of IV antibiotics.
10. Patients with symptoms of significant mental illness and with inability to cooperate or communicate with the investigator. Patients who are unlikely to comply with the study requirements, or who are unable to give informed consent.
11. Women
- who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml))
- who are menstruating and capable of becoming pregnant and not practicing a medically approved method of contraception (Pearl Index <1) during and up to at least 4-8 weeks after the end of treatment. A negative pregnancy test (serum) for all women entering menarche is required with sufficient lead time before inclusion
12. Patients, who have already been randomized into this study earlier must not be included a second time.
13. Participation in another clinical trial.
Exclusion Criteria - Randomization
1. Patients who are not able to take oral medication at time of randomization.
2. Patients with platelet count <50,000/mm³)
3. Patients with an absolute neutrophil count of <1,000/mm³
4. Patients with a white blood cell count of <2,000/mm³),
5.Patients with hemoglobin < 6.0 g/dL (transfusion of erythrocytes concentrate during or after transplantation are allowed according to investigator discretion)
6.Patients with uncontrolled hypercholesterolemia (>350mg/dL; >9mmol/L) or
hypertriglyceridemia (>300 mg/dL, >8.5 mmol/L).
7.Patients with a protein/creatinine ratio indicating daily urinary protein excretion >1 g/24h
at time of randomization.
8.Patients with clinically significant or uncontrolled systemic infection requiring active use
of IV antibiotics at the time of randomization.
9.Patients who have received an investigational drug within 30 days prior to randomization.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate that an immunosuppressive regimen based on everolimus (EVR) in co-exposure with tacrolimus (TAC) has superior efficacy compared to tacrolimus alone on estimated glomerular filtration rate (MDRD-4 formula) at Month 12 in de novo liver transplant recipients.;Secondary Objective: Key secondary objective:<br><br>To evaluate the incidence of a composite of treated biopsy proven acute rejection (BPAR), graft loss or death at Month 12.<br><br>;Primary end point(s): The primary objective of the trial is to demonstrate that an immunosuppressive regimen based on everolimus (EVR) in co-exposure with tacrolimus (TAC) has superior efficacy compared to tacrolimus alone on estimated glomerular filtration rate (MDRD-4 formula) in de novo liver transplant recipients.;Timepoint(s) of evaluation of this end point: 12 months after transplantation
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • efficacy-related endpoints, such as acute rejection, treated biopsy proven acute rejection (BPAR), graft loss, death and loss to follow-up (as composites or individual endpoints)<br>• endpoints related to renal function: eGFR using various methods (MDRD-4, Nankivell, Cockcroft-Gault, CKD EPI and Hoek formulae<br><br><br>;Timepoint(s) of evaluation of this end point: 12 months after transplantation