Hepatic transplant
Conditions
Interventions
Trade Name: Sandimmun Neoral
Product Name: Ciclosporin
Product Code: NA
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: CICLOSPORIN
CAS Number: 59865-13-3
Current Sponsor code: FFIS-INM-2017-0
Sponsors
Fundación para la Formación e Investigación Sanitarias de la Región de Murcia
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - To be 18 years of age or older -liver transplant recipient three years ago or earlier -To be in immunosuppressive therapy including cyclosporine, tacrolimus, MMF, steroids or Everolimus. -Have a normal liver function in the last year (defined as normality of transaminases and alkaline phosphatase in all laboratory tests carried out during the past year); and. Not having suffered acute rejection in the last year and not to suffer currently from chronic rejection; - Any indication of liver transplantation, except for those of autoimmune etiopathogenesis (primary biliary cirrhosis, autoimmune hepatitis and primary sclerosing cholangitis) or those transplanted for diseases of viral etiology with active viral replication -Patients who offer sufficient guarantees of adherence to the protocol -Patients who give written informed consent to participate in the study -Patients with liver transplant without minimization of IS: those who are being treated with Cyclosporine are with cyclosporinemia levels greater than 50 ng / ml; those patients who are being treated with Tacrolimus are with blood tacrolimus levels higher than 5 ng / ml -Patients with liver transplantation and minimization of IS: those who receive immunosuppression without calcineurin inhibitors, those who are being treated with Cyclosporine have levels of cyclosporinemia equal to or less than 50 ng / ml or patients who under treatment with Tacrolimus have levels of tacrolimus in blood equal to or less than 5 ng / ml 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 324 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: - Trasplante de otro órgano no hepático -Trasplante hepático por una enfermedad de etiopatogenia autoinmune (cirrosis biliar primaria, Colangitis esclerosante primaria o hepatitis autoinmune); -Pacientes con retrasplante hepático -Infección activa por el virus de la hepatitis C o por el virus de la hepatitis B -Pacientes con rechazo crónico, o rechazo agudo en el último año -Incapacidad de comprender el consentimiento informado -biopsia hepática con inflamación portal o lobulillar significativa -Pacientes con enfermedad reumática / autoinmune por la que requieran tratamiento inmunosupresor de forma mantenida.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Liver function: total proteins, albumin, bilirubin, GOT, GPT, Alkaline phosphatase, Gamma-GT, Quick index. Levels of immunosuppressants (Cyclosporinemia, tacrolimus levels). Basic hematological parameters: Hemoglobin, hematocrit, platelets and leukocytes. These markers will be analyzed monthly during the entire study, every 3 months for the following 6 months and every year thereafter up to 5 years and when clinically considered appropriate the following parameters: Every 3 months the following parameters: Metabolic parameters: glucose, uric acid, triglycerides, cholesterol, HDL-cholesterol and LDL-cholesterol; Parameters of renal function: creatinine, urea, glomerular filtration rate (MDRD), creatinine clearance; Weight, height, blood pressure, number of antihypertensive drugs, dyslipidemia, diabetes, cardiovascular complications (Angina, arrhythmias, AMI, I. Cardiac, vascular thromboembolism, peripheral artery disease), de novo neoplasms, degree of renal dysfunction G0-G5 (Document of The Spanish Society of Nephrology on the KDIGO guidelines for the evaluation and treatment of chronic kidney disease, Nefrologia 2014; 34 (3): 302-16) Baseline biopsy will be performed before starting the study in all study groups (control, minimization and withdrawal of IS and at 18 months.) To confirm the absence of rejection, the groups submitted to reduction / interruption of immunosuppression (A1, A2 and B1) will perform a liver biopsy 6 months after finalizing the changes in the SI (6 months after stopping the SI in groups A1 and B1 and 12 months after reaching the minimization of the SI in group A2). control (A3 and B2) a new biopsy will be performed 18 months after the start of the study protocol;Main Objective: Evaluate in a prospective manner whether or not withdrawal or minimisation of immunosuppression in subjects following hepatic transplant affects the clinical evolution of these subjects (cardiovascular complications, chronic renal insufficiency | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): *Clinical variables - Tolerance: Normality of liver function at least 1 year after the withdrawal of IS. Cell rejection: -Arterial hypertension. -Diabetes. -Hyperlipidemia. -States of renal function, according to GFR calculated by MDRD4 -Smoking habits - Cardiovascular Events - De novo neoplasms: Any malignant neoplasm that appears during the study 5.2.2.Study of the evolution of subpopulations of mononuclear cells in peripheral blood throughout the withdrawal of the SI. -They will be analyzed at baseline, every 3 months, at the end of the withdrawal and every 3 months up to the 18th month in all the study groups -The leukocyte populations in different stages of development of the project will be studied by means of immunofluorescence of whole blood and by flow cytometer;Timepoint(s) of evaluation of this end point: They will be analyzed at baseline, every 3 months, at the end of the withdrawal and every 3 months up to the 18th month in all the study groups | — |
Countries
Spain
Contacts
Public ContactLola Serna
FFIS
Outcome results
None listed