PROPHYLAXIS OF ALLOGRAFT REJECTION AFTER RENAL TRASPLANT. MedDRA version: 19.0 Level: PT Classification code 10038533 Term: Renal transplant System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Trade Name: Prograf
Product Name: Prograf
Pharmaceutical Form: Capsule
INN or Proposed INN: TACROLIMUS
CAS Number: 104987-11-3
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Sponsors
HOSPITAL UNIVERSITARI DE BELLVITGE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Adult patients (? 18 years). ? Recipients of a renal graft from a cadaveric or living donor with more than 6 months post-transplant evolution. ? Patients who received a non-interrupted stable oral dose of immediate release tacrolimus (Prograf / Adoport®) and have had stable TAC trough concentrations between 6-10ng / ml for at least 10 days (steady state conditions). ? Patients receiving allowed concomitant immunosuppressive medication : mofetil or sodium mycophenolate and corticosteroids. ? May receive induction therapy with basiliximab. ? Subjects must be willing to give written informed consent for the trial. If a subject can not give written informed consent, a legal representative can sign instead. ? Women of childbearing potential should have a negative pregnancy test result at the time of inclusion and accept the use of a medically acceptable method of contraception during the selection and while receiving medication specified in the protocol. 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 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: ? Patients on dialysis or treatment of rejection after transplantation. ? Patients treated with substances with potential interaction with TAC, particularly potent inhibitors of CYP3A4 (such as telaprevir, boceprevir, ritonavir, ketoconazole, voriconazole, itraconazole, telithromycin or clarithromycin) or inducers of CYP3A4 (such as rifampin or rifabutin). ? Patients with induction therapy with ATG or rituxumab. ? Patients participating in another clinical trial or who were treated with any investigational drug within 30 days prior to inclusion. ? Patients with liver disease. ? Patient or donor with a current diagnosis or history of malignancy within the last 5 years except non-metastatic basal or squamous cell skin carcinoma successfully treated. ? Pregnant or lactating women and all women of childbearing potential unless they use reliable contraception. A pregnancy test will be performed in the selection and end of the study. ? Recipient of any other organ apart from kidney. ? Recipients of bone marrow or stem cell transplant. ? Recipients of a kidney from a ABO incompatible donor. ? Patients with donor specific anti-HLA antibodies. ? Anticipated cold ischemia time of ? 24 hours. ? Patients with a concomitant uncontrolled infection, systemic infection requiring treatment, or any other unstable medical condition that may interfere with the study objectives. ? Patients with severe diarrhea, vomiting, active peptic ulcer or gastrointestinal disorder that may affect the absorption of TAC. ? Patients with white blood cell count ? 2.8 x 109 / L unless the absolute neutrophil count (ANC) is ? 1.0 x 109 / L ? Patients with platelet count ? 50 x 109 / L. ? Patients with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) exceeding> 3 times the upper limit of normal during the 30 days prior to the transplant procedure. ? Patients with known hypersensitivity to TAC or any of the excipients in the formulation ? Patients unable to swallow study medication. ? Patients with any form of current substance abuse, psychiatric disorder or a condition that, in the investigator's opinion, may invalidate the communication with the investigator. ? Patients who require a high intake of potassium or potassium-sparing diuretics. ? Patients treated with substances with known nephrotoxic or neurotoxic effects. ? Recipients that are positive for hepatitis C virus (HCV-RNA positive) and / or hepatitis B virus (HBV DNA or HBsAg positive). ? Recipients positive for human immunodeficiency virus (HIV-Ab positive). ? Patients unable to understand the effects and risks of the study, who can not give informed consent in writing, or who are unwilling to comply with the study protocol patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess whether the optimization of the dosage of Tac in renal transplant patients, based on a population pharmacokinetic model previously developed that includes the CYP3A5 * 3 and CYP3A4 * 22 polymorphisms and hematocrit (as responsible for some of the variability in exposure to Tac) significantly increases the percentage of patients in therapeutic target with a margin of 30% superior, compared to standard dosing Tac. The percentage of patients in therapeutic target after 5 oral doses of Tac after the first dose post-transplant (defined as therapeutic Diana Co: 6-10 ng / ml) will be evaluated.;Secondary Objective: 1. Pharmacokinetic variables - Co at day 6, 10, 15, 30, 60 and 90 after the start of post transplant tacrolimus. - Time to achieve the therapeutic target. - Number of dose modifications to achieve the therapeutic target. 2. Clinical variables: - Severity of delayed graft function defined as the number of dialysis sessions required after transplantation. - Protocol biopsies at 3 months follow-up. The presence of sub-clinical rejection or nephrotoxicity by calcineurin will be studied. - Incidence of biopsy-confirmed acute rejection. - Renal function at days 30, 60 and 90 after the start of post transplant tacrolimus. - Loss of graft. - EXITUS 3. Pharmaco-economic variables. Analysis of drug-economic impact of dose adjustment depending on the model of population kinetics.;Primary end point(s): Measurement of plasma concentration of tacrolimus. Pre-dose samples will be obtained after reaching the Steady State, at the following times: after 5 doses of oral Tac after the first dose post-transplant on day 6 and on day 10 , 15, 30, 60 and 90 after initiation of treatment.;Timepoint(s) of evaluation of this end point: 90 days after the initiation of tacrolimus | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Time to achieve the therapeutic target within the 90 days follow-up period. ? Number of dose modifications necessary to achieve the target. ? Efficacy endpoints. Delayed graft function severity defined by the number of dialysis sessions required after transplantation, incidence of acute rejection confirmed by biopsy, incidence of subclinical rejection, incidence of CNI nephrotoxicity, renal function, graft loss and exitus will be evaluated. ? Security Settings The incidence of adverse events and serious adverse events, including acute rejection, will be evaluated.;Timepoint(s) of evaluation of this end point: 90 days after the initiation of tacrolimus | — |
Countries
Spain
Contacts
Public ContactCAROLINA POLO
INSTITUT DE RECERBA BIOMÈDICA DE BELLVITGE-IDIBELL
Outcome results
None listed