ISCHEMIC REPERFUSION INJURY AFTER LIVER TRANSPLANTATION: HEPATIC ISCHEMIA AND REPERFUSION INJURY REPRESENTS THE MAIN UNDERLYING MECHANISM FOR GRAFT DYSFUNCTION, AND FAILURE, POST-TRANSPLANTATION. HYPOXIA AND REPERFUSION ACTIVATE INNATE MECHANISMS OF INFLAMMATION THAT CAUSES INJURY AND UNDERLINE DELAYED GRAFT FUNCTION. IT CAUSES ALMOST 10% OF EARLY ORGAN FAILURE, AND CAN LEAD TO THE HIGHER INCIDENCE OF BOTH ACUTE AND CHRONIC REJECTION. MedDRA version: 21.1 Level: PT Classification code 10063837
Conditions
Interventions
Trade Name: SIMVASTATINA SANDOZ - 40 MG COMPRESSE RIVESTITE CON FILM 28 COMPRESSE IN BLISTER PVC/AL
Product Name: SIMVASTATINA 40 mg capsule
Product Code: SIMVA
Pharmaceutical Form: Capsule, hard
INN
Sponsors
ISTITUTO MEDITERRANEO PER I TRAPIANTI E TERAPIE AD ALTA SPECIALIZZAZIONE - ISMETT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) PATIENT (MALE AND FEMALE) OVER 18 YEARS OF AGE. 2) DECEASED BRAIN DONOR (MALE AND FEMALE) OVER 18 YEARS OF AGE. 3) THE FEMALE PATIENTS IN POTENTIALLY ABLE TO TAKE A PREGNANCY UNDERTAKE TO ENSURE EFFECTIVE PRACTICE OF BIRTH CONTROL DURING THE FIRST 6 MONTHS OF STUDY AFTER THE WHOLE LIVER TRANSPLANT. 4) PATIENT WITH LIVER DISEASE AT THE STADIUM OR TERMINAL CANCER LIVER DISEASE, AND SUITABLE CANDIDATE PLACED IN WAITING LIST FOR LIVER WHOLE PRIMARY AT ISMETT. 5) PATIENT UNDERWENT LIVER TRANSPLANTATION FROM DECEASED BRAIN DONORS (NOT IDENTICAL HLA) COMPATIBLE IN TERMS OF BLOOD GROUP ABO. 6) PATIENT CAN UNDERSTAND THE PURPOSE AND RISKS OF THE STUDY, WHICH HAS BEEN FULLY INFORMED AND GIVING WRITTEN INFORMED CONSENT. 7) PATIENT UNABLE TO WRITE AND / OR READ, BUT THAT IS FULLY CAPABLE OF UNDERSTANDING ORAL PROPOSAL BY THE RESEARCHER (OR THE APPOINTED REPRESENTATIVE) AND GIVING INFORMED CONSENT FOR ORAL TESTIFIED IN WRITING BY AN INDEPENDENT THIRD PERSON. 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 106 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: THE FOLLOWING SUBJECTS WILL BE EXCLUDED BY DONOR POPULATION: (1) PREGNANT OR BREAST-FEEDING DONORS, (2) ALLERGIC DONOR OR WITH AUTOIMMUNE DISEASE. (3) DONOR REQUIRES ONGOING DOSING WITH A SYSTEMIC IMMUNOSUPPRESSIVE DRUG AT HARVESTING PROCEDURES. (4) DONOR KNOWN TO BE HIV POSITIVE. (5) DONOR WITH MALIGNANCY OR HISTORY OF MALIGNANCY, EXCEPT NON-METASTATIC BASAL OR SQUAMOUS CELL CARCINOMA OF THE SKIN THAT HAS BEEN TREATED SUCCESSFULLY. (6) DONOR HAS PREVIOUSLY RECEIVED OR IS RECEIVING AN ORGAN TRANSPLANT. THE FOLLOWING SUBJECTS WILL BE EXCLUDED BY RECIPIENT POPULATION: (1) RECIPIENTS WITH ACUTE LIVER DISEASE, (2) PEDIATRIC PATIENTS OR PEDIATRIC DONORS, (3) PATIENTS UNDERGOING RE-LT, (4) PATIENTS UNDERGOING SPLIT OR LIVING DONOR LIVER TRANSPLANTATION, (5) PATIENTS UNDERGOING COMBINED LIVER- OR OTHER SOLID (ABDOMINAL OR THORACIC) ORGAN(S) TRANSPLANTATION, (6) PATIENT WHO IS PARTICIPANTING OR HAVE BEEN PARTICIPATED TO ANOTHER CLINICAL TRIAL/STUDY AND/OR WHICH HAVE ASSUMED AN EXPERIMENTAL DRUG IN THE LAST 30 DAYS. (7) ANY CLINICALLY RELEVANT CONDITIONS THAT MIGHT AFFECT STUDY PARTICIPATION AND/OR STUDY RESULTS, (8) PATIENT WITH HISTORY OF ALLERGY OR INTOLLERANCE TO STATINS. (9) PATIENTS WITH HISTORY OF SUBSTANCE ABUSE, AND / OR PSYCHIATRIC DISORDERS OR CONDITIONS THAT MAY INVALID THE COMMUNICATION WITH INABILITY TO UNDERSTAND THE POTENTIAL RISKS AND BENEFITS OF THE STUDY.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: TO EVALUATE THE EFFICACY OF SIMVASTATIN INTRAGASTRIC ADMINISTRATION USING A NASO-GASTRIC CANNULA IN ADDITION TO COLD-STORAGE FOR PREVENTING ISCHEMIA/REPERFUSION INJURIES. WE WILL COMPARE 3-MONTH, 6-MONTH AND 12-MONTH GRAFT SURVIVAL AFTER LIVER TRANSPLANTION, IN ORDER TO IDENTIFY A SIGNIFICANT RELATION INTO TWO HOMOGENOUS GROUPS OF LIVER TRANSPLANTED PATIENTS, ONLY DIFFERENT FOR SIMVASTATIN OR NOT ADMINISTRATION REGIMEN; USING THE SAME PROCEDURE, WITH IDENTICAL SURGICAL INSTRUMENTS, AND MEDICAL AND NURSING SKILLED STAFF.;Secondary Objective: TO EVALUATE THE EFFICACY OF SIMVASTATIN ADDITION TO COLD-STORAGE IN PREVENTING ISCHEMIA/REPERFUSION INJURIES. WE WILL COMPARE 3-MONTH, 6- MONTH AND 12-MONTH PATIENT SURVIVAL, HOSPITALIZATION STAYS AND ALL TRANSPLANT-RELATED COMPLICATIONS IN TERMS OF THE MULTI-TIER CLAVIEN GRADING SYSTEM AFTER LIVER TRANSPLANTION, IN ORDER TO IDENTIFY A SIGNIFICANT RELATION INTO TWO HOMOGENOUS GROUPS OF LIVER TRANSPLANTED PATIENTS, ONLY DIFFERENT FOR SIMVASTATIN OR NOT ADMINISTRATION REGIMEN; USING THE SAME PROCEDURE, WITH IDENTICAL SURGICAL INSTRUMENTS, AND MEDICAL AND NURSING SKILLED STAFF.;Primary end point(s): POST-TRANSPLANT LIVER ALLOGRAFT SURVIVAL;Timepoint(s) of evaluation of this end point: 3-MONTH, 6-MONTH, 1-YEAR POST-TRANSPLANT LIVER ALLOGRAFT SURVIVAL | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): POST-LIVER TRANSPLANT PATIENT SURVIVAL; INCIDENCE OF ADVERSE EVENT DURING THE POST-LIVER TRANSPLANT COURSE; DIFFERENCES IN TRANSAMINASES (ALT, AST, GGT, ALP), INTERNATIONAL NORMALIZED RATIO (INR), AND BILIRUBIN (TOTAL AND DIRECT) DURING THE POST-TRANSPLANT COURSE; LENGTHS OF HOSPITAL AND INTENSIVE CARE UNIT STAYS; CLAVIEN CLASSIFICATION WILL BE USED TO EVALUATE POSTOPERATIVE EVENTS AFTER TRANSPLANTATION (SURGICAL AND MEDICAL COMPLICATIONS, INCLUDING INFECTIONS).;Timepoint(s) of evaluation of this end point: 3-MONTH, 6-MONTH, 1-YEAR POST-TRANSPLANT COURSE; 3-MONTH, 6-MONTH, 1-YEAR POST-TRANSPLANT COURSE; POST-OPERATIVE DAYS 1, 2, 7, 15, 30, 90, 120, 360, 540.; LENGTHS OF HOSPITAL AND INTENSIVE CARE UNIT STAYS; POSTOPERATIVE EVENTS IN THE FIRST 3 AND 6 MONTHS AFTER TRANSPLANTATION (SURGICAL AND MEDICAL COMPLICATIONS, INCLUDING INFECTIONS) | — |
Countries
Italy
Contacts
Public ContactFRANCESCA VENUTI
IRCCS/ISMETT
Outcome results
None listed