de novo renal transplantation in elderly patients.
Conditions
Interventions
Trade Name: everolimus
Pharmaceutical Form: Tablet
Trade Name: Envarsus
Product Name: Envarsus
Product Code: EU/1/14/935
Pharmaceutical Form: Tablet
Trade Name: Cellcept
Pharmaceutical Form:
Trade
Sponsors
UMCG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 4.2 Inclusion criteria In order to be eligible to participate in this study, a subject must meet all of the following criteria: Inclusion criteria 1. Written informed consent must be obtained before any assessment is performed 2. Male or female subject =65 years old 3. Subject randomized within 24 hours of completion of transplant surgery 4. Stratum A: Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased donor aged 65 years or older 5. Stratum B: Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased donor aged below 65 years or a living donor of any age Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 374
Exclusion criteria
Exclusion criteria: 4.3 Exclusion criteria A potential subject who meets any of the following criteria will be excluded from participation in this study Exclusion criteria for both stratum A and B 1. Subject is a multi-organ transplant recipient 2. Recipient of bloodgroup ABO incompatible allograft or CDC cross-match positive transplant 3. Subject at high immunological risk for rejection as determined by local practice for assessment of anti-donor reactivity 4. Recipient of a kidney with a cold ischaemia time (CIT) >24 hr 5. Recipients of a kidney from an HLA-identical related living donor 6. Known intolerability for one or more of the study drugs 7. Subject who is HIV positive 8. HBsAg and/or a HCV positive subject with evidence of elevated liver function tests (ALT/AST levels =2.5 times ULN). Viral serology results obtained within 6 months prior to randomization are acceptable 9. Recipient of a kidney from a donor who tests positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV) 10. Subject with a BMI greater than 35 kg/m2 11. Subject with severe systemic infections, current or within the two weeks prior to randomization 12. Subject requiring systemic anticoagulation that cannot be temporarily interrupted and which would preclude renal biopsy 13. History of malignancy of any organ system (other than localized basal or squamous cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases 14. Subject with severe restrictive or obstructive pulmonary disorders 15. Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be controlled 16. Subject with white blood cell (WBC) count = 2,000/mm3 or with platelet count = 50,000/mm3
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: The overall primary study endpoint “successful transplantation” as defined for the individual strata and analyzed for the whole study population. Stratum A: Primary endpoint: successful transplantation at two years after transplantation defined as: absence of graft or patient loss in the presence of an eGFR above 30 ml/min/1.73m2. Stratum B: Primary endpoint: successful transplantation at two years after transplantation defined as absence of graft or patient loss in the presence of an eGFR above 45 ml/min/1.73m2.;Secondary Objective: Secondary Objectives: • Successful transplantation analyzed separately per stratum The following endpoints will be analyzed in both the complete study population and the separate strata. • Incidence of individual endpoints of death, graft loss, eGFR below 30 or 45 ml/min/1.73m2 at Months 12 and 24 • Incidence of treated biopsy-proven rejection (tBPAR) • Rejection treatment and type of rejection treatment • The evolution of renal function (eGFR) over time by slope analysis • The incidence of adverse events, serious adverse events and adverse reactions • The incidence of clinically relevant infections, post transplantation diabetes mellitus, malignancies and cardiovascular events • Presence of frailty at 3, 12 and 24 months after transplantation and change in frailty from baseline • Presence of markers for immunosenescence at 12 and 24 months and changes from baseline • HRQoL at 0, 12 and 24 months and changes from baseline • Development of donor-specific anti-HLA antibodies (DSA);Primary end point(s): The overall primary study endpoint “successful transplantation” as defined for the individual strata and analyzed for the whole study population. Stratum A: Primary endpoint: successful transplantation at two years after transplantation defined as: absence of graft or patient loss in the presence of an eGFR above 30 ml/min/1.73m2. Stratum B: Primary endpoint: successful transplantation at two years after t | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Incidence of individual endpoints of death, graft loss, eGFR below 30 or 45 ml/min/ 1.73m2 at Months 12 and 24 • Incidence of treated biopsy proven rejection (tBPAR) • Rejection treatment and type of rejection treatment • The evolution of renal function (eGFR) over time by slope analysis • The incidence of adverse events, serious adverse events and adverse reactions • The incidence of clinically relevant infections, new onset diabetes mellitus, malignancies and cardiovascular events • Presence of frailty at 3, 12 and 24 months after transplantation and change in frailty from baseline • Presence of markers for immunosenescence at 12 and 24 months and changes from baseline • HRQoL at 0, 12 and 24 months and changes from baseline • Development of donor specific antibodies;Timepoint(s) of evaluation of this end point: Stratum A: it will be possible to achieve the inclusion target of 194 patients within 4 years. With an additional 2 years of follow-up the final data analysis will be possible within 6 years after initiating the study. Stratum B: on a yearly basis a mean of 97 living donor procedures and 64 deceased donor procedures. In these groups 10% of patients will not meet the inclusion criteria. With a consent rate of 70% and additional inclusion by a major Belgian transplantation center it will take 2 years to include the study population of 180 patients. With an additional 2 years of follow-up the final data analysis will be possible within 4 years after initiating the study. | — |
Countries
Netherlands
Contacts
Public ContactJ.S. Sanders
UMCG
Outcome results
None listed