Open label multicentre randomized trial comparing standard immunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen in combination with everolimus in the novo renal transplantation in elderly patients.
- Conditions
- immunosuppression10029149Renal transplantation
- Registration Number
- NL-OMON48113
- Lead Sponsor
- niversitair Medisch Centrum Groningen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 351
nclusion 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
Exclusion criteria for both stratum A and B 1. Subject is a multi-organ
transplant recipient 2. Recipient of 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 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 LFTs (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 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 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primay outcome is succesfull transplantation. As outcome is expected to be<br /><br>markedly different in stratum A and stratum B, different primary outcome<br /><br>criteria will be used. We have defined successful transplantation as our<br /><br>primary outcome variable combining patient and graft survival with a minimum<br /><br>level of renal function. In our opinion this endpoint combines the most<br /><br>relevant outcomes for the patient. Stratum A: Primary endpoint: successful<br /><br>transplantation at 1 year after transplantation defined as: absence of graft or<br /><br>patient loss in the presence of an eGFR above 30 ml/min/1.73m2. Stratum B:<br /><br>Primary endpoint: successful transplantation at 1 year after transplantation<br /><br>defined as absence of graft or patient loss in the presence of an eGFR above 45<br /><br>ml/min/ 1.73m2. Both strata are pooled for analysis. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary outcomes both strata: • Incidence of individual endpoints of death,<br /><br>graft loss, rejection eGFR below 30 or 45 ml/min/ 1.73m2 rejection at Months 12<br /><br>and 24. • Rejection treatment and type of rejection treatment • The evolution<br /><br>of renal function (eGFR) over time by slope analysis. • The incidence of<br /><br>adverse events, serious adverse events and adverse reactions • The incidence of<br /><br>clinically relevant infections, new onset diabetes mellitus and malignancies •<br /><br>Presence of frailty at 3, 12 and 24 months after transplantation and change in<br /><br>frailty from baseline •Presence of markers for immunosenescence at 12 and 24<br /><br>months and changes from baseline •hrQOL at 3, 12 and 24 months and changes from<br /><br>baseline. •Development of donor specific antibodies. </p><br>