To investigate the safety and efficacy of a programmed introduction of a sirolimus based calcineurin inhibitor free maintenance immunosuppressive regime three months after renal transplantation in recipients of a non-heart-beating donor kidney graft…
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
eGFR as determined by Nankivell at month 12 post randomization.
Secondary outcome
Biopsy proven acute rejection rate at month 12 post randomization
eGFR as determined by Cockroft Gault and MDRD methods at month 12 post
randomization
Suspected, treated and confirmed combined rejection rate
Graft survival
Patient survival
Rate of infection-viral,fungal,bacterial at 12 months post-randomisation
Rate of malignancy at 12 months post-randomisation
Dyslipidaemia at 3, 6 and12 months post-randomisation
Rate of proteinuria- mean increase in protein excretion by group and number of
patients, increasing protein excretion by > 0.5g/24hr and > 1g/24hr at 3, 6 and
12 months post-randomisation
Change in selectivity index of proteinuria at 3, 6 and 12 months
post-randomisation
Number of antihypertensive drugs at 3, 6 and 12 months post-randomisation
Rate of Serious Adverse Events at 12 months post-randomisation
Rate of treatment associated Adverse Events at 12 months post-randomisation
Rate of Cardiovascular events at 3 and12 months post-randomisation
Discontinuation rate at 6 and12 months post-randomisation
Mycophenolate area under the curve at randomisation
Background summary
Organ shortage requires extension of donor criteria, including accepting
non-heart-beating donors. To extend kidney graft half-life in this group
research into non-nephrotoxic immunosuppressive regimens is necessary. To date
most renal transplant centres prescribe a regimen combining calcineurin
inhibitor, inosine monophosphate inhibitor and corticosteroids. This is highly
efficacious in preventing acute rejection, but calcineurin inhibitors are
nephrotoxic. Introducing sirolimus three months after transplantation while
withdrawing the calcineurin inhibitor we expect to achieve a good control of
acute rejection, without increasing nephrotoxicity and impairing wound healing.
Study objective
To investigate the safety and efficacy of a programmed introduction of a
sirolimus based calcineurin inhibitor free maintenance immunosuppressive regime
three months after renal transplantation in recipients of a non-heart-beating
donor kidney graft on graft function and biopsy proven acute rejection rates.
Study design
Randomized, controlled, multi-center.
Intervention
At 3 months those recipients with an acceptable renal function will be
randomized to either continue on their calcineurin inhibitor based regime or
convert to sirolimus.
Study burden and risks
The burden associated with participation consists of weekly outpatient
department visits during the conversion period (from tacrolimus to sirolimus).
The amount and number of blood samples, physical examinations or other tests is
the same as in the control group: our standard care after renal
transplantation. The risks associated with the investigational product are
increase in proteinuria, dyslipidaemia, anaemia, thrombocytopenia, impaired
wound healing and development of lymphoceles.
Postbus 2040
3000 CA Rotterdam
Nederland
Postbus 2040
3000 CA Rotterdam
Nederland
Listed location countries
Age
Inclusion criteria
Age: at least 18 years
Acceptable renal function (eGFR Nankivell > 30 ml/min, proteinuria < 1.0 g/day)
3 - 4 months post renal transplantation with non-heart-beating donor graft
Exclusion criteria
Banff grade > 2 acute or vascular rejection at any time during this transplant pre-randomization
Multiple organ transplants (i.e., prior or concurrent transplantation of any organs other than renal transplant)..
Evidence of active systemic or localized major infection.
Planned use of agents with a known interaction with any of the following: sirolimus or its derivatives, macrolide antibiotics, corticosteroids, tacrolimus, or IMPDH inhibitor.
Immunosuppressive therapies other than those described above
Subjects with a screening/baseline total white blood cell count < 2,000/mm3 or ANC < 1000, platelet count < 100,000/mm3.
Fasting triglycerides > 400 mg/dL (> 4.5 mmol/L) or fasting total cholesterol > 300 mg/dL (> 7.8 mmol/L) despite optimal lipid-lowering therapy.
Subjects who are known to be HIV positive and/or subjects with active Hepatitis B or active Hepatitis C.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-002763-27-NL |
| CCMO | NL18145.078.07 |