Objective: To investigate the safety and efficacy of a therapy consisting Everolimus and corticosteroids maintenance immunosuppressive regime twelve months after renal transplantation in recipients of donor kidney graft on graft function and acute…
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoints: Renal function. The percentage of patients that need
reconversion to their original therapy.
Secondary outcome
Secondary endpoints: Cardiovascular incidents and PWV/ AGES, Blood pressure and
the number of antihypertensives. The incidence of malignancies, the incidence
of infections, Haematological and Lipid parameters, Proteinuria.
Background summary
Rationale: Calcineurin inhibitor-free immunosuppression in kidney
transplantation give low rejection rates and excellent graft survival
nowadays1. Despite this success, mortality and morbidity in transplant
recipients is relatively high due to side effects of our immunosuppressive
strategies. This is one of the reasons for the high cardiovascular mortality in
renal transplant recipients. Calcineurin inhibitors may play an important role
in the development of chronic allograft nephropathy causing poor kidney
function and cardiovascular disease2,3. Also infections and malignancies are
the result of immunosuppression in general.
Drugs that might prevent atherosclerosis and malignancies have been developed
in the last decade: Everolimus is a promising agent that is known for reduced
rates of cytomegalovirus (CMV) infection and of cardiac allograft
vasculopathy4. It also carries the promise in a reduced risk for developing
cancer.5 By introducing Everolimus twelve months after transplantation while
withdrawing the calcineurin inhibitor and the inosine monophosphate inhibitor
we expect to achieve a good control of acute rejection, without increasing
nephrotoxicity. In a previous study (not published yet) we introduced
Everolimus in a dosage of 3 mg two times a day, six months post
transplantation. Probably due to that high dose more side effects were seen
than expected.
In this present study we will optimize the dose of Everolimus.
Study objective
Objective: To investigate the safety and efficacy of a therapy consisting
Everolimus and
corticosteroids maintenance immunosuppressive regime twelve months after renal
transplantation
in recipients of donor kidney graft on graft function and acute rejection
rates. The other group will
receive a low-dose regimen consisting a low-dose calcineurin inhibitor, low
dose MMF and
corticosteroids.
Study design
Study design: Prospective, open, randomized, controlled, single-centre.
Intervention
Intervention: At twelve months those recipients with an acceptable renal
function will be randomized to either continue on their calcineurin inhibitor
based regime in a lower dose, or convert to Everolimus.
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness:
The burden associated with participation consists of more frequently outpatient
visits during the conversion period. 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. The benefits associated with
Everolimus are reduced rates of cytomegalovirus (CMV) infection and of cardiac
allograft vasculopathy, together with a decreased risk for cardiovascular
diseases and malignancies in the long term survival.
Hanzeplein 1
9700 RB Groningen
Nederland
Hanzeplein 1
9700 RB Groningen
Nederland
Listed location countries
Age
Inclusion criteria
• Female or male, aged between 18 and 70 years.
• Recipient of a kidney graft from a deceased donor or living (non-HLA identical) donor.
• The patient understands the purpose and risks of the study and has given written informed consent to participate in the study.
• Acceptable renal function, eGFR > 40 ml/min, Proteinuria <= 1, 0 g/24hr.
Exclusion criteria
• Patients with multi-organ transplants.
• Patients who have been receiving a second or subsequent transplant.
• Patients with very low function at 1 year post-transplant, GFR < 40.
• Proteinuria > 1, 0 g/24 hr.
• Patients with a screening/baseline total white blood cell count < 2,0 10Eg/l or ANC < 1,0 10Eg/l, platelet count < 100 10Eg/l.
• Patients with baseline fasting triglycerides > 4.5 mmol/l or fasting total cholesterol > 7.8 mmol/l despite optimal lipid-lowering therapy.
• Presence of sub clinical rejection (Borderline or Banff score >1a) in biopsy taken at approximately month 12
• Vascular or Acute rejection (Banff score >= 2a) six months preceding randomization.
• Female patients who are pregnant or unwilling to use adequate contraception during the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-014436-38-NL |
| CCMO | NL29025.042.09 |