Individually Adapted Immunosuppression in de Novo Renal Transplantation Based on Immune Function Monitoring: a Prospective Randomised Study

Study Overview
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Brief Summary
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This study is an open, randomised trial in which one group of patients (control) will receive the golden standard therapy and the other group (treatment) will receive individually adapted immunosuppression.

Official Title
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Individually Adapted Immunosuppression in de Novo Renal Transplantation Based on Immune Function Monitoring: a Prospective Randomised Study

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: individual adapted immunosuppression
* Drug: golden standard therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First or second kidney transplantation Males and females, 18 years old or older Women of childbearing potential must have a negative serum or urine pregnancy test with sensitivity equal to at least 50 mIU/mL Patients must be capable of understanding the purpose and risks of the study and must sign an informed consent form Exclusion Criteria: Multiple organ transplantation (eg. kidney-pancreas, kidney-heart, kidney-liver,...) Transplantation of a patient who received another organ transplant previously except one kidney transplant Recipients of HLA-identical living-related renal transplants Patients with PRA > 10%, patients who have lost a first graft from rejection. Pregnant or lactating women WBC =< 2.5 x 109/L (IU), platelet count =< 100 x 109/L (IU), or Hb =< 6g/dl at the time of entry into the study Active peptic ulcer Severe diarrhea or other gastrointestinal disorders which might interfere with the ability to absorb oral medication, including diabetic patients with previously diagnosed diabetic gastroenteropathy Known HIV-1 or HTLV-1 positive tests History of malignancy in the past 5 years (with the exception of adequately treated basal or squamous skin cell carcinoma) The use of investigational drugs or other immunosuppressive drugs as those specified in this protocol Patients receiving bile acid sequestrants Psychological illness or condition interfering with the patient's compliance or ability to understand the requirements of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>individual adapted immunosuppression | Drug: individual adapted immunosuppression<br>* individual adapted immunosuppression<br>|
| Active Comparator: 2<br>golden standard therapy | Drug: golden standard therapy<br>* golden standard therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft function as measured by Cr EDTA AUC |  | at 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft survival |  | at 1 year | 
| Patient survival |  | at 1 year | 
| Graft function measured by estimated GFR (eGFR) (MDRD and Cockroft-Gault) |  | at 1 year | 
| Frequency of biopsy proven acute rejection episodes |  | at 1 year | 
| Incidence of biopsy proven acute rejection (BPAR) and clinical (non-biopsy proven) acute rejection episodes treated by a full course anti-rejection therapy (e.g. steroids) (Treatment of rejection according to center practice). |  | at 1 year | 
| Incidence of rejection treated by antibodies (OKT3, ATG) |  | at 1 year | 
| Time to first rejection (days) |  | at 1 year | 
| Severity of rejection as assessed by BANFF 2005 score |  | at 1 year | 
| Number of acute rejections per patient |  | at 1 year | 
| Plasma creatinine and eGFR |  | at month 1, 3 and yearly (2 and 3 years) | 
| Measured GFR |  | at month 3 and yearly | 
| Proteinuria |  | at month 1, 3 and at 1 and 3 years | 
| Incidence and score of borderline changes and acute rejection |  | in month 3 and month 12 biopsy | 
| Incidence and score of chronic alloimmune injury/rejection and nonimmune injury |  | in month 3 and month 12 biopsies (BANFF 2005) | 
| Development and evolution of glucose abnormalities |  | at 1 year | 
| blood pressure |  | at 1 year | 
| ambulatory 24-hr blood pressure monitoring |  | at 1 year and 3 years | 
| Left ventricular mass assessed by echocardiography |  | at 1 year and 3 years | 
| Fasting lipid profile |  | at baseline, month 1,3,6 and yearly | 
| CMV infection (as measured with whole blood PCR) and disease |  | at 1 year | 
| Polyoma virus replication as measured by whole blood PCR |  | at 1 year | 
| Incidence of BK nephritis |  | in month 3 and month 12 biopsies | 
| Incidence of PTLD and Nonmelanoma skin cancer |  | at 1 year and yearly | 
| Incidence of EBV reactivation (as measured with whole blood PCR) |  | at 1 year and yearly |