The Rosuvastatin In TrAnsplant Recipients Study

Study Overview
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Brief Summary
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Renal transplant recipients need life long immunosuppression and one of the new drugs is everolimus. Everolimus is a potent immunosuppressive drug and one of the main side-effects are increased blood cholesterol levels. Many renal transplant recipients are treated with a cholesterol lowering agent, mainly fluvastatin. Rosuvastatin is a new cholesterol lowering drug on the market with a potential higher cholesterol lowering potency. In the present study the investigators will examine the hypothesis that rosuvastatin reduce cholesterol levels more than fluvastatin in renal transplant patients.

Official Title
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The RITA-study -- An Open Study to Evaluate the Blood Lipid Lowering Effect of Rosuvastatin Versus Fluvastatin and the Bilateral Interaction Between Everolimus and Rosuvastatin in Renal Transplant Recipients

Conditions
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Disorder Related to Renal Transplantation, Hypercholesterolemia

Intervention / Treatment
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* Drug: Rosuvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal transplant recipients with stable renal function (plasma creatinine < 200 µmol/L) Renal transplant recipients on an everolimus and fluvastatin based therapy for minimum 3 months prior to inclusion > 18 years of age Male patient or female patient without childbearing potential (surgically sterilized or postmenopausal) or if female of childbearing potential; is not lactating, has a negative pregnancy test at screening and is willing to utilize an effective method of contraception throughout the study period and for 90 days following discontinuation of the study drugs Signed informed consent Exclusion Criteria: Patients experiencing an acute rejection episode within 2 weeks before or after inclusion, whether proven by biopsy or not Patients with a known hypersensitivity to rosuvastatin Change in enzyme inducing or inhibiting drugs within the last 2 weeks prior to and throughout the study [e.g. barbiturates, rifampicin, ketoconazole, erythromycin, cimetidine and similar drugs] Pregnant or nursing mothers

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rosuvastatin<br>Rosuvastatin treatment for 4 weeks | Drug: Rosuvastatin<br>* 20 mg rosuvastatin for 4 weeks<br>* Other names: Crestor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| compare the treatment efficacy (blood lipid lowering effect) of rosuvastatin versus fluvastatin | Compare the blood lipid levels before and after switch from fluvastatin to rosuvastatin | 4 weeks | 
| Area Under Curve (AUC) of rosuvastatin in renal transplant recipients treated with everolimus. Time frame: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post dose. | Compare 24-h pharmacokinetics of renal transplant recipients with historic controls | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Area Under Curve (AUC) of everolimus during rosuvastatin versus fluvastatin therapy, including intracellular everolimus concentrations within T-lymphocytes. Time frame: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours post-dose. |  | 4 weeks | 
| 2. Investigate P-gp activity in whole blood in everolimus treated patients |  | 4 weeks | 
| 3. Study inter individual variation in rosuvastatin and everolimus pharmacokinetics in renal transplant recipients due to polymorphism in the genes encoding P-gp, OATP1B1 and CYP3A5 |  | 4 weeks | 
| 4. Compare effect of rosuvastatin versus fluvastatin therapy on the renal function (eGFR) |  | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunosuppression, Everolimus, rosuvastatin, fluvastatin, Lipid lowering