Clinical trial NCT01524601: The Rosuvastatin In TrAnsplant Recipients Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Disorder Related to Renal Transplantation
Hypercholesterolemia
Keywords: Immunosuppression
Everolimus
rosuvastatin
fluvastatin
Lipid lowering
Lead sponsor: University of Oslo School of Pharmacy
Sponsor class: OTHER
Collaborators: name: Oslo University Hospital
First posted: 2012-02-02
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: compare the treatment efficacy (blood lipid lowering effect) of rosuvastatin versus fluvastatin
timeFrame: 4 weeks
measure: 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.
timeFrame: 4 weeks
Secondary outcomes:
measure: 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.
timeFrame: 4 weeks
measure: 2. Investigate P-gp activity in whole blood in everolimus treated patients
timeFrame: 4 weeks
measure: 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
timeFrame: 4 weeks
measure: 4. Compare effect of rosuvastatin versus fluvastatin therapy on the renal function (eGFR)
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital, Rikshospitalet
Study officials:
affiliation: University of Oslo
name: Anders Åsberg, PhD
role: STUDY_DIRECTOR
References:
citation: Robertsen I, Asberg A, Granseth T, Vethe NT, Akhlaghi F, Ghareeb M, Molden E, Reier-Nilsen M, Holdaas H, Midtvedt K. More potent lipid-lowering effect by rosuvastatin compared with fluvastatin in everolimus-treated renal transplant recipients. Transplantation. 2014 Jun 27;97(12):1266-71. doi: 10.1097/01.TP.0000443225.66960.7e.