The Rosuvastatin In TrAnsplant Recipients Study (RITA)

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

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia; Disorder Related to Renal Transplantation
• Intervention / Treatment: Drug: Rosuvastatin

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0027
    • Oslo University Hospital, Rikshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin; Rosuvastatin treatment for 4 weeks	Drug: Rosuvastatin; 20 mg rosuvastatin for 4 weeks; Other Names: Crestor

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: University of Oslo School of Pharmacy
• Collaborators: Oslo University Hospital
• Investigators: Study Director: Anders Åsberg, PhD, University of Oslo

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: January 24, 2012
• First Submitted That Met QC Criteria: February 1, 2012
• First Posted (Estimate): February 2, 2012

Study Record Updates

• Last Update Posted (Estimate): October 12, 2012
• Last Update Submitted That Met QC Criteria: October 11, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Immunosuppression; Everolimus; rosuvastatin; fluvastatin; Lipid lowering
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: RITA-11