Effects of Rosuvastatin on Carotid Artery Plaques in Patients With Inflammatory Joint Disease (RORAAS)

May 6, 2015 updated by: Anne Grete Semb, Diakonhjemmet Hospital

Cholesterol Plaques in Carotid and Coronary Arteries and the Effect of Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases

Patients with rheumatoid Arthritis (RA) and Ankylosing Spondylitis (AS) are at greater risk of developing cardiovascular disease. The reason(s) for this have not been well investigated, but there is a general understanding that systemic inflammation plays a part in the increased cardiovascular morbidity and mortality. In spite of the increased risk in these patients, they have not been included as a high risk patient group in cardiovascular prevention guidelines.

The investigators have carried out a cardiovascular study of RA and AS patients, as well as patients with arthritis for the first time. The investigators have demonstrated cholesterol plaques in the carotid artery in some of these patients. Plaques in the carotid artery represent a risk for development of cerebral stroke and are significantly associated with myocardial infarction. These plaques, which are asymptomatic and do not cause haemodynamically significant narrowing, diameter reduction (i.e. operation is not indicated), are vascular atheromatous disease. Therefore, according to prevailing cardiovascular guidelines (SCORE 2007), these patients shall have secondary prevention with a lipid lowering agent with the LDL-cholesterol goal of 1.8 mmol/L and HDL-cholesterol > 1.0 mmol/L for men and > 1.1 mmol/L for women.

Statins are cholesterol-lowering drugs, and have been shown to reduce the risk of cardiovascular disease significantly. In addition, reduction in the size of coronary plaques has been induced by statins, when the LDL has been reduced to 1.6-1.8 mmol/l. Plaques in the carotid or coronary arteries have not previously been treated and characterized in patients with RA, AS and other inflammatory forms of arthritis.

The aim of this study is to treat patients with cholesterol plaques in the carotid artery with cholesterol-lowering medication, in the form of Rosuvastatin for 18 months, and characterize the effects on the plaques in the carotid and coronary arteries. In addition, the investigators want to clarify the connection between plaques in the carotid and coronary arteries in patients with RA, AS and other inflammatory forms of arthritis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

114

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Norway
      • Oslo, Norway, NO-0319
        • Anne Grete Semb, Department of Rheumatology, Diakonhjemmet hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

31 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Women and men with RA, AS and other inflammatory forms of arthritis, aged 35-80 years.
  2. Cholesterol plaques demonstrated in carotid artery by ultrasound.
  3. Informed consent.

Exclusion Criteria:

  1. Concomitant statin treatment
  2. Arterial fibrillation or others with chronic irregular heart rhythm (because of CT).

  3. Contraindication to statin treatment.

    • Hypersensitivity to statins
    • Liver disease with ASAT/ALAT ≥ twice the upper normal limit
    • Previous statin-induced myopathy or severe hypersensitivity reactions to other statins
    • Raised creatinine (because of contrast medium)
    • Pregnancy or breast feeding
    • Fertile women who do not use contraceptives
    • Cyclosporine treatment
    • Treatment with medicinal products that have a known interaction with Rosuvastatin
    • Uncontrolled hypothyroidism defined as TSH > 1.5 times ULN at the first visit (because of the connection between myopathy and hypothyroidism with statin treatment)
    • Creatinine clearance < 30 ml/min and <60 ml/min with a Rosuvastatin dose of 40 mg per day

  4. Secondary hyperlipidemia

    • Primary hyperthyroidism
    • Nephrotic syndrome, creatinine > 2 mg/dl
    • Uncontrolled diabetes mellitus (HbA1C > 10 %)
    • Plasma Triglycerides > 6.8 mmol/l

  5. Other diseases or treatment that reduces the safety, or treatment with Rosuvastatin which would interfere with the end points of the study

    • Heart failure: NYHA class III B/IV
    • Haemodynamically significant valve defects
    • Established statin treatment
    • Gastrointestinal disease/treatment that can give malabsorption of Rosuvastatin
    • Cancer
    • Severe psychiatric disease
    • Life-threatening ventricular arrhythmias
    • Other medication that increases the risk of rhabdomyolysis
    • Known abuse of alcohol
    • Participation in other studies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rosuvastatin intervention
Patients > 70 years will be given Rosuvastatin of 5 mg a day, uptitering the dose until the LDL level of 1.6-1.8 mmol/l has been reached. Patient <70 years, strat on Rosuvastatin 20 mg a day, uptitered to 40 mg a day, with the LDL of 1.6-1.8 mmol/l. -1.8 mmol/l. The objective is that all the participants should have reached a LDL level of 1.6-1.8 mmol/l 3 months after the start of the study. The participants will remain on Rosuvastatin medication for a total of 18 months.
Drug: Rosuvastatin
All the patients who have signed the informed consent will after they have had performed a MCT and possibly SCC with an IVUS, will be give Rosuvastatinuntill their LDL level has reached 1.6-1.8 mmol/l. The objective is that all the participants should have reached 1.6-1.8 mmol/l 3 months after the start of the study. The participants will remain on Rosuvastatin medication for a total of 18 months.
Other Names:
  • Brand name for Rosuvastatin is Crestor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Carotid artery cholesterol plaque regression and stabilization
Time Frame: 18 months
Reduction of plaque area and change of the plaque morphology to less vulnerable for rupture after 18 months with 40 mg Rosuvastatin daily.
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease activity and health measures, lipoprotein components and inflammatory biomarkers
Time Frame: 18 months
Disease activity and Health status i. Disease activity will be measured by: 28-swollen-joint count, AIMS2, BASDAI ii. Health status will be measured by MHAQ, BASFI, Pain VAS, Fatigue VAS, life quality (HRQoL)
18 months
Carotid artery cholesterol plaque regression and stabilization
Time Frame: 18 months
Lipoprotein components: Lipids, apolipoproteins, magnitude and functional measurements of these, for example of HDL
18 months
Carotid artery cholesterol plaque regression and stabilization
Time Frame: 18 months
Biomarkers/inflammation parameters
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Diakonhjemmet Hospital

Investigators

  • Principal Investigator: Anne G Semb, MD, PhD, Diakonhjemmet Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

August 1, 2013

Study Completion (Actual)

August 1, 2013

Study Registration Dates

First Submitted

April 16, 2010

First Submitted That Met QC Criteria

July 7, 2011

First Posted (Estimate)

July 8, 2011

Study Record Updates

Last Update Posted (Estimate)

May 7, 2015

Last Update Submitted That Met QC Criteria

May 6, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2009/2219
  • 2008-005551-20 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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