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

Rheumatoid Arthritis Clinical Trial

— RORAAS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01389388
• Other study ID #: 2009/2219
• Secondary ID: 2008-005551-20
• Status: Completed
• Phase: N/A
• First received: April 16, 2010
• Last updated: May 6, 2015
• Start date: January 2013
• Est. completion date: August 2013

Study information

• Verified date: May 2015
• Source: Diakonhjemmet Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 80 Years

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Ankylosing Spondylitis
• Arthritis
• Arthritis, Rheumatoid
• Carotid Artery Plaque
• Carotid Stenosis
• Joint Diseases
• Rheumatoid Arthritis
• Spondylitis
• Spondylitis, Ankylosing

Intervention

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.

Locations

Country	Name	City	State
Norway	Anne Grete Semb, Department of Rheumatology, Diakonhjemmet hospital	Oslo

Sponsors (1)

Lead Sponsor	Collaborator
Diakonhjemmet Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Carotid artery cholesterol plaque regression and stabilization	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	Yes
Secondary	Disease activity and health measures, lipoprotein components and inflammatory biomarkers	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	Yes
Secondary	Carotid artery cholesterol plaque regression and stabilization	Lipoprotein components: Lipids, apolipoproteins, magnitude and functional measurements of these, for example of HDL	18 months	Yes
Secondary	Carotid artery cholesterol plaque regression and stabilization	Biomarkers/inflammation parameters	18 months	Yes