Study on the effects of rosuvastatin therapy on carotid plaque composition in asymptomatic patients enlisted to undergo carotid endarterectomy

Phase 4

Completed

• Conditions: Stroke; Patients clinically asymptomatic patients enlisted to undergo elective carotid endarterectomy for reducing long-term risk of stroke; Nervous System Diseases

• Registration Number: ISRCTN16590640
• Lead Sponsor: niversity of L'Aquila

Brief Summary

2020 results in https://pubmed.ncbi.nlm.nih.gov/31409515/ (added 25/11/2020)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2011-08-11
• Study Start: 2017-10-03
• Last Update Posted: 7 December 2020

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Clinical indication to the endarterectomy according to the international guidelines
2. Male or female patients between the ages of 50 and 85 years
3. LDL-cholesterol >100 mg/dl
4. Extracranial high-grade internal carotid artery (ICA) stenosis, near to carotid bifurcation
5. Patients have to be clinically stable at the time of randomization
6. High-risk patients, as defined by one or more of the following criteria:
6.1. Prior history > 4 weeks of cerebrovascular accident (CVA) or transient ischemic attack (TIA) consistent with North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria or prior history of amaurosis fugax occurring at any time.
6.2. Baseline hsCRP >2 mg/L
6.3. Echolucent plaque [Grey Scale Median (GSM) <25] on carotid ultrasound

Exclusion Criteria

1. Chronic treatment with lipid-lowering agents including bile acid sequestrants, HMG-CoA-reductase inhibitors and nicotinic acid taken within 6 weeks and fibrates taken within 8 weeks of randomization, and probucol taken within 1 year of randomisation
2. History of statin induced myopathy, or serious hypersensitivity reaction to other HMG-CoA reductase inhibitors (statins) including rosuvastatin
3. Participation in another investigational drug study less than 4 weeks before enrolment in the study, or according to subjects local ethics committee requirements where a larger period is stipulated
4. Serum creatinine >176 mmol/L (2.0 mg/dL) or alternative threshold appropriate to study, to comply with label
5. Unexplained creatine kinase (CK 3xULN)
6. Current active liver disease (ALT/SGPT >2xULN) or severe hepatic impairment
7. History of alcohol or drug abuse within the last 5 years
8. Uncontrolled hypothyroidism defined as a thyroid stimulating hormone (TSH)>1.5 xULN
9. Nephrotic syndrome, anorexia nervosa or any other cause of secondary hyperlipidemia
10. History of malignancy (unless a documented disease free period exceeding 5-years is present) with the exception of basal cell or squamous cell carcinoma of the skin
11. Pregnant women, women who are breast feeding, and women of childbearing potential who are not using chemical or mechanical contraception or have a positive serum pregnancy test (a serum b-human chorionic gonadotrophin [ß-HCG] analysis)
12. Patients on systemic immunosuppressive drugs including cyclosporine; systemic antifungal agents of the azole class including itraconazole and ketokonazole; erythromicin or clarithromycin; nefazodone; chronic systemic glucocorticoid therapy, or protease inhibitors
13. Partial ileal bypass
14. Any other condition or therapy, which, in the opinion of the investigator, might pose a risk to the patient or confound the results of the study
15. Poor mental function or any other reason to expect patient difficulty in complying with the requirements of the study
16. Treatment with any other investigational drug within 30 days prior to Visit 1
17. Patients not competent to give informed consent because of receptive language difficulty, intellectual decline, or psychiatric illness
18. Patients without clear and adequate selective angiographic visualization of the carotid arteries or their intracranial branches
19. Patients with carotid occlusive disease distal to the body of the second cervical vertebral body that is more significant than the surgically accessible lesion in the more prossimal portion of the artery
20. Patients with total internal carotid artery occlusion or carotid stenosis of less than 60%
21. Patients with previous cerebral infarction on either side of sufficient size to deprive the patient of all useful function in the affected territory
22. Patients who had a previous ipsilateral carotid endarterectomy

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> 1. MicroRNA expression in atherosclerotic plaques is measured using pre-costumed<br> plates containing spotted microRNAs at week 12<br> 2. RNA and/or protein levels of metalloproteinases, cholesterol transporters and other mediators of plaque destabilization in atherosclerotic plaques are measured using the western blot analysis at week 12<br> 3. RNA and/or protein levels of potential target of deregulated microRNAs were measured using the western blot analysis at week 12<br>

Secondary Outcome Measures

Name	Time	Method
<br> 1. Plasma total cholesterol was measured using the electrochemiluminescence technology at 12 weeks<br> 2. Plasma low density lipoprotein (LDL) is measured using the electrochemiluminescence technology at 12 weeks<br> 3. Plasma high density lipoprotein (HDL) was measured using the electrochemiluminescence technology at 12 weeks<br> 4. Plasma triglycerides was measured using the electrochemiluminescence technology at 12 weeks<br> 5. Plasma glucose was measured using the electrochemiluminescence technology at 12 weeks<br> 6. Plasma markers of inflammation such as CRP, sVCAM-1, sICAM-1, soluble E-selectin, soluble P-selectin were measured using enzyme immunoassay at 12 weeks<br>