Plain English Summary
Background and study aims
Atherosclerosis is a chronic condition when the arteries are clogged with plaque. There can be many complications of this condition including heart attacks and strokes. Treatment with medications that help lower the cholesterol in the blood known as statins (such as rosuvastatin) are able to prevent cardiovascular events in both primary and secondary prevention mainly because of a significant reduction of cholesterol. A growing body of evidence suggests that statin could also have additional treatment impacts such as having anti-inflammatory effects. The aim of this study was aimed to investigate the effects of short-term treatment with usual dose or a higher dose of rosuvastatin, one of the most potent statins available, on mechanisms known for influencing the biology of atherosclerotic plaque.
Who can participate?
Adults aged 50 to 85 years old who are high-risk for cardiovascular disease.
What does the study involve?
Participants are randomly allocated to one or two groups. Those in the first group receive the lipid lowering treatment with rosuvastatin either at the usual dosage (10 mg/day). Those in the second group receive the lipid lowering treatment with rosuvastatin at a high dose (40 mg/day). The medication is administered once a day (at 8 p.m.), according to the drug indication, for 12 weeks in order to achieve a plasma level of LDL-cholesterol <100 mg/dL at the time of endarterectomy (e.g. after 12 weeks of treatment).Participants are followed up at 12 weeks with blood tests.
What are the possible benefits and risks of participating?
Participants may benefit from a reduction in their risk for cardiovascular disease. There are no major risks with participating.
Where is the study run from?
1. University of L'Aquila (Italy)
2. SS. Filippo e Nicola Hospital (Italy)
When is the study starting and how long is it expected to run for?
January 2009 to August 2011
Who is funding the study?
University of L'Aquila (Italy)
Who is the main contact?
Professor Giovambattista Desideri
Trial website
Contact information
Type
Scientific
Primary contact
Prof Giovambattista Desideri
ORCID ID
http://orcid.org/0000-0002-0145-1271
Contact details
Department of Life
Health and Environmental Sciences
University of L'Aquila
Coppito
L'Aquila
67100
Italy
Type
Scientific
Additional contact
Prof Francesco Cipollone
ORCID ID
Contact details
Regional Center for the Study of Atherosclerosis
Hypertension and Dyslipidemia
"SS Annunziata" Hospital
Ce.S.I.-Met
Geriatrics Clinic
Department of Medicine and Science of Aging
Chiety
66100
Italy
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
QUASAR
Study information
Scientific title
QUalitative Analysis of plaque Stability After Rosuvastatin therapy in asymptomatic patients enlisted to undergo carotid endarterectomy
Acronym
QUASAR
Study hypothesis
The aim of this study is to examine the effects of 2 different doses of rosuvastatin (10 and 40 mg/day) on mediator carotid plaque destabilization.
Ethics approval
Ethics Committee of the Public Health Agency of Avezzano-Sulmona, 06/15/2009, ref: protocol number 0040108/2019
Study design
Prospective single center randomised parallel group study
Primary study design
Interventional
Secondary study design
Randomised parallel trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Patients clinically asymptomatic patients enlisted to undergo elective carotid endarterectomy for reducing long-term risk of stroke
Intervention
Participants are randomly allocated to one or two groups. Those in the first group receive the lipid lowering treatment with rosuvastatin either at the usual dosage (10 mg/day). Those in the second group receive the lipid lowering treatment with rosuvastatin at a high dose (40 mg/day).
The medication is administered once a day (at 8 p.m.), according to the drug indication, for 12 weeks in order to achieve a plasma level of LDL-cholesterol <100 mg/dL at the time of endarterectomy (e.g. after 12 weeks of treatment). Although such a reduction was the minimum for keeping the patient, a higher reduction with rosuvastatin has been aimed at.
Participants are followed up at 12 weeks with blood tests.
Intervention type
Drug
Phase
Phase IV
Drug names
Rosuvastatin
Primary outcome measure
1. MicroRNA expression in atherosclerotic plaques is measured using pre-costumed
plates containing spotted microRNAs at week 12
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
3. RNA and/or protein levels of potential target of deregulated microRNAs were measured using the western blot analysis at week 12
Secondary outcome measures
1. Plasma total cholesterol was measured using the electrochemiluminescence technology at 12 weeks
2. Plasma low density lipoprotein (LDL) is measured using the electrochemiluminescence technology at 12 weeks
3. Plasma high density lipoprotein (HDL) was measured using the electrochemiluminescence technology at 12 weeks
4. Plasma triglycerides was measured using the electrochemiluminescence technology at 12 weeks
5. Plasma glucose was measured using the electrochemiluminescence technology at 12 weeks
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
Overall trial start date
10/01/2009
Overall trial end date
11/08/2011
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
70
Participant 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 [β-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
Recruitment start date
20/07/2009
Recruitment end date
15/12/2010
Locations
Countries of recruitment
Italy
Trial participating centre
University of L'Aquila
Geriatric Unit
Via G. Di Vittorio, s.n.c.
Avezzano
L'Aquila
67100
Italy
Trial participating centre
SS. Filippo e Nicola Hospital
Vascular Surgery Unit
Via G. di Vittorio
Avezzano
67051
Italy
Sponsor information
Organisation
University of L'Aquila
Sponsor details
Department of Life Health and Environmental Sciences
Coppito
L'Aquila
67100
Italy
Sponsor type
University/education
Website
Organisation
University of Chieti
Sponsor details
Regional Center for the Study of Atherosclerosis
Hypertension and Dyslipidemia
"SS Annunziata" Hospital
Ce.S.I.-Met
Geriatrics Clinic
Department of Medicine and Science of Aging
Chieti
66100
Italy
Sponsor type
Other
Website
Organisation
University of L'Aquila
Sponsor details
Sponsor type
Not defined
Website
Funders
Funder type
Not defined
Funder name
ASTRAZENECA S.p.A., Basiglio (MI), via Francesco Sforza, Palazzo Volta, CAP 20080, Italy
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Italian Ministry of University and Scientific Research (COFIN MIUR 2009, protocol number 2009L4X28T_002)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
The results of the study will be submitted for publication to a peer reviewed journal within the next few weeks.
IPD sharing statement:
The datasets generated during and/or analysed during the current study is not expected to be made available. The dataset is held in the database of study investigators but they are not available since participants were not previously requested to authorize the sharing of their clinical informations with other research groups other than those of study investigators
Intention to publish date
30/11/2018
Participant level data
Not expected to be available
Basic results (scientific)
Publication list