In this study the IMP, rosuvastatin, is used as a tool compound for creating favourable lipid-altering, anti-inflammatory or other pleiotropic effects which are believed to change coronary flow reserve (CFR).
Conditions
Interventions
Trade Name: Crestor
Product Name: rosuvastatin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: rosuvastatin
Other descriptive name: rosuvastatin calcium
Concentration unit: mg milligram(s
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males aged 45-75 years or females aged 60-75 years inclusive 2. Carotid and/or femoral atherosclerotic plaque(s), defined as a distinct area with an intima media thickness (IMT) >50% thicker than that of neighbouring sites (visually judged), as previously assessed by carotid ultrasound examination within the last 5 years 3. Dyslipidaemia: Apolipoprotein (Apo)B/A1 ratio >0.60 4. Provision of signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Treatment with statins or other lipid-lowering drugs, e.g. fibrates, nicotinic acid, cholesterol absorption inhibitor, within the last 6 months before randomisation 2. Treatment with Persantin® or Asasantin® or other dypyridamole-like drugs 3. Treatment with glitazones or other peroxisome proliferator-activated receptors (PPAR) a/? agonists, metformin or insulin within the last 6 months 4. Known hypersensitivity to statins, adenosine or mannitol 5. Haemoglobin A1c (HbA1c) >7.5 % (Swedish standard) or random glucose >15 mmol/L at Enrolment visit 6. Initiation, cessation or dose change in any anti-diabetic medication within the last 3 months before randomisation 7. Initiation, cessation or dose change in any treatment with beta-blockers, Angiotensin-Converting Enzyme inhibitors (ACEi) or Angiotensin receptor blockers (ARBs) within the last 3 months before randomisation 8. Uncontrolled hypertension according to the investigator 9. Current smoking or snuff tobacco use 10. Major CV event (myocardial infarction (MI), stroke/ transitory ischemic attack (TIA), Acute Coronary Syndrome (ACS), revascularisation) within the last 6 months before randomisation 11. Symptomatic carotid stenosis, atrioventricular (AV) block, QT-prolongation, atrial fibrillation, sinus node disease (such as sick sinus syndrome or symptomatic bradycardia), chronic obstructive pulmonary disease (COPD) or asthma 12. History of myopathy, alcohol or drug abuse, epilepsy or seizures 13. A calculated creatinine-clearance corresponding to a GFR 3 x upper limit of normal (ULN), liver transaminases > 1.5 x ULN or anaemia 14. Hypothyroidism, in terms of a thyroid stimulating hormone (TSH) = 1.5 x ULN (patients with diagnosed hypothyroidism on replacement therapy are allowed provided they do not meet this TSH criterion) 15. Asian ethnicity, treatment with Vitamin K antagonists, protease inhibitors, rifampicine, cyclosporine or high-dose treatment with macrolide antibiotics 16. Malignant disease (except in patients who have been disease-free >5 years or whose only malignancy has been basal or squamous cell skin carcinoma), kidney disease, hepatic disease or inflammatory bowel disease 17. Systemic inflammatory disease or use of systemic corticosteroid treatment 18. Positive screen for Serum Hepatitis B Surface Antigen, Hepatitis C Antibodies and human immunodeficiency virus (HIV) 19. Donation of blood or plasma in any amount during the month prior to baseline visit or in excess of 170 mL during the 3 months prior to study start. 20. Previous bone marrow transplant (excludes only participation in the genetic sampling) 21. Whole blood transfusion within 120 days of the date of genetic sample collection 22. Intake of any investigational product within the last month before enrolment 23. Any other condition prohibiting study participation at the discretion of the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: · To evaluate the change after 1 month statin treatment in transthoracic Doppler echocardiography-coronary flow reserve (TTDE-CFR) peak velocity compared to baseline within the rosuvastatin 40 mg group · To evaluate the difference in treatment effects on CFR peak velocities after 1 month between the rosuvastatin group and the placebo group in favour of the rosuvastatin group ;Secondary Objective: • Changes in CFR peak velocity within the rosuvastatin group after 3 months compared to baseline and to 1 month • Changes in other CFR parameters after 1 month rosuvastatin treatment or placebo; comparisons within groups and between groups, respectively • Changes in plasma lipids, lipoproteins and other cardiovascular biomarkers after 1 month of treatment with rosuvastatin or placebo; comparisons within groups and between groups, respectively • Rosuvastatin treated group only: changes within group in plasma lipids, lipoproteins and other cardiovascular biomarkers after 3 months of treatment with rosuvastatin compared to baseline and to 1 month, respectively • Explore relationships between CFR and plasma biomarkers, also after consideration of baseline characteristics of the subjects • To receive information on the variability of included variables • To collect and store DNA for future exploratory research into genes related to atherosclerotic and cardiovascular disease;Primary end point(s): The main purpose of this study is to evaluate the usefulness of Transthoracic Doppler Echocardiography (TTDE) to assess coronary flow reserve (CFR) and how it can be utilized as a composite biomarker for coronary artery function. Ultimately, the method may be used for monitoring drug effects in patients with increased cardiovascular risks. | — |
Countries
Sweden
Outcome results
None listed