| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Coronary Atheroma -- The current trial will study patients who have a clinical indication for coronary catheterization and who have coronary artery disease.
Ateroma coronario - este ensayo estudiará a pacientes con una indicación clínica de cateterización coronaria y con enfermedad arterial coronaria |
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| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to compare the effects of rosuvastatin 40mg with atorvastatin 80mg on the percent atheroma volume (PAV) of a coronary artery as measured by intravascular ultrasound (IVUS) imaging following 104 weeks of treatment in patients with coronary artery disease (CAD). |
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| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
1. To determine whether 104 weeks (24 months) of treatment with rosuvastatin 40mg or atorvastatin 80mg shows regression of PAV in the targeted coronary artery as measured by IVUS.
2. To compare the effects of rosuvastatin 40mg with atorvastatin 80mg on the total atheroma volume (TAV) in the targeted coronary artery as measured by IVUS.
3. To compare the effects of rosuvastatin 40mg with atorvastatin 80mg on lipid and lipoprotein metabolism.
4. To assess the safety and tolerability of rosuvastatin 40mg and atorvastatin 80mg during the 104 weeks of treatment in patients with CAD.
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Study of Coronary Atheroma by InTravascular Ultrasound: Effect of Rosuvastatin Versus AtorvastatiN (SATURN): A 104-week, randomized, double-blind, parallel group, multi-center Phase IIIb study comparing the effects of treatment with rosuvastatin 40mg or atorvastatin 80mg on atherosclerotic disease burden as measured by intravascular ultrasound in patients with coronary artery disease
Date and version of the sub-study: 05 October 2007, version 01
Objectives of this sub-study:
To obtain, with appropriate informed consent, DNA samples for future exploratory research on the effects of genetic polymorphisms on:
·Response to rosuvastatin or atorvastatin therapy
·Susceptibility to and prognosis of coronary heart disease (CHD) and lipid disorders
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| E.3 | Principal inclusion criteria |
1. Signed written informed consent to participate in the study.
2. Men or women 18 to 75 years of age.
3. Women must be non-lactating, not of childbearing potential (1 year post-menopausal or surgically sterilized [total hysterectomy, bilateral tubal ligation, bilateral oophorectomy]) or using a reliable method of birth control (eg, condoms with spermicide) considered suitable by the Investigator.
4. Clinical indication for coronary angiography.
5. Willing to follow all study procedures including adherence to lipid-lowering diet, study visits, fasting blood draws and compliance with study treatment regimen.
6. For patients with no statin therapy in the past 4 weeks: LDL-C levels > 100 mg/dL (2.6 mmol/L)
For patients on statin therapy in the past 4 weeks: LDL-C levels > 80 mg/dL (2.08 mmol/L)
7. Patients will be randomized to receive pre-treatment with either rosuvastatin 20 mg/d or atorvastatin 40 mg/d. All patients must attain LDL-C levels of <116 mg/dL (3.0 mmol/L) and triglyeride levels <500 mg/dL (5.65 mmol/L) at Visit 2, following 2 weeks of rosuvastatin 20 mg/d or atorvastatin 40 mg/d. This is to make it highly likely that all patients will achieve adequate LDL-C levels when randomized to either treatment arm, thus eliminating the need for rescue medication.
Angiographic Inclusion Criteria:
1. Entire coronary circulation: Must have angiographic evidence of CAD, as defined by at least 1 lesion in a native coronary artery that has >20% reduction in lumen diameter by angiographic visual estimation.
2. Left main coronary artery: Must have £50% reduction in lumen diameter by visual estimation.
3. Target Coronary Artery:
· Must be accessible to the IVUS catheter.
· Must have a < 50% reduction in lumen diameter by angiographic visual estimation throughout a target segment of at least 40 mm in length (the “target segment”). A lesion of up to 60% stenosis is permitted, distal to the target segment. A single branch of the “target vessel” may have a narrowing up to but < 70% by visual estimation as long as the target segment contains no lesion > 50%, and provided that the branch in question is not, and will not be, a target for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) during the course of the study.
· Has not sustained a myocardial infarction (MI).
· Has not undergone prior PCI or CABG surgery.
· The target vessel is not currently a candidate for intervention or a likely candidate for intervention over the next 24 months.
· The target vessel may not be a bypass graft.
· The target vessel may not be a bypassed vessel.
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| E.4 | Principal exclusion criteria |
1. Patients must not have been treated with the following lipid-lowering medications for more than 3 months in the past 12 months:
- rosuvastatin, any dose
- atorvastatin 40 or 80mg
- simvastatin 80mg
- Vytorin, any dose
- ezetimibe in combination with any statin
- Fibrates, any dose
- Niacin/nicotinic acid 250mg or more
- Omega III fatty acids 1000mg or more
Longer periods of treatment are not permitted because of the potential effects of such therapy on coronary atherosclerosis.
2. Patients who have symptoms consistent with moderate or greater severity of congestive heart failure (CHF) (New York Heart Association [NYHA] Class III or IV), or whose most recent determination of left ventricular ejection fraction (LVEF) is <0.35, by contrast left ventriculography, radionuclide ventriculography or echocardiography. The absence of an LVEF measurement does not prohibit entry into the study. Excluding patients with moderate or severe heart failure will avoid confounding the safety profile of statin therapy with possible non-drug-related cardiovascular events.
3. Clinically significant heart disease which, in the opinion of the Principal Investigator (or designee), is likely to require coronary bypass surgery, PCI, cardiac transplantation, surgical repair and/or replacement during the course of the study.
4. Uncontrolled hypertension at Visit 2, defined as either a resting diastolic blood pressure of ≥100 mmHg or a resting systolic blood pressure of ≥200 mmHg.
5. Known serious or hypersensitivity reactions to HMG-CoA reductase inhibitors.
6. Triglyceride (TG) level ≥500 mg/dL (5.65 mmol/L) at screening because patients with very high triglyceride levels warrant treatment with agents that may increase the risk of side effects associated with statin drugs.
7. Creatine kinase (CK) >3 times the upper limit of the normal (ULN) range at screening, because of the potential of statins to cause muscle abnormalities.
8. Known major hematologic, neoplastic, metabolic, gastrointestinal or endocrine dysfunction which, in the judgment of the Investigator, may affect the patient’s ability to complete the study.
9. History of malignancy, except in patients who have been disease-free >5 years or whose only malignancy has been basal or squamous cell skin carcinoma.
10. Life-threatening illness indicating the patient is not expected to survive for 104 weeks.
11. Unreliability as a study participant based on the Investigator’s knowledge of the patient, such as drug or alcohol abuse.
12. Participation in any investigational drug or device study within 30 days prior to study entry or expectation to participate in any other investigational drug or device study during the course of this study. Patients who withdraw from this study for any reason cannot re-enter the study.
13. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site).
14. Anticipated requirement of the use during the study of any medication listed in the Prohibited Medications Section (Table 3).
15. Uncontrolled diabetes, defined as glycosylated hemoglobin (HbA1C) ≥10% at screening.
16. Active liver disease or hepatic dysfunction, as determined by aspartate aminotransferase (AST [SGOT]), alanine aminotransferase (ALT [SGPT]) or bilirubin levels ≥1.5 x ULN at screening, because of the potential of statins to cause disturbances in liver function.
17. Secondary causes of hyperlipoproteinemia, such as uncontrolled primary hypothyroidism (defined as thyroid stimulating hormone [TSH] ≥1.5 x ULN), nephrotic syndrome, and/or renal dysfunction (serum creatinine ≥2.0 mg/dL [177 µmol/L]) at screening.
18. Coronary artery bypass surgery <6 weeks prior to the qualifying IVUS.
19. Significant medical or psychological condition that, in the opinion of the Investigator, would compromise the patient’s safety or successful participation in the study.
20. Baseline IVUS study determined to be of unacceptable quality by the IVUS core laboratory.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The nominal change (end of treatment minus pre-treatment) in percent atheroma volume (PAV) in a ≥ 40 mm segment of one targeted (imaged) coronary artery for all anatomically comparable slices (end of treatment and pre-treatment), as measured by IVUS. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 45 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| Last visit of the last subject. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
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