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Cardiovascular Medicine - Active Clinical Trials
SATURN


Primary Investigator: Richard Webel, MD

Study Coordinator: Kathy Belew, CNS-BC

Status: Closed to enrollment; follow-up continues

Study Title: 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 40 mg or Atorvastatin 80 mg on atherosclerotic disease burden as measured by intravascular ultrasound in patients with coronary artery disease (CAD).

Purpose: The primary objective of this study is to compare the effects of rosuvastatin 40 mg with atorvastatin 80 mg 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 CAD.

Inclusion Criteria:
For inclusion in the study patients must satisfy all the following criteria:
1. Men or women 18 to 75 years of age.
2
. Women must be non-lactating, not of childbearing potential (one-year postmenopausal or surgically sterilized [total hysterectomy, bilateral tubal ligation, bilateral oophorectomy]) or using a reliable method of birth control (e.g., condoms with spermicide) considered suitable by the investigator.
3. Clinical indication for coronary angiography.
4
. Willing to follow all study procedures including adherence to lipid-lowering diet, study visits, fasting blood draws and compliance with study treatment regimen.
5
. For patients with no statin therapy in the past four weeks: LDL-C levels > 100 mg/dL (2.6 mmol/L)
   
For patients on statin therapy in the past four weeks: LDL-C levels > 80 mg/dL (2.08 mmol/L)
6. 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 two 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 one 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.
      ••   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.

Exclusion Criteria:
Any of the following is regarded as a criterion for exclusion from the study:
1. Patients must not have been treated with the following lipid-lowering medications for more than three months in the past 12 months:
- Rosuvastatin, any dose
- Atorvastatin 40 or 80 mg
- Simvastatin 80 mg
- Vytorin, any dose
- Ezetimibe in combination with any statin
- Fibrates, any dose
- Niacin/nicotinic acid 250 mg or more
- Omega III fatty acids 1000 mg 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.
- Ezetimibe in combination with any statin
- Fibrates, any dose
- Niacin/nicotinic acid 250 mg or more
- Omega III fatty acids 1000 mg or more
Longer periods of treatment are not permitted because of the potential effects of such therapy on coronary atherosclerosis.
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
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.

Restrictions:
The following restrictions will be applied to patients in this study:
1. Patients who are blood donors should not donate blood during the study, and for one month following their last dose of study treatment.
2. Patients will fast (water is permitted) and refrain from alcohol consumption for at least eight hours before each visit in which lipids are to be assessed.
3. Patients will refrain from cigarette smoking at least 12 hours before each visit in which lipids are to be assessed.
4. Patients will be advised to maintain their normal physical activities or exercise routines during the study.
5. Patients will be counselled to avoid starting cholesterol-lowering food supplements or restricted medications while participating in this study. Investigators should use their discretion to determine whether other medications or supplements qualify as cholesterol-lowering therapies.

Actions:
••  Call Kathy Belew (beeper: 573-499-8063) and/or on-call research nurse (on-call beeper 573-499-8084) or Dr. Webel for notification if subject is admitted to the hospital or for questions regarding medication.




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