| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Men or women who are >18 and <75 years old diagnosed with non ST elevation - acute coronary syndrome (NSTE-ACS) and onset of clinical symptoms less than 24 hours at the admission for which a PCI is planned or anticipated. Patients with STEMI and primary PCI planned within 24 hours of admission will not be included. Patients will not be allowed to have taken any cholesterol-lowering medications during 1 month prior to enrolment. |
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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 |
| to compare the efficacy of rosuvastatin 20 mg versus atorvastatin 80 mg in reducing ApoB/ApoA-I ratio at 3 months in acute coronary syndrome (ACS) patients receiving the study treatment after a PCI. |
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| E.2.2 | Secondary objectives of the trial |
to assess in ACS patients:
1.The efficacy of rosuvastatin 20 mg versus atorvastatin 80 mg in reducing the LDL-C level at 1 month and 3 months in patients receiving the study treatment after a PCI
2.The efficacy of early started rosuvastatin 20 mg versus placebo on hs-CRP from the admission of patients (Day –6) until start of study treatment after the PCI (Day 0).
3.The efficacy of rosuvastatin 20 mg versus atorvastatin 80 mg in reducing ApoB/ApoA-I ratio at 1 month in patients receiving the study treatment after a PCI.
The groups not formally compared will be summarised descriptively.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
This is a study of non-STE patients with ACS admitted to hospital within 24 hours of symptoms onset who will be scheduled for a Percutaneous Coronary Intervention (PCI) for treatment of the index event according to the local or European Guidelines for PCI (Silber S. 2005). Non-STE ACS patients include those with unstable angina and non-STE MI (Cannon et al 2001). See Appendix G.
For inclusion into the randomised treatment phase of the study, patients must fulfil all of the following criteria:
1. Provision of written informed consent.
2. Men or women who are ³ 18 and £ 75 years old.
3. Hospital admission for ACS with chest pain or discomfort occurring during rest or with minimal exertion, relieved by nitroglycerin or lasting for at least 15 minutes if untreated, and with the most recent occurrence < 24 hours before hospital admission (ischemic symptoms). The presenting symptoms must represent a change from the patient’s usual angina pattern (more frequent, longer in duration or lower in threshold).
4. Percutaneous coronary intervention (PCI) planned or anticipated for treatment of the index event, 2 days (-1/+2 days) after ACS symptoms and according to local or the European Guidelines for PCI (Silber S. 2005).
5. In addition to ischemic symptoms (described above), patients must have evidence of coronary artery disease. This may include any of the following findings:
o Documented previous MI
o Angiographic evidence of coronary artery disease
o Ischemic ECG changes, i.e. new or dynamic ST segment depression or T wave inversion in 2 or more contiguous electrocardiographic leads: at least 0.5 mm horizontal or down-sloping ST depression at the J point or up-sloping ST segment depression that remains at least 1 mm depressed 80 ms after the J point, or at least 1 mm T-wave inversion.
o Echocardiographic evidence of ischemia or infarction: a wall motion abnormality on echocardiogram (at least moderate hypokinesis ³ 2 standard image segments).
o Nuclear imaging evidence of ischemia or infarction: a reversible or fixed and unequivocal perfusion defect ³ 2 segments by radionuclide scintigraphy.
o Biological marker evidence of ischemia or new infarction: a transient elevation of creatine kinase-myocardial band (CK-MB) fraction and/or Troponin I or T (see Appendix G) above the upper limit of normal (ULN).
6. Patients willing to follow all study procedures including attendance to scheduled study visits, fasting prior blood draws and compliance with the investigational product regimen
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| E.4 | Principal exclusion criteria |
1. History of statin induced myopathy, or serious or hypersensitivity reaction to other HMG-CoA reductase inhibitors (statins).
2. Known homozygous familial hypercholesterolemia.
3. Any cholesterol lowering medication (HMG-CoA reductase inhibitors, fibrates, niacin (> 400 mg/day), ezetimibe, bile acid sequestrants, probucol or other prescription medications used to treat dyslipidemia) (Table 5) taken within 1 month prior to the Visit 1. Patients taking lipid lowering dietary supplements, anti-oxidants, or food additives may continue at their current dose. No new lipid lowering dietary supplements, anti-oxidants or food additives should be started for the duration of the study.
4. Pregnant women, women who are breast-feeding, and women of childbearing potential who are not using chemical or mechanical contraception, or who have a positive serum pregnancy test (serum b-HCG).
5. Sustained ST-segment elevation on 12-lead ECG
6. Active liver disease or hepatic dysfunction or alanine aminotransferase (ALT) elevation of ³ 2 x ULN
7. Serum creatinine > 2.0 mg/dL (176 mmol/L).
8. LDL-C £ 40 mg/dL (1.03 mmol/L) or triglycerides ³ 400 mg/dL (4.52 mmol/L)
9. Patients whose hormone replacement therapy (HRT) or oral contraceptive therapy (OCT) was initiated within the 3 months prior to the Visit 1.
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. Women with a history of cervical dysplasia would be permitted to enter the study provided they have 3 consecutive clear Papanicolaou (Pap) smears
11. Use of concomitant medications, as detailed in Table 5.
12. History of alcohol and/or drug abuse within the past 5 years.
13. Creatine kinase (CK) >3 x ULN and myocardial isoenzymes (CK-MB) <2 x ULN at Visit 1. If CK-MB is not available, should be considered: CK > 3 x ULN and Cardiac Troponin (I or T) = 0 at Visit 1.
14. Systolic hypotension (systolic blood pressure [SBP] < 90 mmHg) or poorly controlled hypertension (SBP > 200 mmHg or diastolic blood pressure > 110 mmHg) recorded since the onset of symptoms.
15. Planned therapeutic coronary intervention (other than primary PCI) or bypass surgery during the current hospitalization.
16. CABG or percutaneous coronary intervention (PCI) within the 3 months prior to Visit 1.
17. Occurrence of ventricular fibrillation, sustained ventricular tachycardia, complete heart block, new onset of fibrillation with uncontrolled ventricular rate (> 100 bpm), or paced ventricular rhythm within the preceding 4 weeks of Visit 1.
18. Stroke, sepsis, acute pericarditis, or any evidence of systemic or pulmonary embolus within the preceding 4 weeks of Visit 1.
19. Known uncontrolled hypothyroidism defined as a thyroid stimulating hormone (TSH) > 1.5 times the upper limit of normal (ULN) at Visit 1
20. Severe or uncontrolled diabetes (Type I or II) according to the investigator’s judgement.
21. Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the patient’s safety or successful participation in the study.
22. Participation in another investigational drug study and/or having ingested investigational drug £ 4 weeks, or according to local ethics committee requirements where a larger period is stipulated.
23. Patients already enrolled in the present study.
24. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site).
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint will be the percent change from baseline (Day 0) in ApoB/ApoA-I levels to 3 months. |
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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 | No |
| 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 | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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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End of study is defined as database lock which is the time point after which no patient will be exposed to study related activities.
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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 | 1 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
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