E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This will be a randomized, multicentre, double-blind, placebo controlled, parallel group trial in patients at moderate risk of CHD events; cardiovascular death, MI, or stroke. |
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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 evaluate the clinical effects of a 100 mg/day enteric-coated acetylsalicylic acid versus placebo in the reduction of CVD events in patients at moderate risk of major CHD events (10-20% 10-year risk; approximate 20-30% 10-year risk of CVD). |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the safety and tolerability of the 100 mg/day enteric-coated acetylsalicylic acid versus placebo in the same patient population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The inclusion criteria are based on the National Heart, Lung and Blood Institute (NHLBI) Framingham Heart Study (FHS) cardiovascular risk predictors.45 The ability of the selected inclusion criteria to procure a moderate risk population was confirmed by modeling the criteria with PROCAM, Framingham and SCORE risk calculators. All consenting patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
Males aged 50 years and above with 2 or 3 risk factors
Male Risk Factors
Males aged 60 and above Elevated cholesterol (Tchol>200 mg/dL or LDL>130 mg/dL; as measured at screening) irrespective of current treatment Current smoking*: defined as any cigarette smoking in the past 12 months (*smoking cannot be the sole risk factor for males aged 60 and above) Low HDL cholesterol (HDL<40 mg/dL; as measured at screening) Elevated blood pressure (SBP>140 mmHg; as measured at screening) Currently on any medication to treat high blood pressure Positive family history of early CHD (a first-degree relative [father, mother, brother, sister, son, daughter] suffered a heart attack [myocardial infarction] before the age of 60 years)
Females aged 60 and above with 3 or more risk factors
Female Risk Factors Elevated cholesterol (Tchol>240 mg/dL or LDL>160 mg/dL; as measured at screening) Current smoking: defined as any cigarette smoking in the past 12 months Low HDL cholesterol (HDL<40 mg/dL; as measured at screening) Elevated blood pressure (SBP>140 mmHg; as measured at screening) Currently on any medication to treat high blood pressure Positive family history of early CHD (a first-degree relative [father, mother, brother, sister, son, daughter] suffered a heart attack [myocardial infarction] before the age of 60 years)
An understanding and willingness to comply with trial procedures and has given written informed consent to participate in the trial |
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E.4 | Principal exclusion criteria |
Patients presenting with any of the following will not be included in the trial: 1. Clinical history of CVD, MI, stroke, coronary artery angioplasty or stenting, coronary artery bypass graft, relevant arrhythmias, or congestive heart failure 2. Patients who are at higher than moderate risk on the basis of: a) their diabetes status (i.e. those with Type I or Type II diabetes actively treated with drug therapy) b) other factors known to the investigator (e.g. a male patient over 60 years of age with 4 or more risk factors) c) the currently used national risk score 3. Any medical condition, or psychiatric or substance abuse disorder, that, in the opinion of the investigator, is likely to affect the patient’s ability to complete the study or precludes the patient’s participation in the study 4. Lactating women or women of childbearing potential 5. Known increased risk of bleeding, e.g., gastric or duodenal ulcer, genitourinary causes or other bleeding disorders. 6. Known/diagnosed reflux esophagitis. 7. Moderately impaired renal function based on the clinical judgment of the investigator. 8. Severe liver disease or damage based on the clinical judgment of the investigator. 9. A history of asthma induced by administration of salicylates or substances with a similar action, notably NSAIDs 10. History of hypersensitivity or drug allergy to acetylsalicylic acid 11. A definite indication for acetylsalicylic acid therapy, other anti-platelet drug, or anticoagulant in the opinion of the physician 12. Chronic, frequent (> 5 days/month) use of NSAIDs, COX-2 inhibitors or metamizole (acetaminophen/paracetamol and other non NSAID pain medications will be permitted) 13. Current participation in any other trials involving investigational products within 30 days prior to the Screening Visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be a composite outcome consisting of the first occurrence of cardiovascular death, MI, or stroke. The time to event is defined as the number of days from the date of randomization to the date of the event confirmed by adjudication.
A patient for whom a primary endpoint occurs is required to leave the study. Patients in whom no primary endpoint occurred by the end of the study will undergo administrative censoring at study termination. Patients lost to follow-up will be censored at their date of last contact (telephone or clinic visit).
Secondary Efficacy Endpoints A composite outcome of the time to the first occurrence of cardiovascular death, ACS (Acute Coronary Syndrome), or stroke * Time to the first non-fatal MI * Time to the first MI (fatal or non-fatal)* Time to first occurrence of a non-fatal stroke* Time to first occurrence of fatal or non-fatal stroke* Analyses will also be presented for ischemic and hemorrhagic stroke separately, if appropriate. Time to cardiovascular death* Time to/ incidence of all-cause mortality Time to first occurrence of/ incidence of all cancers excluding non melanoma skin cancer |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
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) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | Yes |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 30 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 300 |
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 | Yes |
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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Although the planned treatment duration is 60 months, the actual duration will be event-driven. The study will be terminated when 1488 primary endpoint events (cardiovascular death, MI, or stroke) have been observed. A patient for whom a primary endpoint occurs will be considered to have reached the End-of-Study |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |