E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011078 |
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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 is to demonstrate the superiority of ivabradine over placebo in the reduction of cardiovascular mortality, hospital admission for acute myocardial infarction, hospital admissions for new onset or worsening heart failure (composite endpoint). |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess the effect of ivabradine in the reduction of hospital admissions for acute coronary syndrome, hospital admissions for new onset or worsening heart failure, coronary revascularisations (composite endpoint), each endpoint of the previously mentioned composite endpoints, mortality related to coronary artery disease, total mortality, fatal and non-fatal myocardial infarctions. The tertiary objective is to assess the effect of ivabradine on the development of diabetes and metabolic syndrome, on the evolution of left ventricular ejection fraction, fractional shortening and end-diastolic dimension. |
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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 |
- HOLTER SUB-STUDY (Final Version - 03/01/06) "Effects of ivabradine on cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction. A three-year randomised double-blind placebo-controlled international multicentre study. Protocol number: CL3-16257-056." The purpose of this sub-study is to complete the cardiac safety assessment of ivabradine data from 24-hour Holter ECG recordings.
- ECHOCARDIOGRAPHY/NT-proBNP SUB-STUDY (Final Version - 03/01/2006) "Effects of ivabradine on cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction. A three-year randomised double-blind placebo-controlled international multicentre study". The purpose of this sub-study is to demonstrate the superiority of ivabradine versus placebo on the change from baseline in the left ventricule end systolic volume index over a 12 month treatment period and to assess the effect of ivabradine on other cardiac echographics parameters and on NT-proBNP serum concentrations. |
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E.3 | Principal inclusion criteria |
The main inclusion criteria will be: (1) history of coronary artery disease documented on a coronary angiography or by a previous myocardial infarction or a coronary revascularisation and (2) left ventricular systolic dysfunction defined as a left ventricular ejection fraction equal to 39% or lower on a two-dimensional echocardiography and a left ventricular dilatation defined as an echocardiographically measured short-axis internal dimension greater than 56 millimetres and (3) sinus rhythm and resting heart rate equal to or higher than 60 beats per minute and (4) informed consent obtained. |
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E.4 | Principal exclusion criteria |
The main exclusion criteria will be: (1) unstable cardiovascular condition (2) severe congestive heart failure (class IV of the classification of the New-York Heart Association) (3) contra-indications to the administration of ivabradine. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary objective (main purpose of the study), composite endpoint. Time to occurrence of the first event of one of the following: cardiovascular mortality, hospital admission for acute myocardial infarction, hospital admission for new onset or worsening heart failure. |
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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 | No |
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) | 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 | 28 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 460 |
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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End of the trial = the last visit of the last patient undergoing the trial. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |