E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
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 |
Investigate the effect of simvastatin on biochemical and functional measures of endothelial function in patients with heart failure. |
|
E.2.2 | Secondary objectives of the trial |
Measures of surrogate markers of cardiac function including NT pro BNP, intermedin and adrenomedullin (all measured in blood samples) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible for the study, patients must be over 18 years of age and have a diagnosis of heart failure based on transthoracic echocardiogram showing left ventricular ejection fraction less than 35 % with New York Heart Association symptom class II - IV. Patients will typically be receiving maximal medical therapy for heart failure. Patients must also be able to give informed consent and be able to attend the department for investigations. |
|
E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they have a history of diabetes mellitus (fasting glucose > 7mmol/l), uncontrolled hypertension (BP > 140/90 mmHg) or are receiving the thienopyridine derivative clopidogrel. Patients will also be excluded if they have abnormal liver function (ALT of AST > 3 times upper limit of normal) or have had a previously documented adverse reaction to statin therapy or hypersensitivity to simvastatin or any of the excipients. Females will be excluded if they are pregnant or lactating. Any patient who has an adverse reaction to statin therapy following initiation of treatment, will be excluded from further participation in the study. Patients taking potent CYP3A4 inhibitors (eg. itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin) will be excluded. Patients taking ciclosporin, gemfibrozil, or >1g/day niacin will also be excluded. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints will be difference in biochemical and functional measures of endothelial function between placebo and treatment arms of the study. Biochemical markers compared will be: nitric oxide superoxide peroxynitrite tetrahydrobiopterin NT pro BNP adrenomedullin intermedin
Functional measures will be: fore arm mediated dilatation and pulse contour analysis |
|
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 | No |
E.6.5 | Efficacy | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
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 | 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
|
Last visit of the last subject undergoing the trial. |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 |