E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Aspirin resistance: Vascular diseases are common problems and aspirin is used as an anti-platelet drug to prevent thrombosis. However, aspirin's anti-platelet effect may not be uniform in all patients. From a biochemical perspective, aspirin resistance refers to patients who do not display an adequate degree of platelet inhibition on formal laboratory tests. Published data suggest that 5 - 45% of patients are 'aspirin resistant'. The mechanisms of aspirin resistance are poorly understood.
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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 aims of this proposed study are to use a repeated measures crossover trial design in order to:
assess the reproducibility of aspirin resistance in healthy control individuals, as defined by standard optical platelet aggregometry,
characterise the contribution of genetic polymorphisms in candidate genes, specifically the cyclooxygenase and adenosine 5-diphosphate receptor genes, to the phenomenon of aspirin resistance.
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E.2.2 | Secondary objectives of the trial |
The secondary outcome measures are:
the assessment of the reproducibility of aspirin response as defined by other platelet function tests (PFA-100, thromboxane levels),
the contribution of other genetic polymorphisms to the phenomenon of aspirin resistance,
and the correlation between the various platelet function tests used in this study. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Healthy individuals, age 18 - 60 years. |
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E.4 | Principal exclusion criteria |
Use of other anti-platelet drugs (thienopyridines, GPIIb/IIIa antagonists, dipyridamole) because these drugs would also interfere with platelet function assays; Use of other non-steroidal anti-inflammatory drugs, because of pharmacodynamic interactions; History of dyspepsia or peptic ulceration requiring treatment with proton pump inhibitor or H2-antagonist, in view of the increased risk of gastrointestinal haemorrhagic complications; History of systemic inflammatory diseases, in view of the need for these patients to take anti-inflammatory drugs; History of asthma; Use of other medications including aspirin (including herbal preparations); Family or personal history of bleeding disorders, in order to reduce the potential for haemorrhagic complications; Use of oral anticoagulants; Platelet count outside the normal range (150,000 - 450,000 / ml), as these patients require further investigation and aspirin use is contra-indicated in patients with significant thrombocytopaenia; Significant anaemia (Hb < 10g/dl), as these patients may require further investigation; Recent major surgery, in view of the potential for haemorrhagic complications; Known significant malignant disease, in view of the potential for haemorrhagic complications; Known aspirin allergy; Women of childbearing potential, except in the following circumstances for the duration of the trial: o Monogamous relationship and partner sterilized, or o For personal reasons not sexually active, or o Use of double barrier methods of contraception (in these situations the patient will sign an additional consent form to indicate that they will take measures to avoid becoming pregnant during the trial); History of lactose intolerance; History of gout; History of severe renal or hepatic dysfunction; Planned surgery during participation in trial; Excessive alcohol ingestion (>40 units per week); Inability to provide informed consent. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measures for this proposed study are the assessment of the reproducibility of aspirin response in healthy control individuals, as defined by standard optical platelet aggregometry, and the contribution of the Cyclooxygenase and Adenosine 5-diphosphate receptor gene polymorphisms to the phenomenon of aspirin resistance. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Information not present in EudraCT |
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.8.5 | 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 | 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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The trial will end when 150 individuals have been included in the 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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |