E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients having successfully undergone coronary artery bypass graft (CABG) surgery |
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E.1.1.1 | Medical condition in easily understood language |
Patients having had a heart surgery |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 main objective of this study is to investigate the impact on platelet function of increasing either the aspirin dose (from 75 mg to 160 mg) or dosing frequency (to 75 mg BID) over 3 months in patients undergoing elective CABG surgery. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate inhibition of the COX pathway functionally through assessment of platelet aggregation in response to arachidonic acid and collagen in whole blood before (with 75 mg aspirin OD), and at various time points after CABG surgery with three different dosages of aspirin, 75 mg OD, 75 mg BID or 160 mg OD
2. To evaluate inhibition of the COX pathway pharmacologically through serum TxB2 levels (a stable metabolite of TxA2) before, and at various time points after CABG surgery with three different dosages of aspirin, 75 mg OD, 75 mg BID or 160 mg OD
3. To determine whether platelet turnover impacts on the efficacy of the different dosing regimens to induce sustained platelet inhibition
4. To evaluate possible relationships between the antiplatelet effects of different aspirin dosing strategies and inflammatory biomarkers following CABG surgery |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Stable CAD patients scheduled to undergo elective CABG surgery
- Willing to participate and able to provide informed consent
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E.4 | Principal exclusion criteria |
- Patients taking drugs other than aspirin that are known to influence platelet function, including nonsteroidal anti-inflammatory drugs (NSAIDs, including COX-2 selective anti-inflammatory drugs), GPIIbIIIa inhibitors, clopidogrel, dipyridamole, warfarin or acenocoumarol within 7 days of enrolment
- Hemorrhagic diathesis or known platelet dysfunction
- Patients with chronic renal failure requiring dialysis
- Patients with a platelet count outside the 100 000 to 450 000/μL range
- Patients with severe anaemia (Haemoglobin < 8g/dl) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Inhibition of the COX pathway functionally through assessment of platelet aggregation in response to arachidonic acid and collagen in whole blood |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Before surgery, before hospital discharge (days 4-7 after surgery), after 4 weeks of therapy and after 3(-4) months of therapy |
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E.5.2 | Secondary end point(s) |
- Inhibition of the COX pathway pharmacologically through serum TxB2 levels (a stable metabolite of TxA2)
- Platelet turnover
Inflammatory biomarkers
- Bleeding symptoms |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Before surgery, before hospital discharge (days 4-7 after surgery), after 4 weeks of therapy and after 3(-4) months of therapy |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard dose of aspirin (75 mg daily) |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | No |
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
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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 | |