E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Damage and disease in the main arteries supplying the heart through inflammation or a build up of cholesterol containing plaques, restricting blood flow to the heart. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052086 |
E.1.2 | Term | Coronary arterial stent insertion |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 of this study is to assess the effects of a single loading regimen and two different maintenance regimens of ticagrelor on erythrocyte adenosine reuptake compared with standard regimens of clopidogrel. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: 1. Estimate the incidence of periprocedural myocardial infarction following elective PCI in patients pre-treated with either ticagrelor or clopidogrel 2. Assess the effects of two regimens of ticagrelor compared to clopidogrel on platelet aggregation in stable CAD patients managed with PCI 3. Determine the influence of genetic variability in CYP2C19 on the relative antiplatelet efficacy of clopidogrel compared to two regimens of ticagrelor in stable CAD patients managed with PCI
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of informed consent prior to any study specific procedures. 2. Male or female aged greater than 18 years. 3. Previous invasive coronary angiography with plan for PCI with coronary stent implantation for stable coronary artery disease.
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E.4 | Principal exclusion criteria |
1. Requirement for a chronic total occlusion to be crossed in order for any stent implantation to proceed. 2. Plan for coronary angiography with a view to PCI if appropriate (i.e. current coronary anatomy not known). 3. Intention to use platelet function tests or genotyping to guide antiplatelet therapy. 4. Known allergy to or intolerance of aspirin, clopidogrel or ticagrelor. 5. Treatment with antiplatelet medication apart from aspirin or clopidogrel that cannot be stopped 10 days prior to PCI (e.g. ticagrelor, prasugrel, dipyridamole, ticlopidine, abciximab, tirofiban), for example because of continuing indication. 6. Planned treatment or consideration of treatment with oral antiplatelet medication other than aspirin or clopidogrel following PCI. 7. Planned use of a glycoprotein IIb/IIIa antagonist for the PCI procedure. 8. Myocardial infarction within the past 12 months. 9. Current or planned use of an oral anticoagulant (e.g. warfarin, dabigatran, rivaroxaban, apixaban). 10. Previous history of intracranial haemorrhage or other intracranial pathology associated with increased bleeding risk. 11. Haemoglobin < 100 g/L or other evidence of active bleeding. 12. Peptic ulceration documented by endoscopy within the last 3 months unless healing proven by repeat endoscopy. 13. History of acute or chronic liver disease (e.g. cirrhosis). 14. Treatment in the last 10 days or requirement for ongoing treatment with a strong CYP3A4 inhibitor or inducer. 15. Requirement for ongoing treatment with simvastatin or lovastatin at a dose greater than 40 mg per day. 16. Treatment with a CYP3A4 substrate with a narrow therapeutic index (e.g. cyclosporine, quinidine). 17. End-stage renal failure requiring dialysis. 18. History of alcohol or drug abuse in the last year. 19. Co-morbidity associated with life expectancy less than 1 year. 20. Females of child-bearing potential unless negative pregnancy test at screening and willing to use effective contraception (i.e. established use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or barrier methods of contraception with spermicide or sole male partner with prior vasectomy and confirmed absence of sperm in ejaculate) for the duration of treatment with study medication. 21. Any other condition deemed by the investigator to place the patient at excessive risk of bleeding with ticagrelor. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Adenosine concentration in adenosine reuptake assay |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
30 days, pre and post maintenance dose |
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E.5.2 | Secondary end point(s) |
Platelet aggregation according to treatment and CYP2C19 genotype |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At time of PCI 2. At 30 days, pre maintenance dose 3. At 30 days, post maintenance dose |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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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The study will end when the last patient has had the last safety follow up visit at 30 days after discontinuation of study medication. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 | 31 |