E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stable coronary artery disease. |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011078 |
E.1.2 | Term | Coronary artery disease |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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 |
To determine if ticagrelor (a blood thinning medication) reduces the levels of plasma high-sensitivity troponin I (a protein in the blood that is associated with increased risk of heart attacks in the future) in patients with stable heart disease but evidence of high-risk features on heart scans. |
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E.2.2 | Secondary objectives of the trial |
a) To determine if ticagrelor (a blood thinning medication) reduces the levels of plasma high-sensitivity troponin I (a blood test that is associated with increased risk of heart attacks in the future) in patients with stable coronary heart disease and no evidence of high-risk features on heart scans.
b) To determine if ticagrelor reduces the level of plasma high-sensitivity troponin I (hsTnI) over 1 year
c) To determine if ticagrelor will reduce the size of fatty deposits (plaques) or calcium (hardening) in the coronary arteries
d) To assess the evolution of plaque rupture and recovery on PET scanning over time |
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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 |
Reproducibility and Natural History of 18F Sodium Fluoride Positron Emission Tomography Assessment of the Vulnerable Plaque
The objective of this sub-study is to confirm the reproducibility (i.e. do lesions remain consistent in demonstrating the presence or absence of tracer uptake when the scan is repeated at an interval of 1 week?) and assess the natural history (i.e. over what time period do lesions continue to demonstrate tracer uptake, and what is the rate of development of new 18F-F positive plaques?) of 18F-F PET imaging. |
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E.3 | Principal inclusion criteria |
1) Patients aged ≥40 years with angiographically proven multivessel coronary artery disease defined as at least two major epicardial vessels with any combination of either (a) >50% luminal stenosis, or (b) previous revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery).
2) Provision of informed consent prior to any study specific procedures
3) Receiving aspirin
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E.4 | Principal exclusion criteria |
1. An acute coronary syndrome within the last 12 months 2. An indication for dual anti-platelet therapy, such as drug eluting stent 3. Receiving thienopyridine therapy such as clopidogrel or prasugrel 4. Percutaneous coronary intervention or coronary artery bypass graft surgery within the last 3 months 5. Inability or unwilling to give informed consent 6. Women who are pregnant, breastfeeding or of child-bearing potential (women who have experienced menarche, are pre-menopausal and have not been sterilised) will not be enrolled into the trial 7. Known hypersensitivity to ticagrelor or one of its excipients 8. Active pathological bleeding or bleeding diathesis 9. Significant thrombocytopenia: platelets <100 x 109 /L 10. History of intracranial haemorrhage 11. Moderate to severe liver impairment (Child’s Grade B or C) 12. Maintenance therapy with strong CYP3A4 inhibitors, such as ketoconazole, nefazodone, ritonavir, indinavir, atazanavir, or clarithromycin 13. Major intercurrent illness or life expectancy <1 year 14. Renal dysfunction (eGFR ≤30 mL/min/1.73 m2) 15. Contraindication to iodinated contrast agents 16. Planned coronary revascularization or major non-cardiac surgery in the next 12 months 17. Maintenance therapy with simvastatin or lovastatin at doses greater than 40mg daily 18. Receiving oral anticoagulants including warfarin, rivaroxaban, dabigatran or apixaban.
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E.5 End points |
E.5.1 | Primary end point(s) |
Plasma high sensitivity cardiac troponin I (hsTnI) concentration in patients with coronary 18F-fluoride uptake |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
30 days after beginning treatment. |
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E.5.2 | Secondary end point(s) |
a) Plasma hsTnI concentrations at 30 days in patients without coronary 18F-fluoride uptake. b) High sensitivity cardiac troponin I (hsTnI) concentration at 30 days in total study population. c) Plasma hsTnI concentrations at 1 year d) Total calcium score at 1 year e) Plaque volume at 1 year at the site of baseline coronary 18F-fluoride uptake f) Reproducibility of 18F-fluoride uptake detected on PET imaging at 1 week f) Natural history of 18F-fluoride uptake over 1 year
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) At 30 days b) At 30 days c) At 1 year d) At 1 year e) At 1 year f) At 1 week g) At 1 year |
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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 | 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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 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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There will be additional blood and data analysis following LVLS to make full use of the information gathered during 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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |