E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with ST segment elevation myocardial infarction |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053460 |
E.1.2 | Term | Antiplatelet therapy |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000891 |
E.1.2 | Term | Acute myocardial infarction |
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 |
The principle research question of this study is concerned with how the cardioprotective effect observed with Ticagrelor happens. Routine clinical practice is to give patients suffering from an acute heart attack antiplatelet therapy that has the effect of thinning the blood and reducing blood clot formation, improving the mircovascular circulation to the heart muscle and limiting cardiac muscle death during STEMI. However, the antiplatelet effect of Ticargelor is not immediate and the benefit observed with this drug is, therefore, hypothesized to be mediated via an alternative process.
The principal research question of this study is to explore whether the early benefit of Ticagrelor, in addition to it’s established antiplatelet action, is co-mediated by adenosine in maintaining and/or improving myocardial microcirculatory function.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are concerned with restoration of coronary blood flow resulting from PPCI (primary percutaneous coronary intervention) afforded between the two patient groups: one of which will receive clopidogrel, and the other which will recieve Ticagrelor. Measurements are as follows: 1. TIMI flow and TMBG pre/post PPCI 2. ST segment resolution at 60 minutes 3. OCT (optical coherence tomography) quantified clot volume pre/post PPCI (where feasible, safe and clinically possible) 4. Cardiac troponin-I at 0, 12 and 24 hours (+/- 2 hours for 12 and 24hr samples) 5. Cardiac MRI microvascular obstruction at 24-72hrs (where logistically feasible during the in-patient stay) and infarct size at 3 calendar months (+/- 14 days). 6. Myocardial Salvage and Salvage Index calculated on cardiac MRI 7. Trans-mural extent of Late Gadolinium Enhancement (LGE) on cardiac MRI 8. IMR calculated using Yong's formula |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For inclusion in the study subjects should fulfill the following criteria: 1. Provision of informed verbal consent prior to any study specific procedures taking place with written consent confirmed prior to in-patient cardiac MRI. 2. Male or female adult patient aged 18 – 90 years old 3. Any STEMI (ST elevation ≥ 2mm in contiguous chest leads) with chest pain symptom onset < 24 hours
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E.4 | Principal exclusion criteria |
Subjects should not enter the study if any of the following exclusion criteria are fulfilled: 1. Cardiogenic shock 2. Previous myocardial infarction in the infarct-related artery requiring intervention 3. Unfavourable coronary anatomy for PCI: left main/surgical or distal coronary disease 4. Already prescribed Ticagrelor at the time of admission 5. Factors affecting study drug administration/ absorption: vomiting or allergy to the IMP 6. Concomitant use of potent CYP3A4 inhibitors/ inducers (e.g ketoconazole and rifampicin) or CYP3A4 substrates with a narrow therapeutic window (e.g. cisapride and ergot alkaloids) or simvastatin / lovostatin >40mg oral dose. 7. Severe bleeding diathesis or current active bleeding 8. History of intracranial haemorrhage 9. Known Moderate or Severe hepatic impairment or abnormal liver function tests (ALT >5x ULN) at baseline (if available) 10. Severe asthma that has required hospital admission or significant bradycardia/ complete heart block diagnosed on ECG (contraindications to adenosine). 11. Severe co-morbidity with a life expectancy < 3 months. 12. Women of child bearing age unless confirmed by direct questioning that they are reproductively sterile or post-menopausal. 13. Concomitant treatment with anticoagulants. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure for this study is the index of myocardial resistance (IMR) measured post PPCI procedure. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of the PPCI procedure - approximately 1 hour after admission. |
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E.5.2 | Secondary end point(s) |
a TIMI flow and TMBG pre/post PPCI b ST segment resolution c OCT quantified clot volume pre/post PPCI (where feasible, safe and clinically possible) d Cardiac troponin – I at 0, 12 and 24 hours (+/- 2 hours for 12 and 24hr samples) e Cardiac MRI microvascular obstruction between 24-72 hours (where logistically feasible during the in-patient stay) and infarct size at 3 calendar months (+/- 14 days). f Myocardial Salvage and Salvage Index calculated on cardiac MRI g Trans-mural extent of Late Gadolinium Enhancement (LGE) on cardiac MRI h IMR calculated using Yong's formula |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a 1hr b 2hrs c 0-1hr d 0,12 and 24hrs e 24-72hrs and 3 months f 24-72hrs and 3 months g 24-72hrs and 3 months |
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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 | 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 | Yes |
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 end of the study is defined as the Last Subject Last Visit (LSLV) which for this study will be completion of the 12 month follow-up telephone call for the final participant. |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 6 |