E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Coronary Syndrom (ACS) |
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E.1.1.1 | Medical condition in easily understood language |
A range of conditions associated with sudden, reduced 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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051592 |
E.1.2 | Term | Acute coronary syndrome |
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 primary objective of this study is to assess and compare clinical safety of two ticagrelor-based antiplatelet de-escalation strategies with standard dual antiplatelet therapy (DAPT).
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is compare clinical efficacy of two ticagrelor-based antiplatelet de-escalation strategies with standard DAPT.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject has signed Informed Consent Form and is able to understand the purpose and procedures required for the study and is willing to participate in the study. 2. Subject is aged 18 and older. 3. Subject is able to understand and comply with the protocol requirements and instructions and is likely to complete the study as planned and is diagnosed with ACS, including ST-elevation myocardial infarction (STEMI), non ST elevation myocardial infarction (NSTEMI) or unstable angina (UA). The diagnosis of STEMI and NSTEMI will be made according to the Fourth Universal Definition of Myocardial Infarction, and UA will be diagnosed according to the 2020 European Society of Cardiology (ESC) Guidelines for the management of ACS in patients presenting without persistent ST-segment elevation (NSTE ACS). For patients with STEMI the following three inclusion criteria will have to be met: 1) new ST-elevation at the J-point in two contiguous leads with the cut-point ≥1 mm in all leads other than leads V2–V3, where the following cut-points apply: ≥2mm in men ≥40 years; ≥2.5 mm in men <40 years, or ≥1.5 mm in women regardless of age; or a new left bundle-branch block, and 2) the intention to perform primary percutaneous coronary intervention (PCI), and 3) detection of a rise and/or fall of cardiac troponin values with at least one value above the 99th percentile upper reference limit. For patients NSTEMI-ACS, at least two of the following three criteria will have to be met: 1) symptoms indicating myocardial ischemia; 2) ST-segment changes on electrocardiography indicating myocardial ischemia; 3) detection of a rise and/or fall of cardiac troponin values with at least one value above the 99th percentile upper reference limit; in addition to at least one of the following: - ≥60 years of age; - previous myocardial infarction or coronary artery by-pass grafting; - ≥50% stenosis in ≥2 coronary arteries; - previous ischemic stroke or Transient Ischemic Attack (TIA); - ≥50% carotid stenosis or cerebral revascularization; - diabetes mellitus; - peripheral artery disease; - chronic kidney disease with glomerular filtration rate <60 mL/min.
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E.4 | Principal exclusion criteria |
1. Contraindication to ticagrelor or/and ASA. 2. Need for use of any oral anticoagulation therapy. 3. Second or third grade atrio-ventricular block. 4. Previous stent thrombosis on treatment with ticagrelor. 5. End stage kidney disease with glomerular filtration rate <15 mL/min or on haemodialysis; 6. Administration of prasugrel during the index event; 7. Unreliability or lack of cooperation. 8. Pregnancy. 9. As per the Investigator (or his designee) judgment, subject cannot participate in the study for any reason (e.g., medical, psychiatric and/or social reason).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point os this project is the first occurrence of type 2, 3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) criteria, within 12 months of observation, in a time-to-event analysis. BARC type 2 bleeding is any clinically overt sign of haemorrhage that is actionable and requires diagnostic studies, hospitalization, or treatment by a health care professional. BARC type 3 bleeding is: a) overt bleeding with haemoglobin drop of 3 to <5 g/dL (provided it is related to bleed); transfusion with overt bleeding; b) overt bleeding with hemoglobin drop ≥5 g/dL (provided it is related to bleed); cardiac tamponade; bleeding requiring surgical intervention for control; bleeding requiring intravenous vasoactive agents; c) intracranial haemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision. BARC type 5 bleeding is fatal bleeding.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Within 12 months of observation, in a time-to-event analysis. |
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E.5.2 | Secondary end point(s) |
The key secondary endpoint is the composite of the first occurrence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke in a time-to-event analysis. Secondary bleeding end points include: 1) BARC type 3 or 5 bleeding; 2) Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding; 3) Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate, severe, or life-threatening bleeding; 4) International Society of Thrombosis and Haemostasis (ISTH) major bleeding. Other secondary endpoints include: 1) death from any cause; 2) death from Cardiovascular causes (CV); 3) myocardial infarction, 4) ischemic stroke; 5) definite or probable stent thrombosis; 6) adherence to study treatment; 7) dyspnea.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Is the composite of the first occurrence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke in a time-to-event analysis. |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 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 | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 60 |
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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For this study purposes “end of the trial” is defined as the last patient: last visit. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 11 |