E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bleeding among high-risk patients with percutanous coronary intervention with at least one drug-eluting stent |
|
E.1.1.1 | Medical condition in easily understood language |
Bleeding among high-risk patients with percutanous coronary intervention with at least one drug-eluting stent |
|
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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065608 |
E.1.2 | Term | Percutaneous coronary intervention |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
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 determine the impact of antiplatelet monotherapy with ticagrelor alone versus Dual Antiplatelet Therapy (DAPT) with ticagrelor plus aspirin for 12 months in reducing clinically relevant bleeding among high-risk patients undergoing PCI who have completed a 3-month course of aspirin plus ticagrelor. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to determine the impact of antiplatelet monotherapy with ticagrelor alone versus DAPT with ticagrelor plus aspirin for 12 months in reducing major ischemic adverse events among high-risk patients undergoing PCI who have completed a 3-month course of aspirin plus ticagrelor. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Must meet AT LEAST ONE clinical inclusion criterion: - Adult patients ≥ 65 years of age - Female gender - Troponin positive acute coronary syndrome - Established vascular disease defined as previous MI, documented PAD or CAD/PAD revascularization - Diabetes mellitus treated with medications or insulin - Chronic kidney disease defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 or creatinine clearance (CrCl) <60 ml/min
Must meet AT LEAST ONE angiographic inclusion criterion: - Multivessel coronary artery disease (CAD) * - Target lesion requiring total stent length >30mm - Thrombotic target lesion(s) - Bifurcation lesion(s) with Medina X,1,1 classification requiring at least 2 stents - Left main (≥50%) or proximal LAD (≥70%) lesion - Calcified target lesion(s) requiring atherectomy
* The diagnosis of multivessel CAD may be established with the angiogram performed at enrollment or an earlier angiogram. A vessel previously treated with either a stent or bypass graft may also be considered diseased for purposes of meeting the multivessel CAD angiographic inclusion criterion. |
|
E.4 | Principal exclusion criteria |
Subjects should not enter the study if any of the following exclusion criteria are met: - Under 18 years of age - Contraindication to aspirin - Contraindication to ticagrelor - Planned surgery within 90 days - Planned coronary revascularization (surgical or percutaneous) within 90 days - Need for chronic oral anticoagulation - Prior stroke - Dialysis-dependent renal failure - Active bleeding or extreme-risk for major bleeding (e.g. acute gastrointestinal ulcer or history of chronic gastrointestinal ulceration, gastrointestinal pathology with a raised risk for bleeding, malignancies with a raised risk for bleeding) - Salvage PCI or STEMI presentation. - Liver cirrhosis - Life expectancy < 1 year - Unable or unwilling to provide informed consent - Women of child bearing potential as defined below: A woman is considered of childbearing potential (WOBCP) following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. - Fibrinolytic therapy within 24 hours of index PCI - Concomitant therapy with a strong cytochrome P-450 3A inhibitor or inducer - Platelet count < 100,000 mm3 - Requiring ongoing treatment with aspirin ≥325 mg daily |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary bleeding endpoint of the present study is the time to first occurrence of clinically relevant bleeding, defined as Bleeding Academic Research Consortium (BARC) Types 2, 3 or 5 bleeding.
The primary ischemic endpoint of the present study is the time to first occurrence of confirmed all-cause death, non-fatal myocardial infarction, or stroke. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
time from randomisation to death or last follow-up |
|
E.5.2 | Secondary end point(s) |
Secondary Bleeding Endpoints Time to first occurrence of: • Types 3 or 5 bleeding according to definitions from BARC • Minor or major bleeding according to definitions from Thrombolysis in Myocardial Infarction (TIMI) • Moderate or severe or life-threatening bleeding according to definitions from GUSTO • Major bleeding according to definitions from International Society of Thrombosis or Hemostasis (ISTH)
Secondary Ischemic Endpoints Time to first occurrence of: • cardiovascular death, non-fatal myocardial infarction, ischemic stroke or clinically-driven revascularization • cardiovascular death, non-fatal myocardial infarction or ischemic stroke • definite or probable stent thrombosis • cardiovascular death • non-fatal myocardial infarction • cardiovascular death, non-fatal myocardial infarction or definite or probable stent thrombosis • ischemic stroke • all-cause mortality |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
time from randomisation to death or last follow-up |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
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) | 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 | 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 | 2 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Canada |
Germany |
India |
Israel |
Italy |
Poland |
Spain |
United States |
|
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
|
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |