E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ST elevated myocard infarction followed by PCI |
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E.1.1.1 | Medical condition in easily understood language |
Acute heart infarct treated with stent setting |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 prove noninferiority regarding safety and effectiveness of 30-45 day of DAPT followed by Prasugrelmonotherapy versus standard 12 months of DAPT in patients admitted for STEMI treated by primary PCI.
The ancillary objective of the study is to prove that OCT-guided revascularization completion by staged PCI is superior to an angioguided approach in patients with multivessel disease who have received guideline-based treatment of the culprit lesion.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria at index procedure All STEMI patients who are planned to be treated with PCI providing a witnessed oral informed consent: ST segment elevation myocardial infarction: Chest discomfort suggestive of cardiac ischemia ≥20 min at rest, with 1 of the following ECG features: • ST segment elevation ≥2 contiguous ECG leads • new or presumably new left bundle branch block
Inclusion Criteria at 30-45 days • Compliance to DAPT with no regimen modifications (Non-adherence Academic Research Consortium 0; see section 6.4.4) • No occurrence of significant event (such as MI, unplanned revascularisation, stent thrombosis, stroke, major vascular complication/bleeding BARC Types 3 or greater). • Successful revascularization: - Successful delivery and deployment of the Study device(s), with final residual stenosis of <30% (visually) for all target lesions. • Complete revascularization performed when more than 1 significant lesion, during staged procedure(s) occurring within 15 days from the index procedure. Physiologic assessment highly recommended for lesions with stenosis between 50% and 90%.
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E.4 | Principal exclusion criteria |
Exclusion criteria • Patients on oral anticoagulation • Contraindication to P2Y12 inhibitors and/or to Cardioaspirin or to any of the excipients (hypersensitivity, history of any stroke or transient ischemic attack within the last 12 months, active bleeding or haemorrhagic diathesis, fibrin-specific fibrinolytic therapy less than 24 h before randomization, severe hepatic dysfunction (Child-Pugh C), history of asthma induced by the administration of salicylates or substances with a similar action, notably non-steroidal anti-inflammatory medicines, history of gastrointestinal perforation or acute gastrointestinal ulcers, severe cardiac failure (NYHA grade III or IV), combination with methotrexate at doses of 15 mg/week or more). • Patients who have received P2Y12 inhibitors other than Prasugrel in the ambulance (Ticagrelor or Clopidogrel loading dose) or are already on P2Y12 inhibitors, may be enrolled in the protocol, provided that the Prasugrel loading dose is administered at admission, according to current guidelines recommendations (see section 5.2.2). • Concomitant oral or i.v. therapy with strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, grapefruit juice >1L/day), CYP3A substrates with narrow therapeutic indices (e.g., cyclosporine, quinidine), or strong CYP3A inducers (e.g., rifampin) • rifampicin, phenytoin, carbamazepine, dexamethason, phenobarbital • Platelet count <100.000/μL at the time of screening • Anemia (hemoglobin <10 g/dL) at the time of screening • Comorbidities associated with life expectancy <1 year • Pregnancy, giving birth within the last 90 days, willing to have pregnancy during the study period or lactation (see appendix III for women of childbearing potential) • PCI indication for stent thrombosis or previous history of definite stent thrombosis • Non-deferrable major surgery on DAPT after PCI • Cardiogenic shock • Out of hospital cardiac arrest (OHCA) unless survivors of ventricular arrythmia with prompt return of spontaneous circulation (ROSC) • Patients with severe renal impairment: creatinine clearance ≤30 ml/min/1.73 m2 (as calculated by MDRD formula for estimated GFR). • Patients participating in another interventional (device of drug trial) within the previous 12 months or patients to whom an investigational drug was administered in the 30 days prior to screening, or 5 half-lives of the study drug, whichever is longer. • No informed consent
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E.5 End points |
E.5.1 | Primary end point(s) |
Demonstrate the non inferority of a Prasugrel-based short DAPT (30-45 days) followed by 11-month Prasugrel monotherapy versus standard 12 months DAPT regimen by assessing: - Incidence of Net Adverse Clinical Events (NACE) at 11 months post DAPT randomization as composite of death, MI, stroke or BARC bleeding 3 or 5
The co-primary objective is to demonstrate in patients with multivessel disease compare the superiority of an Optical Coherence Tomography (OCT)-guided complete revascularization completion as compared to a standardn angiography-guided complete revascularization completion strategy in STEMI patients with MVD by assessing: Post-procedural Minimal Stent Area (MSA)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
11 months after DAPT randomisation |
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E.5.2 | Secondary end point(s) |
With respect to the antithrombotic therapy analysis, the secondary exploratory objectives primarily include the assessment of the primary endpoint for superiority if non-inferiority is demonstrated and the assessment of differences between the two antithrombotic regimens compared in the trial for the following endpoints (key secondary endpoints): • Composite of major adverse cardiac and cerebrovascular events (MACCE) defined as cardiovascular death, myocardial infarction, or ischaemic stroke • BARC type 3 or 5 events
With respect to the imaging-based analysis, the secondary exploratory objectives include the assessment of differences between OCT- and angiography-guided revascularization completion in terms of 12-month target vessel failure (TVF), defined as the composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target vessel revascularization. In the subgroup of patients with multivessel disease, the interaction between antithrombotic therapy regimens (i.e. short DAPT followed by Prasugrel monotherapy versus standard DAPT) and the type of guidance to achieve revascularization completeness (i.e., OCT- versus angiography-guided) for the primary and key secondary endpoints will be formally explored by Cox proportional hazards regression models including the two factors as covariates alongside their interaction term.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | 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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
12 months DAPT ( as per the current guidelines for ACS patients) |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |