E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
The cardinal sign of decreased blood flow to the heart is chest pain experienced as tightness around the chest and radiating to the left arm and the left angle of the jaw. |
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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 | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071111 |
E.1.2 | Term | Non ST segment elevation 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 |
To test the hypothesis that, for subjects with non-ST-segment
elevation myocardial infarction (NSTEMI) with elevated troponin who are scheduled for coronary angiography/percutaneous coronary intervention (PCI), a prasugrel loading dose (LD) given at the time of qualifying diagnosis is superior to a prasugrel LD given at the time of the PCI procedure, as measured by a reduction in the composite endpoint of cardiovascular (CV) death, myocardial infarction (MI), stroke, urgent revascularization (UR) or GPIIb/IIIa inhibitor bailout through 7 days from randomization. |
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E.2.2 | Secondary objectives of the trial |
To evaluate net clinical benefit (composite of all-cause death, MI, stroke
or all coronary artery bypass graft [CABG] and non-CABG Thrombolysis in Myocardial Infarction [TIMI] major bleeding) through 7 days from randomization.
The key safety objective is to evaluate all CABG or non-CABG TIMI major bleeding through 7 days from randomization. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria:
[1] Present with acute coronary syndromes (ACS) consisting of non-STsegment elevation (NSTEMI) with elevated troponin. NSTEMI is defined as a history of chest discomfort or ischemic symptoms of ≥10 minutes duration at rest ≤48 hours prior to entry into the study with no evidence of persistent ST-segment elevation. Elevated troponin is defined as a troponin T or I ≥1.5 times the upper limit of normal (ULN).
[2] Are scheduled for coronary angiography/PCI ≥2 and <24 hours from the time of planned randomization. If necessary due to timing constraints,
coronary angiography/PCI may be scheduled the next day with the intention to perform coronary angiography/PCI within 24 hours, but
definitely no later than 48 hours from randomization.
[3] Must be eligible for treatment with prasugrel, ASA, and a GPIIb/IIIa
inhibitor as per respective labels.
[4] May be on a maintenance dose of clopidogrel 75 mg and must be able to switch to prasugrel.
[5] Must be enrolled at a cardiac catheterization laboratory hospital or at a
hospital/ambulance service affiliated with a cardiac catheterization laboratory hospital.
[6] Must be of a legal age (and at least 18 years of age) and of competent
mental condition to provide written informed consent before entering the
study. Informed consent must be signed by the study participant or
authorized representative, if allowed by local rules and regulations.
[7] Must not be of child-bearing potential (1 year post-menopausal or
surgically sterile). |
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E.4 | Principal exclusion criteria |
Cardiovascular Exclusion Criteria:
[1] Present with ST-segment elevation myocardial infarction (STEMI) at the time of entry or randomization into the study defined as follows:
ST-segment elevation myocardial infarction is defined as a history of
chest discomfort or ischemic symptoms of >20 minutes duration at rest ≤14 days prior to entry into the study with one of the following present on at least one ECG prior to randomization:
a) ST-segment elevation ≥1 mm in two or more contiguous ECG
leads.
b) New or presumably new left bundle branch block (LBBB).
c) ST-segment depression ≥1 mm in two anterior precordial leads
(V1 through V4) with clinical history and evidence suggestive of
true posterior infarction.
[2] Have cardiogenic shock (systolic blood pressure <90 mm Hg associated
with clinical evidence of end-organ hypoperfusion, or subjects requiring
vasopressors to maintain systolic blood pressure over 90 mm Hg and
associated with clinical evidence of end-organ hypoperfusion).
[3] Have refractory ventricular arrhythmias.
[4] Have New York Heart Association (NYHA) Class IV congestive heart failure (CHF); see Attachment TADF.3 for NYHA CHF classifications.
[5] Have had cardiac arrest within 1 week of entry or randomization into the study.
Bleeding Risk Exclusion Criteria
[6] Have any of the following:
(a) Prior history of hemorrhagic or ischemic stroke, a transient
ischemic attack (TIA), or sub-arachnoid hemorrhage.
(b) History of intracranial neoplasm, arteriovenous malformation, or
aneurysm.
[7] Have received fibrinolytic therapy within 48 hours of entry or
randomization into the study.
[8] Have active pathological bleeding or history of bleeding diathesis.
[9] Have clinical findings, in the judgment of the investigator, associated with an increased risk of bleeding.
[10] Have known anemia.
[11] Have had recent surgery (within 4 weeks of entry into the study) or are scheduled to undergo surgery within the next 2 months.
Prior/Concomitant Therapy Exclusion Criteria:
[12] Have received a loading dose of a thienopyridine (ticlopidine,
clopidogrel or prasugrel) or a maintenance dose of prasugrel or
ticlopidine within 7 days of entry into the study.
[13] Are receiving a GPIIb/IIIa inhibitor (eptifibatide, tirofiban, or abciximab).
[14] Are receiving warfarin or other coumarin derivatives.
[15] Are receiving or will receive oral anticoagulation or other oral
antiplatelet therapy (except aspirin [ASA]) that cannot be safely
discontinued within the next 3 months.
[16] Are receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX2) inhibitors that cannot be discontinued or are anticipated to require >2 weeks of daily treatment with NSAID or COX2 inhibitors during the study.
General Exclusion Criteria:
[17] Are investigator site personnel directly affiliated with the study or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
[18] Are employed by Eli Lilly & Company, Ube Industries Limited, or
Daiichi Sankyo Company Limited (that is, employees, temporary
contract workers, or designees responsible for the conduct of the study) Immediate family of Lilly employees may participate in Lilly-sponsored clinical studies but are not permitted to participate at a Lilly facility. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
[19] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry or are presently enrolled in another drug or device study.
[20] Have previously completed or withdrawn from this study or any other study investigating prasugrel.
[21] Are women who are known to be pregnant, who have given birth within the past 90 days, or who are breastfeeding.
[22] Have a concomitant medical illness (for example, terminal malignancy) that, in the opinion of the investigator, is associated with reduced survival over the expected study treatment period (approximately 1 month).
[23] Have rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption.
[24] Have severe hepatic impairment defined as Child Pugh Class C.
[25] Have a condition associated with poor treatment compliance, including alcoholism, mental illness, or drug dependence.
[26] Have a history of intolerance or allergy to ASA or approved
thienopyridines (ticlopidine, clopidogrel, or prasugrel) or GPIIb/IIIa
inhibitors (eptifibatide, tirofiban, or abciximab). |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate if a prasugrel loading dose (LD) given at the time
of qualifying diagnosis is superior to a prasugrel LD given at the time of the PCI procedure in subjects with non-ST-segment elevation myocardial infarction (NSTEMI) with elevated troponin who are scheduled for coronary angiography/percutaneous coronary intervention (PCI). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy measure is a composite of clinical endpoints committee (CEC)-adjudicated CV death, MI, stroke, UR, or GPIIb/IIIa inhibitor bailout through 7 days from randomization. |
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E.5.2 | Secondary end point(s) |
To assess net clinical benefit (composite of all-cause death, MI, stroke
or all coronary artery bypass graft [CABG] and non-CABG Thrombolysis in Myocardial Infarction [TIMI] major bleeding) through 7 days from randomization.
To compare the 2 prasugrel LD regimens in terms of the
incidence of the following:
• CV death, MI, or stroke through 30 days from randomization
• CV death or MI through 30 days from randomization
• CV death, MI, or UR through 30 days from randomization
• CV death through 30 days from randomization
• Definite or probable stent thrombosis according to the Academic Research Consortium criteria through 30 days from randomization
• Net clinical benefit (composite of all-cause death, MI, stroke, or all TIMI major bleeding) through 30 days from randomization |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
30 days from randomzation. |
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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 | Yes |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Two different loading dose regimens of prasugrel are compared. |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
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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 | 2 |
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 | 2 |
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 |