A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction

Study Overview
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Brief Summary
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The purpose of this trial is to investigate the potential benefits/risks regarding pretreatment with prasugrel in non-ST-elevation myocardial infarction (NSTEMI) participants with elevated troponin scheduled for coronary angiography/percutaneous coronary intervention (PCI).

Detailed Description
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This trial consists of two arms. One arm is a non pre-treatment arm. Participants in this arm will receive placebo immediately after NSTEMI diagnosis and prior to the diagnostic coronary angiography. A 60 mg prasugrel loading dose will be given immediately after coronary angiography when proceeding to PCI. Subsequently, participants will receive daily maintenance doses of prasugrel until day 30. Participants who are greater than or equal to 75 years of age or who have a body weight less than 60 kilograms (kg) will receive 5 mg oral dose daily. All others will receive a 10 mg oral daily maintenance dose for 30 days. The other arm is a pre-treatment arm where participants will receive a split loading dose regimen with 30 mg of prasugrel administered immediately after NSTEMI diagnosis and prior to diagnostic coronary angiography. The remainder of the loading dose (30 mg) will be administered when the participants are proceeding to PCI. Subsequently, participants will receive daily maintenance doses of prasugrel until day 30. Participants who are greater than or equal to 75 years of age or who have a body weight less than 60 kg will receive 5 mg oral dose daily. All others will receive a 10 mg oral daily maintenance dose for 30 days.

Official Title
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A Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention (PCI) Or as Pretreatment At the Time of Diagnosis in Patients With Non-ST-Elevation Myocardial Infarction (NSTEMI): The ACCOAST Study

Conditions
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Acute Coronary Syndromes

Intervention / Treatment
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* Drug: Placebo
* Drug: Prasugrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have acute coronary syndrome consisting of non-ST-segment elevation with elevated troponin Scheduled for coronary angiography/PCI greater than or equal to 2 and less than 24 hours from time of planned randomization, but no more than 48 hours from randomization Must be eligible for treatment with prasugrel, aspirin (ASA), and a glycoprotein IIb/IIIa receptor (GPIIb/IIIa) inhibitor as per respective labels May be on a maintenance dose of clopidogrel 75 mg and must be able to switch to prasugrel Must be enrolled at a cardiac catheterization laboratory hospital or at a hospital/ambulance service affiliated with a cardiac catheterization laboratory hospital Exclusion Criteria: Present with ST-segment elevation myocardial infarction (STEMI) at the time of entry or randomization Have cardiogenic shock Have refractory ventricular arrhythmias Have New York Heart Association (NYHA) Class IV congestive heart failure (CHF) Have had cardiac arrest within 1 week of entry or randomization into the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non pre-treatment<br>A placebo oral loading dose is given at the time of diagnosis and a 60 milligrams (mg) oral loading dose of prasugrel is given at the time of PCI followed by 5 mg or 10 mg oral daily maintenance dose of prasugrel for 30 days. | Drug: Placebo<br>* Administered once orally<br>Drug: Prasugrel<br>* Administered orally<br>* Other names: CS-747;|
| Experimental: Split Loading Dose<br>A 30 mg oral loading dose of prasugrel is given at diagnosis and a 30 mg oral dose of prasugrel is given at the time of PCI followed by 5 mg or 10 mg oral daily maintenance dose of prasugrel for 30 days | Drug: Prasugrel<br>* Administered orally<br>* Other names: CS-747;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With Occurrence of Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, Urgent Revascularization (UR), or Glycoprotein (GP) IIb/IIIa Inhibitor Bailout | The percentage of participants is the total number of participants experiencing a CV death, MI, stroke, UR or GPIIb/IIIa Inhibitor bailout divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee. | First loading dose (LD) through 7 days after first LD | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With All-Cause Death, Myocardial Infarction (MI), Stroke, or All Coronary Artery Bypass Graft (CABG) and Non-CABG Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | The percentage of participants is the total number of participants experiencing an all-cause death, MI, stroke or CABG and non-CABG TIMI major bleeding divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee. | First loading dose (LD) through 7 days after first LD | 
| Percentage of Participants With Incidence of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke Through 30 Days From First Loading Dose (LD) | The percentage of participants is the total number of participants experiencing a CV death, MI, or stroke divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee. | First LD through 30 days after first LD | 
| Percentage of Participants With Incidence of Cardiovascular (CV) Death or Myocardial Infarction (MI) Through 30 Days From First Loading Dose (LD) | The percentage of participants is the total number of participants experiencing a CV death or MI divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee. | First LD through 30 days after first LD | 
| Percentage of Participants With Incidence of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Urgent Revascularization (UR) Through 30 Days From First Loading Dose (LD) | The percentage of participants is the total number of participants experiencing a CV death, MI, or UR divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee. | First LD through 30 days after first LD | 
| Percentage of Participants With Incidence of Cardiovascular (CV) Death Through 30 Days From First Loading Dose (LD) | The percentage of participants is the total number of participants experiencing a CV death divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee. | First LD through 30 days after first LD | 
| Percentage of Participants With Incidence of Definite or Probable Stent Thrombosis (ST) According to the Academic Research Consortium (ARC) Criteria Through 30 Days From First Loading Dose (LD) | ARC criteria were used to define ST. Definite ST is angiographic or pathologic confirmation of partial or total thrombotic occlusion within the peri-stent region, and at least one of the following additional criteria: acute ischemic symptoms; ischemic electrocardiogram changes; elevated cardiac biomarkers. Probable ST is any unexplained death within 30 days of stent implantation; any MI, which is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of ST and in the absence of any other obvious cause. The percentage of participants is the total number of participants experiencing a definite or probable stent thrombosis divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee. | First LD through 30 days after first LD | 
| Percentage of Participants With All-cause Death, Myocardial Infarction (MI), Stroke, or All Coronary Artery Bypass Graft (CABG) and Non-CABG Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding Through 30 Days From First Loading Dose (LD) | The percentage of participants is the total number of participants experiencing an all-cause death, MI, stroke or CABG and non-CABG TIMI major bleeding divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee. | First LD through 30 days after first LD | 
| Change in Standardized Troponin From Baseline to Percutaneous Coronary Intervention (PCI) | Standardized troponin is defined as the ratio of the assayed troponin value divided by the upper limit of normal (ULN). Least Squares (LS) means were obtained from an Analysis of Covariance (ANCOVA) model with treatment as a fixed effect and baseline standardized troponin as a covariate. | Baseline, before PCI (not greater than 48 hours after randomization) | 
| Percentage of Participants With Incidence of All Coronary Artery Bypass Graft (CABG) or Non-CABG Thrombolysis In Myocardial Infarction (TIMI) Major Bleeding | The percentage of participants is the total number of participants experiencing a CABG or non-CABG TIMI major bleeding divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee. | First loading dose (LD) through 7 days after first LD | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Coronary Syndromes, Heart Disease, Percutaneous Coronary Intervention, P2Y12, NSTEMI