Acute Coronary Syndromes
Conditions
Keywords
Acute Coronary Syndromes, Heart Disease, Percutaneous Coronary Intervention, P2Y12, NSTEMI
Brief summary
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
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.
Interventions
DRUGPlacebo
Administered once orally
DRUGPrasugrel
Administered orally
Sponsors
Daiichi Sankyo Co., Ltd.
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants With Occurrence of Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, Urgent Revascularization (UR), or Glycoprotein (GP) IIb/IIIa Inhibitor Bailout | First loading dose (LD) through 7 days after first LD | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | First loading dose (LD) through 7 days after first 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. |
| Percentage of Participants With Incidence of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke Through 30 Days From First Loading Dose (LD) | First LD through 30 days after first 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. |
| Percentage of Participants With Incidence of Cardiovascular (CV) Death or Myocardial Infarction (MI) Through 30 Days From First Loading Dose (LD) | First LD through 30 days after first 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. |
| Percentage of Participants With Incidence of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Urgent Revascularization (UR) Through 30 Days From First Loading Dose (LD) | First LD through 30 days after first 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. |
| Percentage of Participants With Incidence of Cardiovascular (CV) Death Through 30 Days From First Loading Dose (LD) | First LD through 30 days after first 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. |
| 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) | First LD through 30 days after first 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. |
| 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) | First LD through 30 days after first 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. |
| Change in Standardized Troponin From Baseline to Percutaneous Coronary Intervention (PCI) | Baseline, before PCI (not greater than 48 hours after randomization) | 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. |
| Percentage of Participants With Incidence of All Coronary Artery Bypass Graft (CABG) or Non-CABG Thrombolysis In Myocardial Infarction (TIMI) Major Bleeding | First loading dose (LD) through 7 days after first LD | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Summary of All-Cause Death | Randomization through 30 days | All deaths, regardless of possible relatedness, were adjudicated by the Clinical Endpoint Committee (CEC) and are reported in this table. |
Countries
Austria, Belgium, Canada, Czechia, Finland, France, Germany, Hungary, Israel, Italy, Latvia, Lithuania, Netherlands, Poland, Portugal, Romania, Slovakia, Sweden, Turkey (Türkiye)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Non Pre-treatment A placebo oral loading dose (LD) was given at the time of diagnosis and a 60 milligrams (mg) oral LD of prasugrel was given at the time of percutaneous coronary intervention (PCI) followed by 5 mg or 10 mg oral daily maintenance dose of prasugrel for 30 days. | 1,996 |
| Pre-treatment A 30 mg oral LD of prasugrel was given at diagnosis and a 30 mg oral dose of prasugrel was given at the time of PCI followed by 5 mg or 10 mg oral daily maintenance dose of prasugrel for 30 days. | 2,037 |
| Total | 4,033 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 21 | 16 |
| Overall Study | Entry Criteria not Met | 11 | 14 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Physician Decision | 19 | 21 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Sponsor Decision | 3 | 7 |
| Overall Study | Withdrawal by Subject | 14 | 19 |
Baseline characteristics
| Characteristic | Non Pre-treatment | Pre-treatment | Total |
|---|---|---|---|
| Age, Continuous | 63.59 years STANDARD_DEVIATION 11.239 | 63.80 years STANDARD_DEVIATION 11.27 | 63.69 years STANDARD_DEVIATION 11.254 |
| Sex: Female, Male Female | 558 Participants | 552 Participants | 1110 Participants |
| Sex: Female, Male Male | 1438 Participants | 1485 Participants | 2923 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 860 / 1,996 | 876 / 2,037 |
| serious Total, serious adverse events | 167 / 1,996 | 206 / 2,037 |
Outcome results
Primary
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.
Time frame: First loading dose (LD) through 7 days after first LD
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non Pre-treatment | The Percentage of Participants With Occurrence of Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, Urgent Revascularization (UR), or Glycoprotein (GP) IIb/IIIa Inhibitor Bailout | 9.77 percentage of participants |
| Pre-treatment | The Percentage of Participants With Occurrence of Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, Urgent Revascularization (UR), or Glycoprotein (GP) IIb/IIIa Inhibitor Bailout | 9.97 percentage of participants |
Secondary
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.
Time frame: Baseline, before PCI (not greater than 48 hours after randomization)
Population: All randomized participants who received at least 1 dose of study drug, had standardized troponin measured at baseline and before PCI (not greater than 48 hours after randomization).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Non Pre-treatment | Change in Standardized Troponin From Baseline to Percutaneous Coronary Intervention (PCI) | -11.24 ratio of assayed troponin/ULN | Standard Error 8.93 |
| Pre-treatment | Change in Standardized Troponin From Baseline to Percutaneous Coronary Intervention (PCI) | 2.82 ratio of assayed troponin/ULN | Standard Error 8.42 |
Secondary
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.
Time frame: First loading dose (LD) through 7 days after first LD
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non Pre-treatment | 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 | 7.57 percentage of participants |
| Pre-treatment | 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 | 8.64 percentage of participants |
Secondary
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.
Time frame: First LD through 30 days after first LD
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non Pre-treatment | 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) | 8.52 percentage of participants |
| Pre-treatment | 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) | 9.47 percentage of participants |
Secondary
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.
Time frame: First loading dose (LD) through 7 days after first LD
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non Pre-treatment | Percentage of Participants With Incidence of All Coronary Artery Bypass Graft (CABG) or Non-CABG Thrombolysis In Myocardial Infarction (TIMI) Major Bleeding | 1.35 percentage of participants |
| Pre-treatment | Percentage of Participants With Incidence of All Coronary Artery Bypass Graft (CABG) or Non-CABG Thrombolysis In Myocardial Infarction (TIMI) Major Bleeding | 2.55 percentage of participants |
Secondary
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.
Time frame: First LD through 30 days after first LD
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non Pre-treatment | Percentage of Participants With Incidence of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke Through 30 Days From First Loading Dose (LD) | 7.21 percentage of participants |
| Pre-treatment | Percentage of Participants With Incidence of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke Through 30 Days From First Loading Dose (LD) | 7.07 percentage of participants |
Secondary
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.
Time frame: First LD through 30 days after first LD
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non Pre-treatment | Percentage of Participants With Incidence of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Urgent Revascularization (UR) Through 30 Days From First Loading Dose (LD) | 7.31 percentage of participants |
| Pre-treatment | Percentage of Participants With Incidence of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Urgent Revascularization (UR) Through 30 Days From First Loading Dose (LD) | 7.71 percentage of participants |
Secondary
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.
Time frame: First LD through 30 days after first LD
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non Pre-treatment | Percentage of Participants With Incidence of Cardiovascular (CV) Death or Myocardial Infarction (MI) Through 30 Days From First Loading Dose (LD) | 6.51 percentage of participants |
| Pre-treatment | Percentage of Participants With Incidence of Cardiovascular (CV) Death or Myocardial Infarction (MI) Through 30 Days From First Loading Dose (LD) | 6.63 percentage of participants |
Secondary
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.
Time frame: First LD through 30 days after first LD
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non Pre-treatment | Percentage of Participants With Incidence of Cardiovascular (CV) Death Through 30 Days From First Loading Dose (LD) | 1.10 percentage of participants |
| Pre-treatment | Percentage of Participants With Incidence of Cardiovascular (CV) Death Through 30 Days From First Loading Dose (LD) | 0.69 percentage of participants |
Secondary
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.
Time frame: First LD through 30 days after first LD
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non Pre-treatment | 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) | 0.25 percentage of participants |
| Pre-treatment | 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) | 0.10 percentage of participants |
Other Pre-specified
Summary of All-Cause Death
All deaths, regardless of possible relatedness, were adjudicated by the Clinical Endpoint Committee (CEC) and are reported in this table.
Time frame: Randomization through 30 days
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Non Pre-treatment | Summary of All-Cause Death | During or Immediately Following a CABG Procedure | 5 participants |
| Non Pre-treatment | Summary of All-Cause Death | Intracranial Hemorrhage | 1 participants |
| Non Pre-treatment | Summary of All-Cause Death | Myocardial Infarction | 2 participants |
| Non Pre-treatment | Summary of All-Cause Death | Stroke, non-hemorrhagic | 0 participants |
| Non Pre-treatment | Summary of All-Cause Death | Cardiogenic Shock | 5 participants |
| Non Pre-treatment | Summary of All-Cause Death | Other Cardiovascular | 2 participants |
| Non Pre-treatment | Summary of All-Cause Death | Dysrhythmia | 0 participants |
| Non Pre-treatment | Summary of All-Cause Death | Non-Cardiac Hemorrhage, Not Intracranial | 0 participants |
| Non Pre-treatment | Summary of All-Cause Death | During or Immediately Following a PCI Procedure | 2 participants |
| Non Pre-treatment | Summary of All-Cause Death | Infection | 1 participants |
| Non Pre-treatment | Summary of All-Cause Death | Sudden Cardiac Death | 4 participants |
| Non Pre-treatment | Summary of All-Cause Death | Cancer | 0 participants |
| Non Pre-treatment | Summary of All-Cause Death | Congestive Heart Failure | 1 participants |
| Pre-treatment | Summary of All-Cause Death | Cancer | 1 participants |
| Pre-treatment | Summary of All-Cause Death | Congestive Heart Failure | 0 participants |
| Pre-treatment | Summary of All-Cause Death | Cardiogenic Shock | 5 participants |
| Pre-treatment | Summary of All-Cause Death | During or Immediately Following a CABG Procedure | 1 participants |
| Pre-treatment | Summary of All-Cause Death | During or Immediately Following a PCI Procedure | 1 participants |
| Pre-treatment | Summary of All-Cause Death | Myocardial Infarction | 1 participants |
| Pre-treatment | Summary of All-Cause Death | Dysrhythmia | 1 participants |
| Pre-treatment | Summary of All-Cause Death | Sudden Cardiac Death | 1 participants |
| Pre-treatment | Summary of All-Cause Death | Intracranial Hemorrhage | 1 participants |
| Pre-treatment | Summary of All-Cause Death | Stroke, non-hemorrhagic | 1 participants |
| Pre-treatment | Summary of All-Cause Death | Other Cardiovascular | 2 participants |
| Pre-treatment | Summary of All-Cause Death | Non-Cardiac Hemorrhage, Not Intracranial | 1 participants |
| Pre-treatment | Summary of All-Cause Death | Infection | 0 participants |