Acute Coronary Syndromes, Coronary Arteriosclerosis
Conditions
Brief summary
The sponsors of this investigational drug are developing prasugrel (also known as CS-747) as a possible treatment for patients with acute coronary syndrome (heart attack or chest pain) who need, or are expected to need, a percutaneous coronary intervention (PCI; also called a balloon angioplasty). Prasugrel was compared with Clopidogrel to determine which drug is better at reducing deaths, future heart attacks, or stroke.
Interventions
DRUGPrasugrel
Administered orally
DRUGClopidogrel
Administered orally
Sponsors
Daiichi Sankyo
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
* A person who has been diagnosed with acute coronary syndrome and is to undergo a percutaneous coronary intervention. * A person who is of the legal age of 18 and is mentally competent to provide a signed written informed consent. * If a woman is of childbearing potential (i.e., before menopause), she must test negative for pregnancy and agree to use a reliable method of birth control.
Exclusion criteria
* A person who has had an ischemic stroke within the last 3 months or a hemorrhagic stroke at any time in the past. * A person who has active internal bleeding or has a history of a bleeding disorder. * Individuals who are at an increased risk of bleeding based on laboratory criteria evaluated by the treatment physician or on medication that can cause bleeding. * A person who has liver disease; for example, cirrhosis. * A person who has a condition such as alcoholism, mental illness, or is drug dependent. * A person who has cardiogenic shock, a refractory ventricular arrhythmia, or congestive heart failure (class IV).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | Randomization up to 15 months | The endpoint in this measure is a combination of CV death, nonfatal MI, or nonfatal stroke. The data is presented by the study population, which is represented as follows: 1) subjects who presented with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI), 2) subjects who presented with ST segment elevation myocardial infarction (STEMI), and 3) all subjects with acute coronary syndromes (ACS) (i.e. all subjects with UA/NSTEMI or STEMI). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | First dose of study drug up to 15 months (while at risk) | TIMI classification for major and minor bleeding in the subset of subjects who did not undergo a coronary artery bypass operation (CABG) were defined as follows: Major bleeding: any intracranial hemorrhage (ICH) OR any clinically overt bleeding (including bleeding evident on imaging studies) associated with a fall in hemoglobin (Hgb) of ≥5 grams/deciliter (gm/dL)from baseline. Minor Bleeding: any clinically overt bleeding associated with a fall in Hgb of ≥3 gm/dL but \<5 gm/dL from baseline. Major bleeding events were further examined as events that were deemed life threatening and/or fatal. |
| Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Urgent Target Vessel Revascularization (UTVR) | Randomization to 30 days; randomization to 90 days | The endpoint in this measure is a combination of CV death, nonfatal MI, or UTVR. Results are reported for the All ACS subject population for the 30 and 90 day periods. |
| Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | Randomization to 30 days; randomization to 90 days | The endpoint in this measure is a combination of CV death, nonfatal MI, or nonfatal stroke. Results are reported for the All ACS population for the 30 and 90 day periods. |
| Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, or Rehospitalization for Cardiac Ischemic Events | Randomization up to 15 months | The endpoint in this measure is a combination of CV death, nonfatal MI, nonfatal stroke, or rehospitalization for cardiac ischemic events. Results are reported for the All ACS population. |
| Number of Subjects Reaching the Composite Endpoint of All-Cause Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | Randomization up to 15 months | The endpoint in this measure is a combination of all-cause death, nonfatal MI, or nonfatal stroke. Results are reported for the All ACS population. |
Countries
United States
Participant flow
Recruitment details
Acute Coronary Syndromes (ACS) includes subjects presenting with unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI).
Participants by arm
| Arm | Count |
|---|---|
| Prasugrel Oral loading dose of six 10 mg prasugrel tablets and four placebo tablets matched to clopidogrel, followed by an oral maintenance dose of prasugrel one 10 mg tablet and one placebo tablet matched to clopidogrel once daily | 6,813 |
| Clopidogrel Oral loading dose of four 75 mg clopidogrel tablets and six placebo tablets matched to prasugrel, followed by an oral maintenance dose of one 75 mg clopidogrel tablet and one placebo tablet matched to prasugrel once daily | 6,795 |
| Total | 13,608 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Less than 6 months on study drug | 9 | 7 |
| Overall Study | Lost to follow up | 6 | 10 |
| Overall Study | Other | 0 | 3 |
| Overall Study | Unable to attend termination visit | 53 | 51 |
| Overall Study | Withdrawal of consent | 342 | 323 |
Baseline characteristics
| Characteristic | Clopidogrel | Total | Prasugrel |
|---|---|---|---|
| Age Continuous | 60.9 years STANDARD_DEVIATION 11.4 | 60.9 years STANDARD_DEVIATION 11.3 | 60.9 years STANDARD_DEVIATION 11.2 |
| Race/Ethnicity, Customized African | 187 Participants | 392 Participants | 205 Participants |
| Race/Ethnicity, Customized Asian | 64 Participants | 124 Participants | 60 Participants |
| Race/Ethnicity, Customized Caucasian | 6274 Participants | 12537 Participants | 6263 Participants |
| Race/Ethnicity, Customized Hispanic | 256 Participants | 525 Participants | 269 Participants |
| Race/Ethnicity, Customized Other | 14 Participants | 30 Participants | 16 Participants |
| Region of Enrollment Africa | 200 participants | 404 participants | 204 participants |
| Region of Enrollment Europe | 3439 participants | 6875 participants | 3436 participants |
| Region of Enrollment Middle East | 613 participants | 1219 participants | 606 participants |
| Region of Enrollment North America | 2146 participants | 4310 participants | 2164 participants |
| Region of Enrollment Pacifica | 133 participants | 266 participants | 133 participants |
| Region of Enrollment South America | 264 participants | 534 participants | 270 participants |
| Sex: Female, Male Female | 1818 Participants | 3523 Participants | 1705 Participants |
| Sex: Female, Male Male | 4977 Participants | 10085 Participants | 5108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5,217 / 6,741 | 5,187 / 6,716 |
| serious Total, serious adverse events | 1,731 / 6,741 | 1,675 / 6,716 |
Outcome results
Primary
Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke
The endpoint in this measure is a combination of CV death, nonfatal MI, or nonfatal stroke. The data is presented by the study population, which is represented as follows: 1) subjects who presented with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI), 2) subjects who presented with ST segment elevation myocardial infarction (STEMI), and 3) all subjects with acute coronary syndromes (ACS) (i.e. all subjects with UA/NSTEMI or STEMI).
Time frame: Randomization up to 15 months
Population: Intention-to-treat (ITT) population consisting of all subjects with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) who may or may not have received study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | UA/NSTEMI (n=5044, n=5030) | 469 Participants |
| Prasugrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | STEMI (n=1769, n=1765) | 174 Participants |
| Prasugrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | All ACS (n=6813, n=6795) | 643 Participants |
| Clopidogrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | All ACS (n=6813, n=6795) | 781 Participants |
| Clopidogrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | UA/NSTEMI (n=5044, n=5030) | 565 Participants |
| Clopidogrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | STEMI (n=1769, n=1765) | 216 Participants |
Comparison: For UA/NSTEMI populationp-value: 0.00295% CI: [0.726, 0.927]Gehan-Wilcoxon
Comparison: For STEMI populationp-value: 0.01995% CI: [0.649, 0.968]Gehan-Wilcoxon
Comparison: For All ACS populationp-value: <0.00195% CI: [0.732, 0.902]Gehan-Wilcoxon
Secondary
Number of Subjects Reaching the Composite Endpoint of All-Cause Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke
The endpoint in this measure is a combination of all-cause death, nonfatal MI, or nonfatal stroke. Results are reported for the All ACS population.
Time frame: Randomization up to 15 months
Population: Intention-to-treat (ITT) population consisting of all randomized All ACS subjects who may or may not have received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Subjects Reaching the Composite Endpoint of All-Cause Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | 692 Participants |
| Clopidogrel | Number of Subjects Reaching the Composite Endpoint of All-Cause Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | 822 Participants |
p-value: <0.00195% CI: [0.751, 0.919]Log Rank
Secondary
Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, or Rehospitalization for Cardiac Ischemic Events
The endpoint in this measure is a combination of CV death, nonfatal MI, nonfatal stroke, or rehospitalization for cardiac ischemic events. Results are reported for the All ACS population.
Time frame: Randomization up to 15 months
Population: Intention-to-treat (ITT) population consisting of all randomized All ACS subjects who may or may not have received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, or Rehospitalization for Cardiac Ischemic Events | 797 Participants |
| Clopidogrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, or Rehospitalization for Cardiac Ischemic Events | 938 Participants |
p-value: <0.00195% CI: [0.762, 0.921]Log Rank
Secondary
Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke
The endpoint in this measure is a combination of CV death, nonfatal MI, or nonfatal stroke. Results are reported for the All ACS population for the 30 and 90 day periods.
Time frame: Randomization to 30 days; randomization to 90 days
Population: Intention-to-treat (ITT) population consisting of all randomized All ACS subjects who may or may not have received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | All ACS (Through 30 days) | 389 Participants |
| Prasugrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | All ACS (Through 90 days) | 462 Participants |
| Clopidogrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | All ACS (Through 30 days) | 502 Participants |
| Clopidogrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke | All ACS (Through 90 days) | 573 Participants |
Comparison: Through 30 daysp-value: <0.00195% CI: [0.672, 0.876]Log Rank
Comparison: Through 90 daysp-value: <0.00195% CI: [0.705, 0.901]Log Rank
Secondary
Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Urgent Target Vessel Revascularization (UTVR)
The endpoint in this measure is a combination of CV death, nonfatal MI, or UTVR. Results are reported for the All ACS subject population for the 30 and 90 day periods.
Time frame: Randomization to 30 days; randomization to 90 days
Population: Intention-to-treat (ITT) population consisting of all randomized All ACS subjects who may or may not have received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Urgent Target Vessel Revascularization (UTVR) | All ACS (Through 30 days) | 399 Participants |
| Prasugrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Urgent Target Vessel Revascularization (UTVR) | All ACS (Through 90 days) | 472 Participants |
| Clopidogrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Urgent Target Vessel Revascularization (UTVR) | All ACS (Through 30 days) | 504 Participants |
| Clopidogrel | Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Urgent Target Vessel Revascularization (UTVR) | All ACS (Through 90 days) | 588 Participants |
Comparison: Through 30 daysp-value: <0.00195% CI: [0.688, 0.894]Log Rank
Comparison: Through 90 daysp-value: <0.00195% CI: [0.703, 0.896]Log Rank
Secondary
Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events
TIMI classification for major and minor bleeding in the subset of subjects who did not undergo a coronary artery bypass operation (CABG) were defined as follows: Major bleeding: any intracranial hemorrhage (ICH) OR any clinically overt bleeding (including bleeding evident on imaging studies) associated with a fall in hemoglobin (Hgb) of ≥5 grams/deciliter (gm/dL)from baseline. Minor Bleeding: any clinically overt bleeding associated with a fall in Hgb of ≥3 gm/dL but \<5 gm/dL from baseline. Major bleeding events were further examined as events that were deemed life threatening and/or fatal.
Time frame: First dose of study drug up to 15 months (while at risk)
Population: Treated subjects with adverse events were considered at risk from the first dose of study drug up through 7 days after permanent study drug discontinuation, or the subjects' discontinuation visit; or from randomization through 464 days, whichever is earlier. Adverse events classified as study drug related were included in the at risk set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prasugrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | LT - Symptomatic intracranial hemorrage (ICH) | 19 Participants |
| Prasugrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | TIMI Major Bleeding - Life-threatening (LT) | 85 Participants |
| Prasugrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | LT - Requiring inotropes | 21 Participants |
| Prasugrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | TIMI Major Bleeding | 146 Participants |
| Prasugrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | LT - Requiring surgical intervention | 19 Participants |
| Prasugrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | LT - Requiring transfusion (>=4 units) | 45 Participants |
| Prasugrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | LT - Fatal | 21 Participants |
| Prasugrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | TIMI Minor Bleeding | 164 Participants |
| Prasugrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | TIMI Major or Minor Bleeding | 303 Participants |
| Clopidogrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | TIMI Minor Bleeding | 125 Participants |
| Clopidogrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | TIMI Major or Minor Bleeding | 231 Participants |
| Clopidogrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | TIMI Major Bleeding | 111 Participants |
| Clopidogrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | TIMI Major Bleeding - Life-threatening (LT) | 56 Participants |
| Clopidogrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | LT - Fatal | 5 Participants |
| Clopidogrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | LT - Symptomatic intracranial hemorrage (ICH) | 17 Participants |
| Clopidogrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | LT - Requiring inotropes | 8 Participants |
| Clopidogrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | LT - Requiring transfusion (>=4 units) | 30 Participants |
| Clopidogrel | Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events | LT - Requiring surgical intervention | 19 Participants |
Comparison: For non-CABG TIMI Major or Minor Bleedingp-value: 0.00295% CI: [1.107, 1.559]Log Rank
Comparison: For non-CABG TIMI Major Bleedingp-value: 0.02995% CI: [1.028, 1.683]Log Rank
Comparison: For the subset of non-CABG TIMI Major Bleeding - Life-threatening events (LT)p-value: 0.01595% CI: [1.083, 2.126]Log Rank
Comparison: For the subset of non-CABG TIMI Major Bleeding - LT - Fatalp-value: 0.00295% CI: [1.158, 11.113]Log Rank
Comparison: For the subset of non-CABG TIMI Major Bleeding - LT - Symptomatic intracranial hemorrage (ICH)p-value: 0.73695% CI: [0.582, 2.152]Log Rank
Comparison: For the subset of non-CABG TIMI Major Bleeding - LT - Requiring inotropesp-value: 0.01695% CI: [1.159, 5.908]Log Rank
Comparison: For the subset of non-CABG TIMI Major Bleeding - LT - Requiring surgical interventionp-value: 0.99595% CI: [0.528, 1.885]Log Rank
Comparison: For the subset of non-CABG TIMI Major Bleeding - LT - Requiring transfusion (\>=4 units)p-value: 0.08495% CI: [0.945, 2.379]Log Rank
Comparison: For the subset of non-CABG TIMI Minor Bleedingp-value: 0.02295% CI: [1.04, 1.656]Log Rank