Cardiovascular Diseases, Heart Diseases
Conditions
Brief summary
The purpose of this study is to evaluate the effects of a drug known as CS-747 (also known as prasugrel) on subjects having a procedure called a percutaneous coronary intervention (also referred to as PCI) in which a doctor will attempt to open a blocked vessel (or vessels) in the heart using a catheter (a long thin tube) that has a small balloon on the end. In many cases, patients who have this procedure receive a stent, a small wire spring that helps keep the vessel open.
Interventions
DRUGPrasugrel (CS-747)
Administered orally
DRUGClopidogrel
Administered orally
Sponsors
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients must be candidates for elective or urgent PCI with intended coronary stenting. * Men or non-pregnant women (that is, postmenopausal women, women who are surgically sterile, or women of childbearing potential who have a negative urine or serum pregnancy test) who are greater than or equal to 18 and less than or equal to 75 years of age.
Exclusion criteria
* Patients must not have planned PCI procedure as initial treatment for an acute ST-elevation acute myocardial infarction (STEMI) * Patients must not be receiving or will receive oral anticoagulation therapy that cannot be safely discontinued for the duration of the study * Patients must not have cardiogenic shock or severe congestive heart failure * Patients must not have active internal bleeding or history of bleeding diathesis * Patients must not have prior history of hemorrhagic cerebrovascular accident (CVA) or nonhemorrhagic CVA within 2 years of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Non-coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding Events | randomization though 30 days after percutaneous coronary intervention (PCI) | Number of participants with non-coronary artery bypass graft (non-CABG) Thrombolysis In Myocardial Infarction (TIMI) Major or Minor bleeding. A major bleed was defined as an intracranial hemorrhage OR a clinically overt hemorrhage with a \>5 g/dL decrease in hemoglobin. A minor bleed was defined as a clinically overt hemorrhage with a hemoglobin decrease \>=3 g/dL and \<= 5 g/dL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Major Adverse Cardiovascular Events (MACE) | randomization though 30 days after percutaneous coronary intervention (PCI) | Number of participants with any of the following: death, nonfatal myocardial infarction, stroke, total or subtotal occlusion of the target vessel, urgent target vessel revascularization, recurrent ischemia requiring hospitalization. |
| Number of Participants With Non-Coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | randomization though 30 days after percutaneous coronary intervention (PCI) | Number of participants with non-coronary artery bypass graft (non-CABG) Thrombolysis In Myocardial Infarction (TIMI) Major or Minor bleeding. A major bleed was defined as an intracranial hemorrhage OR a clinically overt hemorrhage with a \>5 g/dL decrease in hemoglobin. |
| Number of Participants With Non-CABG TIMI Major or Minor Bleeding Plus MACE | randomization though 30 days after percutaneous coronary intervention (PCI) | Number of participants with non-coronary artery bypass graft (non-CABG) Thrombolysis In Myocardial Infarction (TIMI) Major or Minor bleeding or MACE. Major bleed was defined as an intracranial hemorrhage OR a clinically overt hemorrhage with a \>5 g/dL decrease in hemoglobin. Minor bleed was defined as a clinically overt hemorrhage with a hemoglobin decrease \>=3 g/dL and \<= 5 g/dL. MACE is any of the following:death, nonfatal myocardial infarction, stroke, total or subtotal occlusion of the target vessel, urgent target vessel revascularization, recurrent ischemia requiring hospitalization |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prasugrel (CS-747) 40 mg LD/7.5 mg MD Prasugrel (CS-747) 40-mg oral loading dose (LD) at time of percutaneous coronary intervention (PCI) followed by 7.5-mg oral maintenance dose (MD), once daily, for 29-34 days | 199 |
| Prasugrel (CS-747) 60 mg LD/10 mg MD Prasugrel (CS-747) 60 mg oral loading dose (LD) at time of PCI followed by 10 mg oral maintenance dose (MD), once daily, for 29-34 days | 200 |
| Prasugrel (CS-747) 60-mg LD/15-mg MD Prasugrel (CS-747) 60-mg oral loading dose (LD) at time of PCI followed by 15-mg oral maintenance dose (MD), once daily, for 29-34 days | 251 |
| Clopidogrel Clopidogrel 300-mg oral LD at time of PCI followed by an oral 75-mg MD; taken once a day | 254 |
| Total | 904 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 5 | 9 | 9 |
| Overall Study | Death | 0 | 0 | 3 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 2 | 1 | 1 |
| Overall Study | Protocol entry criteria not met | 1 | 1 | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 4 | 1 | 3 |
Baseline characteristics
| Characteristic | Total | Clopidogrel | Prasugrel (CS-747) 60-mg LD/15-mg MD | Prasugrel (CS-747) 60 mg LD/10 mg MD | Prasugrel (CS-747) 40 mg LD/7.5 mg MD |
|---|---|---|---|---|---|
| Age Continuous | 59.2 years STANDARD_DEVIATION 9.03 | 58.4 years STANDARD_DEVIATION 9.17 | 59.4 years STANDARD_DEVIATION 8.97 | 58.7 years STANDARD_DEVIATION 9.15 | 60.4 years STANDARD_DEVIATION 8.72 |
| Age, Customized >18 and <= 65 years | 661 participants | 195 participants | 185 participants | 152 participants | 129 participants |
| Age, Customized <=18 years | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Age, Customized > 65 years | 243 participants | 59 participants | 66 participants | 48 participants | 70 participants |
| Race/Ethnicity, Customized African descent | 48 participants | 9 participants | 15 participants | 14 participants | 10 participants |
| Race/Ethnicity, Customized Caucasian | 824 participants | 238 participants | 226 participants | 180 participants | 180 participants |
| Race/Ethnicity, Customized East/Southeast Asian | 3 participants | 0 participants | 1 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic | 16 participants | 2 participants | 7 participants | 2 participants | 5 participants |
| Race/Ethnicity, Customized Other | 3 participants | 2 participants | 1 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Western Asian | 10 participants | 3 participants | 1 participants | 3 participants | 3 participants |
| Region of Enrollment Canada | 181 participants | 46 participants | 48 participants | 44 participants | 43 participants |
| Region of Enrollment United States | 723 participants | 208 participants | 203 participants | 156 participants | 156 participants |
| Sex: Female, Male Female | 208 Participants | 59 Participants | 53 Participants | 49 Participants | 47 Participants |
| Sex: Female, Male Male | 696 Participants | 195 Participants | 198 Participants | 151 Participants | 152 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 147 / 199 | 157 / 200 | 192 / 251 | 195 / 254 |
| serious Total, serious adverse events | 17 / 199 | 9 / 200 | 18 / 251 | 22 / 254 |
Outcome results
Primary
Number of Participants With Non-coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding Events
Number of participants with non-coronary artery bypass graft (non-CABG) Thrombolysis In Myocardial Infarction (TIMI) Major or Minor bleeding. A major bleed was defined as an intracranial hemorrhage OR a clinically overt hemorrhage with a \>5 g/dL decrease in hemoglobin. A minor bleed was defined as a clinically overt hemorrhage with a hemoglobin decrease \>=3 g/dL and \<= 5 g/dL.
Time frame: randomization though 30 days after percutaneous coronary intervention (PCI)
Population: Patients who received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel (CS-747) 40-mg LD/7.5-mg MD | Number of Participants With Non-coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding Events | 3 participants |
| Prasugrel (CS-747) 60-mg LD/10-mg MD | Number of Participants With Non-coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding Events | 4 participants |
| Prasugrel (CS-747) 60-mg LD/15-mg MD | Number of Participants With Non-coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding Events | 4 participants |
| Clopidogrel | Number of Participants With Non-coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding Events | 3 participants |
| Prasugrel (CS-747) Combined | Number of Participants With Non-coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding Events | 11 participants |
p-value: 0.933Fisher Exact
p-value: 0.59Log Rank
Secondary
Number of Participants With Major Adverse Cardiovascular Events (MACE)
Number of participants with any of the following: death, nonfatal myocardial infarction, stroke, total or subtotal occlusion of the target vessel, urgent target vessel revascularization, recurrent ischemia requiring hospitalization.
Time frame: randomization though 30 days after percutaneous coronary intervention (PCI)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel (CS-747) 40-mg LD/7.5-mg MD | Number of Participants With Major Adverse Cardiovascular Events (MACE) | 15 participants |
| Prasugrel (CS-747) 60-mg LD/10-mg MD | Number of Participants With Major Adverse Cardiovascular Events (MACE) | 15 participants |
| Prasugrel (CS-747) 60-mg LD/15-mg MD | Number of Participants With Major Adverse Cardiovascular Events (MACE) | 17 participants |
| Clopidogrel | Number of Participants With Major Adverse Cardiovascular Events (MACE) | 24 participants |
| Prasugrel (CS-747) Combined | Number of Participants With Major Adverse Cardiovascular Events (MACE) | 47 participants |
p-value: 0.945Fisher Exact
p-value: 0.26Log Rank
Secondary
Number of Participants With Non-CABG TIMI Major or Minor Bleeding Plus MACE
Number of participants with non-coronary artery bypass graft (non-CABG) Thrombolysis In Myocardial Infarction (TIMI) Major or Minor bleeding or MACE. Major bleed was defined as an intracranial hemorrhage OR a clinically overt hemorrhage with a \>5 g/dL decrease in hemoglobin. Minor bleed was defined as a clinically overt hemorrhage with a hemoglobin decrease \>=3 g/dL and \<= 5 g/dL. MACE is any of the following:death, nonfatal myocardial infarction, stroke, total or subtotal occlusion of the target vessel, urgent target vessel revascularization, recurrent ischemia requiring hospitalization
Time frame: randomization though 30 days after percutaneous coronary intervention (PCI)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel (CS-747) 40-mg LD/7.5-mg MD | Number of Participants With Non-CABG TIMI Major or Minor Bleeding Plus MACE | 17 participants |
| Prasugrel (CS-747) 60-mg LD/10-mg MD | Number of Participants With Non-CABG TIMI Major or Minor Bleeding Plus MACE | 19 participants |
| Prasugrel (CS-747) 60-mg LD/15-mg MD | Number of Participants With Non-CABG TIMI Major or Minor Bleeding Plus MACE | 20 participants |
| Clopidogrel | Number of Participants With Non-CABG TIMI Major or Minor Bleeding Plus MACE | 27 participants |
| Prasugrel (CS-747) Combined | Number of Participants With Non-CABG TIMI Major or Minor Bleeding Plus MACE | 56 participants |
p-value: 0.37Fisher Exact
Secondary
Number of Participants With Non-Coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding
Number of participants with non-coronary artery bypass graft (non-CABG) Thrombolysis In Myocardial Infarction (TIMI) Major or Minor bleeding. A major bleed was defined as an intracranial hemorrhage OR a clinically overt hemorrhage with a \>5 g/dL decrease in hemoglobin.
Time frame: randomization though 30 days after percutaneous coronary intervention (PCI)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prasugrel (CS-747) 40-mg LD/7.5-mg MD | Number of Participants With Non-Coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | 1 participants |
| Prasugrel (CS-747) 60-mg LD/10-mg MD | Number of Participants With Non-Coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | 1 participants |
| Prasugrel (CS-747) 60-mg LD/15-mg MD | Number of Participants With Non-Coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | 1 participants |
| Clopidogrel | Number of Participants With Non-Coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | 2 participants |
| Prasugrel (CS-747) Combined | Number of Participants With Non-Coronary Artery Bypass Graft (Non-CABG) Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding | 3 participants |
p-value: 1Fisher Exact
p-value: 0.544Log Rank