Clopidogrel to Prasugrel in Acute Coronary Syndrome (ACS) Patients
- Conditions
- Acute Coronary Syndrome
- Interventions
- Registration Number
- NCT01115738
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
This study will evaluate the use of a prasugrel 60 mg loading dose (LD) administered during percutaneous coronary intervention (PCI) with and without a prior LD of clopidogrel on platelet inhibition in patients presenting with acute coronary syndrome (ACS). Platelet inhibition following a prasugrel LD in clopidogrel pretreated patients' will be determined in a time-dependent manner for two different prasugrel loading doses (30 mg and 60 mg). Understanding the effects of this combination on platelet inhibition will provide guidance to physicians on the use of prasugrel in patients who have already been pretreated with clopidogrel.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 282
- Participants hospitalized with acute coronary syndrome (ACS) [unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), or ST elevation myocardial infarction (STEMI)] as determined by the investigator, and who are anticipated to undergo percutaneous coronary intervention (PCI) as a treatment for the ACS event within 24 hours of the clopidogrel/placebo loading dose
- Participants provide signed informed consent form (ICF)
- Participants weigh at least 60 kilograms (kg) at the time of screening
- Women of child-bearing potential (that is, women who are not surgically or chemically sterilized and who are between menarche and 1-year postmenopause), test negative for pregnancy at the time of enrollment based on a urine or serum pregnancy test
- Have cardiogenic shock at the time of randomization (systolic blood pressure greater than 90 millimeters of mercury (mm Hg) associated with clinical evidence of end-organ hypoperfusion, or participants requiring vasopressors to maintain systolic blood pressure over 90 mm Hg and associated with clinical evidence of end-organ hypoperfusion
- Have refractory ventricular arrhythmias
- Have New York Heart Association (NYHA) Class IV congestive heart failure
- Have systolic blood pressure greater than 180 mm Hg, or diastolic blood pressure greater than 100 mm Hg on more than 1 assessment at any time from participant presentation of ACS treatment to enrollment
- Have received fibrin-specific fibrinolytic therapy less than 24 hours prior to randomization
- Have received nonfibrin-specific fibrinolytic therapy less than 48 hours prior to randomization
- Have active internal bleeding or history of bleeding diathesis
- Have clinical findings, in the judgment of the investigator, associated with an increased risk of bleeding
- Prior history of ischemic or hemorrhagic stroke
- Intracranial neoplasm, arteriovenous malformation, or aneurysm
- Prior history of transient ischemic attack (TIA)
- Have an International Normalized Ratio (INR) known to be greater than 1.5 at the time of evaluation
- Have a platelet count of less than 100,000 per cubic millimeter (mm^3) at the time of evaluation
- Have anemia [hemoglobin (Hgb) less than 10 grams per deciliter (g/dL)] at the time of evaluation
- Have received 1 or more doses of a thienopyridine (ticlopidine, clopidogrel, or prasugrel) or other adenosine diphosphate (ADP) receptor inhibitor within 10 days prior to screening
- Have been administered glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor within the past 7 days or planned use of a GPIIb/IIIa inhibitor during PCI
- Are receiving or will receive oral anticoagulation or other antiplatelet therapy, other than aspirin (ASA), which cannot be safely discontinued for the duration of the study.
- Are receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX2) inhibitors that cannot be discontinued during the study
- Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
- Have previously completed or withdrawn from this study or any other study investigating prasugrel
- Are women who are known to be pregnant, who have given birth within the past 90 days, or who are breastfeeding
- Have a concomitant medical illness (for example, terminal malignancy) that in the opinion of the investigator, is associated with reduced survival over the expected treatment period
- Have known severe hepatic dysfunction (that is, with cirrhosis or portal hypertension)
- Have a history of intolerance or allergy to aspirin or approved thienopyridines (ticlopidine, clopidogrel or prasugrel)
- May be unable to cooperate with protocol requirements and follow-up procedures
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo and 60 milligram (mg) Prasugrel Prasugrel Placebo loading dose administered once orally before percutaneous coronary intervention (PCI) and 60-mg prasugrel loading dose administered once orally during PCI, followed by 10-mg prasugrel maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours. Placebo and 60 milligram (mg) Prasugrel Placebo Placebo loading dose administered once orally before percutaneous coronary intervention (PCI) and 60-mg prasugrel loading dose administered once orally during PCI, followed by 10-mg prasugrel maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours. 600 mg Clopidogrel and 60 mg Prasugrel Prasugrel 600-mg clopidogrel loading dose administered once orally before PCI and 60-mg prasugrel loading dose administered once orally during PCI, followed by 10-mg prasugrel maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours. 600 mg Clopidogrel and 30 mg Prasugrel Prasugrel 600-mg clopidogrel loading dose administered once orally before PCI and 30-mg prasugrel loading dose administered once orally during PCI, followed by 10-mg prasugrel maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours. 600 mg Clopidogrel and 60 mg Prasugrel Clopidogrel 600-mg clopidogrel loading dose administered once orally before PCI and 60-mg prasugrel loading dose administered once orally during PCI, followed by 10-mg prasugrel maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours. 600 mg Clopidogrel and 30 mg Prasugrel Clopidogrel 600-mg clopidogrel loading dose administered once orally before PCI and 30-mg prasugrel loading dose administered once orally during PCI, followed by 10-mg prasugrel maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours.
- Primary Outcome Measures
Name Time Method Adenosine Diphosphate (ADP)-Induced P2Y12 Receptor-Mediated Platelet Aggregation 6 Hours After Prasugrel Loading Dose (LD) 6 hours after prasugrel loading dose ADP-induced P2Y12 receptor mediated platelet aggregation serves as a biomarker of platelet function. It is measured in P2Y12 Reaction Units (PRU) with lower PRU reflecting stronger inhibition of P2Y12 and reduced platelet aggregation. Least Squares (LS) Mean values were controlled for treatment, visit, treatment and visit interaction, and country.
- Secondary Outcome Measures
Name Time Method Adenosine Diphosphate (ADP)-Induced P2Y12 Receptor-Mediated Platelet Aggregation at Baseline, 2, 24 and 72 Hours After Prasugrel Loading Dose (LD) Baseline and 2 hours and 24 hours and 72 hours after prasugrel loading dose ADP-induced P2Y12 receptor mediated platelet aggregation serves as a biomarker of platelet function. It is measured in P2Y12 Reaction Units (PRU) with lower PRU reflecting stronger inhibition of P2Y12 and reduced platelet aggregation. Least Squares (LS) Mean values were controlled for treatment, visit, treatment and visit interaction, and country.
Mean Change From Baseline to 72 Hours in Laboratory Measurements - Hematocrit Baseline, 72 hours Mean Change From Baseline to 72 Hours in Laboratory Measurements - Hemoglobin Baseline, 72 hours Percentage of Inhibition of Platelet Aggregation Baseline and 2 and 6 and 24 and 72 hours after loading dose Adenosine Diphosphate (ADP)-induced P2Y12 receptor mediated platelet aggregation serves as a biomarker of platelet function. It is measured in P2Y12 Reaction Units (PRU) with lower PRU reflecting stronger inhibition of P2Y12 and reduced platelet aggregation. The internal BASE standard is an independent measurement and serves as an estimate of the participant's baseline platelet aggregation independent of P2Y12 receptor inhibition. Percent Inhibition of Platelet Aggregation=(1-\[PRU/BASE) x 100%, high numbers represent increased platelet inhibition. Least Squares (LS) Mean values were controlled for treatment, visit, treatment and visit interaction, and country.
Percentage of Poor Responders Baseline and 2 and 6 and 24 and 72 hours after loading dose Poor responders are those who had P2Y12 Reaction Units (PRU)≥ 240.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Baseline through 72 hours after prasugrel loading dose TEAE is a worsening or new occurrence of adverse event (AE) during treatment compared to baseline. A summary of serious adverse events (SAE) and other nonserious AE are located in the Reported Adverse Events section.
P2Y12 Reaction Units (PRU) of Clopidogrel Treated Participants at Baseline by Cytochrome P450 2C19 (CYP2C19)-Predicted Functional Groups - CYP2C19 Extensive Metabolizers (EM) and Reduced Metabolizers (RM) Baseline CYP2C19 is a drug metabolizing enzyme. CYP2C19 Extensive metabolizers (EM) are individuals with two fully active / normal function CYP2C19 alleles (\*1/\*1, \*1/\*17). CYP2C19 Reduced metabolizers (RM) are individuals with at least one reduced-function CYP2C19 allele (\*2/\*2, \*1/\*2). Least Squares (LS) Mean values were controlled for CYP2C19 genetic group.
P2Y12 Reaction Units (PRU) at 6 Hours Post-Prasugrel Loading Dose (LD) by Cytochrome P450 2C19 (CYP2C19)-Predicted Functional Groups - Extensive Metabolizers (EM) and Reduced Metabolizers (RM) 6 hours after prasugrel loading dose CYP2C19 is a drug metabolizing enzyme. CYP2C19 Extensive metabolizers (EM) are individuals with two fully active / normal function CYP2C19 alleles (\*1/\*1, \*1/\*17). CYP2C19 Reduced metabolizers (RM) are individuals with at least one reduced-function CYP2C19 allele (\*2/\*2, \*1/\*2). Least Squares (LS) Mean values were controlled for CYP2C19 genetic group.
Trial Locations
- Locations (1)
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
🇮🇳New Delhi, India