Clopidogrel to Prasugrel in Acute Coronary Syndrome (ACS) Patients

Acute Coronary Syndrome Clinical Trial

Official title:

TRansferring From ClopIdogrel Loading Dose to Prasugrel Loading Dose in Acute Coronary Syndrome PatiEnTs: TRIPLET

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01115738
• Other study ID #: 13533
• Secondary ID: H7T-CR-TAEHCTRI/
• Status: Completed
• Phase: Phase 2
• First received: April 23, 2010
• Last updated: November 15, 2012
• Start date: May 2010
• Est. completion date: November 2011

Study information

• Verified date: November 2012
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustralia: Department of Health and Ageing Therapeutic Goods AdministrationBrazil: Ministry of HealthCanada: Health CanadaIndia: Ministry of Science and TechnologyMexico: Federal Commission for Sanitary Risks ProtectionTurkey: Ministry of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 282
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Syndrome

Intervention

Drug:
• Prasugrel
Loading dose administered once orally and maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours.
• Clopidogrel
Loading dose administered once orally.
• Placebo
Loading dose administered once orally

Locations

Country	Name	City	State
India	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.	Bangalore
India	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.	Hyderabaad
India	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

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adenosine Diphosphate (ADP)-Induced P2Y12 Receptor-Mediated Platelet Aggregation 6 Hours After Prasugrel Loading Dose (LD)	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.	6 hours after prasugrel loading dose	No
Secondary	Adenosine Diphosphate (ADP)-Induced P2Y12 Receptor-Mediated Platelet Aggregation at Baseline, 2, 24 and 72 Hours After Prasugrel Loading Dose (LD)	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.	Baseline and 2 hours and 24 hours and 72 hours after prasugrel loading dose	No
Secondary	Mean Change From Baseline to 72 Hours in Laboratory Measurements - Hematocrit		Baseline, 72 hours	Yes
Secondary	Mean Change From Baseline to 72 Hours in Laboratory Measurements - Hemoglobin		Baseline, 72 hours	Yes
Secondary	Percentage of Inhibition of Platelet Aggregation	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.	Baseline and 2 and 6 and 24 and 72 hours after loading dose	No
Secondary	Percentage of Poor Responders	Poor responders are those who had P2Y12 Reaction Units (PRU)= 240.	Baseline and 2 and 6 and 24 and 72 hours after loading dose	No
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs)	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.	Baseline through 72 hours after prasugrel loading dose	Yes
Secondary	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)	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.	Baseline	No
Secondary	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)	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.	6 hours after prasugrel loading dose	No