Clopidogrel to Prasugrel in Acute Coronary Syndrome (ACS) Patients

NCT01115738 | Completed Phase 2 Results

• 3 other identifiers: 13533H7T-CR-TAEHCTRI/2010/091/000348
• Study Type: interventional
• Target: 282
• Locations: 1 country
• Sites: 3

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.

Conditions

Acute Coronary Syndrome

Keywords

Plavix, Effient

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (8)

• 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

• 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

• Percentage of Poor Responders

  Baseline and 2 and 6 and 24 and 72 hours after loading dose

Study Arms (3)

Placebo and 60 milligram (mg) Prasugrel

PLACEBO COMPARATOR

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.

Drug: Prasugrel; Drug: Placebo

600 mg Clopidogrel and 60 mg Prasugrel

EXPERIMENTAL

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.

Drug: Prasugrel; Drug: Clopidogrel

600 mg Clopidogrel and 30 mg Prasugrel

EXPERIMENTAL

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.

Drug: Prasugrel; Drug: Clopidogrel

Interventions

Prasugrel DRUG

Loading dose administered once orally and maintenance dose administered orally 24 hours after loading dose, then every 24 hours for 72 hours.

Also known as: LY640315

600 mg Clopidogrel and 30 mg Prasugrel; 600 mg Clopidogrel and 60 mg Prasugrel; Placebo and 60 milligram (mg) Prasugrel

Clopidogrel DRUG

Loading dose administered once orally.

600 mg Clopidogrel and 30 mg Prasugrel; 600 mg Clopidogrel and 60 mg Prasugrel

Placebo DRUG

Loading dose administered once orally

Placebo and 60 milligram (mg) Prasugrel

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (3)

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, 560099, India

Location

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, 500 001, India

Location

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, 110 060, India

Location

Related Publications (2)

• Diodati JG, Saucedo JF, Cardillo TE, Jakubowski JA, Henneges C, Effron MB, Lipkin FR, Walker JR, Duvvuru S, Sundseth SS, Fisher HN, Angiolillo DJ. Transferring from clopidogrel loading dose to prasugrel loading dose in acute coronary syndrome patients. High on-treatment platelet reactivity analysis of the TRIPLET trial. Thromb Haemost. 2014 Aug;112(2):311-22. doi: 10.1160/TH13-09-0747. Epub 2014 Apr 10.

  PMID: 24718367 DERIVED

• Diodati JG, Saucedo JF, French JK, Fung AY, Cardillo TE, Henneges C, Effron MB, Fisher HN, Angiolillo DJ. Effect on platelet reactivity from a prasugrel loading dose after a clopidogrel loading dose compared with a prasugrel loading dose alone: Transferring From Clopidogrel Loading Dose to Prasugrel Loading Dose in Acute Coronary Syndrome Patients (TRIPLET): a randomized controlled trial. Circ Cardiovasc Interv. 2013 Oct 1;6(5):567-74. doi: 10.1161/CIRCINTERVENTIONS.112.000063. Epub 2013 Sep 24.

  PMID: 24065443 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Prasugrel Hydrochloride; Clopidogrel

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ticlopidine; Thienopyridines; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2010
• First Posted: May 4, 2010
• Study Start: May 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: November 20, 2012
• Results First Posted: October 26, 2012

Record last verified: 2012-11

Locations

IN (3)