ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effect on Blood Cells, Known as Platelets, Using Prasugrel vs Clopidogrel in Patients With the Heart Problem Acute Coronary Syndrome (ACS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00385944
Recruitment Status : Completed
First Posted : October 11, 2006
Results First Posted : September 16, 2010
Last Update Posted : September 16, 2010
Sponsor:
Collaborator:
Daiichi Sankyo, Inc.
Information provided by:
Eli Lilly and Company

Brief Summary:
This is a multicenter, randomized, double-blind, cross-over study to compare the pharmacodynamic response in subjects with Acute Coronary Syndrome receiving a 10-mg maintenance dose (MD) of prasugrel compared with a 150-mg maintenance dose of clopidogrel, following a 900-mg loading dose (LD) of clopidogrel.

Condition or disease Intervention/treatment Phase
Acute Coronary Syndrome Drug: Prasugrel Drug: Clopidogrel Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blind Cross-Over Study Comparing the Pharmacodynamic (PD)Response in Subjects With ACS Receiving 14 Days 10-mg Maintenance Dose (MD) Prasugrel vs 14 Days 150-mg MD Clopidogrel After Using a 900-mg Loading Dose (LD) of Clopidogrel to Reduce Ongoing Platelet Activation
Study Start Date : March 2007
Actual Primary Completion Date : October 2007
Actual Study Completion Date : October 2007

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Prasugrel
Open label lead-in one time dose of Clopidogrel 900 mg oral tablets (a single or cumulative dose) and 250 mg to 500 mg aspirin loading dose (LD), either orally or intravenously. Patients are then assigned to maintenance dose (MD) prasugrel 10 mg and two placebo tablets, matched to clopidogrel, and 100 mg aspirin, all taken orally once a day for 14 days. Patients cross-over to MD of clopidogrel two 75 mg tablets and one placebo matched to prasugrel and 100 mg aspirin, all taken orally once a day for the next 14 days.
Drug: Prasugrel
Prasugrel 10-mg tablet taken orally as a daily maintenance dose for a 14-day treatment period.
Other Names:
  • LY640315
  • Effient
  • Efient

Active Comparator: Clopidogrel
Open label lead-in one time dose of Clopidogrel 900 mg oral tablets (a single or cumulative dose) and 250 mg to 500 mg aspirin loading dose (LD), either orally or intravenously. Patients are then assigned to maintenance dose (MD) Clopidogrel two 75 mg and one placebo tablet, matched to prasugrel, and 100 mg aspirin, all taken orally once a day for 14 days. Patients cross-over to MD of prasugrel one 10 mg tablet and two placebo tablets matched to clopidogrel and 100 mg aspirin, all taken orally once a day for the next 14 days.
Drug: Clopidogrel
Clopidogrel two 75-mg tablets taken orally as a daily maintenance dose for a 14-day treatment period.




Primary Outcome Measures :
  1. Maximum Platelet Aggregation (MPA) to 20 Micromolar (μM) Adenosine Diphosphate (ADP) [ Time Frame: 14 days after maintenance dose (MD) ]
    Maximum platelet aggregation (MPA) to 20 μM adenosine diphosphate (ADP) was assessed by light transmission aggregometry (LTA).


Secondary Outcome Measures :
  1. MPA to 5 μM ADP [ Time Frame: 14 days after maintenance dose (MD) ]
    Maximum platelet aggregation to 5 μM ADP was assessed by LTA.

  2. Mean Residual Platelet Aggregation (RPA) to 20 µM ADP [ Time Frame: 14 days after maintenance dose (MD) ]
    Residual platelet aggregation is the percentage (%) aggregation value as measured by LTA at 6 minutes after the addition of ADP.

  3. Mean Residual Platelet Aggregation (RPA) to 5 µM ADP [ Time Frame: 14 days after maintenance dose (MD) ]
    Residual platelet aggregation is the percentage (%) aggregation value as measured by LTA at 6 minutes after the addition of ADP.

  4. Inhibition Platelet Aggregation (IPA) to 20 μM ADP [ Time Frame: 14 days after maintenance dose (MD) ]

    IPA is calculated as a percent decrease of MPA from baseline using the following formula:

    ([MPA at baseline - MPA at time of postbaseline] / MPA at baseline) x 100%


  5. Inhibition Platelet Aggregation (IPA) to 5 μM ADP [ Time Frame: 14 days after maintenance dose (MD) ]

    IPA is calculated as a percent decrease of MPA from baseline using the following formula:

    ([MPA at baseline - MPA at time of postbaseline] / MPA at baseline) x 100%


  6. Inhibition of Residual Platelet Aggregation (IRPA) to 20 μM ADP [ Time Frame: 14 days after maintenance dose (MD) ]

    IRPA is calculated as a percent decrease of RPA from baseline using the following formula:

    ([RPA at baseline - RPA at time of postbaseline] / RPA at baseline) x 100%


  7. Inhibition of Residual Platelet Aggregation (IRPA) to 5 μM ADP [ Time Frame: 14 days after maintenance dose (MD) ]

    IRPA is calculated as a percent decrease of RPA from baseline using the following formula:

    ([RPA at baseline - RPA at time of postbaseline] / RPA at baseline) x 100%


  8. Platelet Reactivity Index (PRI) [ Time Frame: 14 days after maintenance dose (MD) ]

    Platelet Reactivity Index percentage was assessed by Vasodilator-stimulated phosphoprotein (VASP). PRI percent (%) was calculated using the median fluorescence intensity (MFI) of samples included with prostaglandin E1 (PGE1) and ADP, according to the following formula:

    PRI%=[(MFI(PGE1)-MFI(PGE1 + ADP)/MFI(PGE1)]x100

    Lower PRI% values indicate greater P2Y12 receptor blockade.


  9. P2Y12 Reaction Units (PRU) [ Time Frame: 14 days after maintenance dose (MD) ]
    P2Y12 Reaction Units (PRU) assessed by Accumetrics Verify NowTM P2Y12. PRU represents the rate and extent of adenosine (ADP)-stimulated platelet aggregation. Lower values indicate greater P2Y12 platelet inhibition.

  10. Poor Responder of MPA to 20 μM ADP Following Maintenance Dose (MD) [ Time Frame: 14 days after maintenance dose (MD) ]
    Poor responder is defined as MPA to 20 μM ADP >75th percentile of the value at 6-18 hours post-clopidogrel LD.

  11. Change in MPA to 20 μM ADP From Baseline to 6-18 Hrs Post Loading Dose (LD) [ Time Frame: Baseline to 6-18 hrs post loading dose (LD) ]
    Maximum platelet aggregation to 20 μM ADP was assessed by LTA.

  12. Change in MPA to 20 μM ADP From 6-18 Hrs Post Loading Dose (LD) to 14 Days After the First Maintenance Dose (MD) [ Time Frame: 6-18 hrs post loading dose (LD) to 14 days after the first maintenance dose (MD) ]
    Maximum platelet aggregation to 20 μM ADP was assessed by LTA.

  13. MPA to 20 μM ADP at 14 Days After the First Maintenance Dose (MD) [ Time Frame: 14 days after the first maintenance dose (MD) ]
    Maximum platelet aggregation to 20 μM ADP was assessed by LTA.

  14. MPA to 20 μM ADP at 14 Days After the Second Maintenance Dose (MD) [ Time Frame: 14 days after the second maintenance dose (MD) ]
    Maximum platelet aggregation to 20 μM ADP was assessed by LTA.

  15. Number of Participants With Bleeding Events According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria [ Time Frame: 14 days after maintenance dose (MD) ]
    Bleeding events will be classified as Major Bleeding, Minor Bleeding, or Insignificant Bleeding according to the TIMI criteria. 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 gm/dL from baseline. Minor Bleeding: any clinically overt bleeding associated with a fall in Hgb of ≥3 grams/deciliter (gm/dL) but <5 gm/dL from baseline. Insignificant bleeding: any bleeding event that does not meet criteria for a Major or Minor bleed.

  16. Number of Participants With Bleeding Events According to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) [ Time Frame: 14 days after maintenance dose (MD) ]
    Bleeding events will be classified according to the GUSTO definitions as follows: Severe or Life-Threatening Bleeding: any ICH OR any bleeding event resulting in substantial hemodynamic compromise requiring treatment. Moderate Bleeding: any bleeding event resulting in the need for transfusion. Minor bleeding: any other bleeding event that does not require transfusion or cause hemodynamic compromise.

  17. Correlation of MPA to 20 μM ADP and PRU [ Time Frame: Baseline through 29 days of treatment ]
    Pearson-correlation estimated between MPA to 20 μM ADP and Accumetrics VerifyNowTM P2Y12 PRU



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Present with acute coronary syndrome (ACS) and have planned treatment with a one-time 900-mg loading dose of commercially available clopidogrel (administered as a single or cumulative dose).
  • Are between the ages of 18 and 85 years.
  • Willing and able to sign informed consent.

Exclusion Criteria:

  • Have overt ST-segment elevation myocardial infarction (STEMI).
  • Have cardiogenic shock.
  • Have refractory ventricular arrhythmias.
  • Have New York Heart Association (NYHA) Class IV congestive heart failure.
  • Have severe and uncontrolled hypertension.
  • Have active internal bleeding or history of bleeding diathesis.
  • Have an increased risk of bleeding.
  • Have history of cerebrovascular accidents.
  • Have certain abnormal blood level values.
  • Are currently receiving chemotherapy or radiation therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00385944


Locations
France
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.
Creteil, France, 94010
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.
Paris, France, 75013
Sponsors and Collaborators
Eli Lilly and Company
Daiichi Sankyo, Inc.
Investigators
Study Director: 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

Additional Information:
Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00385944     History of Changes
Other Study ID Numbers: 10632
H7T-MC-TABN ( Other Identifier: Eli Lilly and Company )
First Posted: October 11, 2006    Key Record Dates
Results First Posted: September 16, 2010
Last Update Posted: September 16, 2010
Last Verified: August 2010

Additional relevant MeSH terms:
Syndrome
Acute Coronary Syndrome
Disease
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Clopidogrel
Ticlopidine
Prasugrel Hydrochloride
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors