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

Primary Purpose

Acute Coronary Syndrome

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Prasugrel
Clopidogrel
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Coronary Syndrome

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • 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.
  • 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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Prasugrel

Clopidogrel

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Maximum Platelet Aggregation (MPA) to 20 Micromolar (μM) Adenosine Diphosphate (ADP)
Maximum platelet aggregation (MPA) to 20 μM adenosine diphosphate (ADP) was assessed by light transmission aggregometry (LTA).

Secondary Outcome Measures

MPA to 5 μM ADP
Maximum platelet aggregation to 5 μM ADP was assessed by LTA.
Mean Residual Platelet Aggregation (RPA) to 20 µM ADP
Residual platelet aggregation is the percentage (%) aggregation value as measured by LTA at 6 minutes after the addition of ADP.
Mean Residual Platelet Aggregation (RPA) to 5 µM ADP
Residual platelet aggregation is the percentage (%) aggregation value as measured by LTA at 6 minutes after the addition of ADP.
Inhibition Platelet Aggregation (IPA) to 20 μM ADP
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%
Inhibition Platelet Aggregation (IPA) to 5 μM ADP
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%
Inhibition of Residual Platelet Aggregation (IRPA) to 20 μM ADP
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%
Inhibition of Residual Platelet Aggregation (IRPA) to 5 μM ADP
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%
Platelet Reactivity Index (PRI)
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.
P2Y12 Reaction Units (PRU)
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.
Poor Responder of MPA to 20 μM ADP Following 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.
Change in MPA to 20 μM ADP From Baseline to 6-18 Hrs Post Loading Dose (LD)
Maximum platelet aggregation to 20 μM ADP was assessed by LTA.
Change in MPA to 20 μM ADP From 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.
MPA to 20 μM ADP at 14 Days After the First Maintenance Dose (MD)
Maximum platelet aggregation to 20 μM ADP was assessed by LTA.
MPA to 20 μM ADP at 14 Days After the Second Maintenance Dose (MD)
Maximum platelet aggregation to 20 μM ADP was assessed by LTA.
Number of Participants With Bleeding Events According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria
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.
Number of Participants With Bleeding Events According to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO)
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.
Correlation of MPA to 20 μM ADP and PRU
Pearson-correlation estimated between MPA to 20 μM ADP and Accumetrics VerifyNowTM P2Y12 PRU

Full Information

First Posted
October 6, 2006
Last Updated
August 25, 2010
Sponsor
Eli Lilly and Company
Collaborators
Daiichi Sankyo, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00385944
Brief Title
The Effect on Blood Cells, Known as Platelets, Using Prasugrel vs Clopidogrel in Patients With the Heart Problem Acute Coronary Syndrome (ACS)
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 Type
Interventional

2. Study Status

Record Verification Date
August 2010
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
October 2007 (Actual)
Study Completion Date
October 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Eli Lilly and Company
Collaborators
Daiichi Sankyo, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Coronary Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prasugrel
Arm Type
Experimental
Arm Description
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.
Arm Title
Clopidogrel
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Prasugrel
Other Intervention Name(s)
LY640315, Effient, Efient
Intervention Description
Prasugrel 10-mg tablet taken orally as a daily maintenance dose for a 14-day treatment period.
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Intervention Description
Clopidogrel two 75-mg tablets taken orally as a daily maintenance dose for a 14-day treatment period.
Primary Outcome Measure Information:
Title
Maximum Platelet Aggregation (MPA) to 20 Micromolar (μM) Adenosine Diphosphate (ADP)
Description
Maximum platelet aggregation (MPA) to 20 μM adenosine diphosphate (ADP) was assessed by light transmission aggregometry (LTA).
Time Frame
14 days after maintenance dose (MD)
Secondary Outcome Measure Information:
Title
MPA to 5 μM ADP
Description
Maximum platelet aggregation to 5 μM ADP was assessed by LTA.
Time Frame
14 days after maintenance dose (MD)
Title
Mean Residual Platelet Aggregation (RPA) to 20 µM ADP
Description
Residual platelet aggregation is the percentage (%) aggregation value as measured by LTA at 6 minutes after the addition of ADP.
Time Frame
14 days after maintenance dose (MD)
Title
Mean Residual Platelet Aggregation (RPA) to 5 µM ADP
Description
Residual platelet aggregation is the percentage (%) aggregation value as measured by LTA at 6 minutes after the addition of ADP.
Time Frame
14 days after maintenance dose (MD)
Title
Inhibition Platelet Aggregation (IPA) to 20 μM ADP
Description
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%
Time Frame
14 days after maintenance dose (MD)
Title
Inhibition Platelet Aggregation (IPA) to 5 μM ADP
Description
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%
Time Frame
14 days after maintenance dose (MD)
Title
Inhibition of Residual Platelet Aggregation (IRPA) to 20 μM ADP
Description
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%
Time Frame
14 days after maintenance dose (MD)
Title
Inhibition of Residual Platelet Aggregation (IRPA) to 5 μM ADP
Description
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%
Time Frame
14 days after maintenance dose (MD)
Title
Platelet Reactivity Index (PRI)
Description
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.
Time Frame
14 days after maintenance dose (MD)
Title
P2Y12 Reaction Units (PRU)
Description
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.
Time Frame
14 days after maintenance dose (MD)
Title
Poor Responder of MPA to 20 μM ADP Following Maintenance Dose (MD)
Description
Poor responder is defined as MPA to 20 μM ADP >75th percentile of the value at 6-18 hours post-clopidogrel LD.
Time Frame
14 days after maintenance dose (MD)
Title
Change in MPA to 20 μM ADP From Baseline to 6-18 Hrs Post Loading Dose (LD)
Description
Maximum platelet aggregation to 20 μM ADP was assessed by LTA.
Time Frame
Baseline to 6-18 hrs post loading dose (LD)
Title
Change in MPA to 20 μM ADP From 6-18 Hrs Post Loading Dose (LD) to 14 Days After the First Maintenance Dose (MD)
Description
Maximum platelet aggregation to 20 μM ADP was assessed by LTA.
Time Frame
6-18 hrs post loading dose (LD) to 14 days after the first maintenance dose (MD)
Title
MPA to 20 μM ADP at 14 Days After the First Maintenance Dose (MD)
Description
Maximum platelet aggregation to 20 μM ADP was assessed by LTA.
Time Frame
14 days after the first maintenance dose (MD)
Title
MPA to 20 μM ADP at 14 Days After the Second Maintenance Dose (MD)
Description
Maximum platelet aggregation to 20 μM ADP was assessed by LTA.
Time Frame
14 days after the second maintenance dose (MD)
Title
Number of Participants With Bleeding Events According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria
Description
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.
Time Frame
14 days after maintenance dose (MD)
Title
Number of Participants With Bleeding Events According to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO)
Description
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.
Time Frame
14 days after maintenance dose (MD)
Title
Correlation of MPA to 20 μM ADP and PRU
Description
Pearson-correlation estimated between MPA to 20 μM ADP and Accumetrics VerifyNowTM P2Y12 PRU
Time Frame
Baseline through 29 days of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
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.
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
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.
City
Paris
ZIP/Postal Code
75013
Country
France

12. IPD Sharing Statement

Learn more about this trial

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

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