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

Sponsor:	Eli Lilly and Company
Collaborator:	Daiichi Sankyo Inc.
Information provided by:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00385944

Purpose

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	Intervention	Phase
Acute Coronary Syndrome	Drug: Prasugrel Drug: Clopidogrel	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

Drug Information available for: Clopidogrel Clopidogrel Bisulfate Prasugrel

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Maximum Platelet Aggregation (MPA) to 20 Micromolar (μM) Adenosine Diphosphate (ADP) [ Time Frame: 14 days after maintenance dose (MD) ] [ Designated as safety issue: No ]
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 [ Time Frame: 14 days after maintenance dose (MD) ] [ Designated as safety issue: No ]
Maximum platelet aggregation to 5 μM ADP was assessed by LTA.
Mean Residual Platelet Aggregation (RPA) to 20 µM ADP [ Time Frame: 14 days after maintenance dose (MD) ] [ Designated as safety issue: No ]
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 [ Time Frame: 14 days after maintenance dose (MD) ] [ Designated as safety issue: No ]
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 [ Time Frame: 14 days after maintenance dose (MD) ] [ Designated as safety issue: No ]
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 [ Time Frame: 14 days after maintenance dose (MD) ] [ Designated as safety issue: No ]
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 [ Time Frame: 14 days after maintenance dose (MD) ] [ Designated as safety issue: No ]
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 [ Time Frame: 14 days after maintenance dose (MD) ] [ Designated as safety issue: No ]
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) [ Time Frame: 14 days after maintenance dose (MD) ] [ Designated as safety issue: No ]
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) [ Time Frame: 14 days after maintenance dose (MD) ] [ Designated as safety issue: No ]
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) [ Time Frame: 14 days after maintenance dose (MD) ] [ Designated as safety issue: No ]
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) [ Time Frame: Baseline to 6-18 hrs post loading dose (LD) ] [ Designated as safety issue: No ]
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) [ Time Frame: 6-18 hrs post loading dose (LD) to 14 days after the first maintenance dose (MD) ] [ Designated as safety issue: No ]
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) [ Time Frame: 14 days after the first maintenance dose (MD) ] [ Designated as safety issue: No ]
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) [ Time Frame: 14 days after the second maintenance dose (MD) ] [ Designated as safety issue: No ]
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 [ Time Frame: 14 days after maintenance dose (MD) ] [ Designated as safety issue: Yes ]
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) [ Time Frame: 14 days after maintenance dose (MD) ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Baseline through 29 days of treatment ] [ Designated as safety issue: No ]
Pearson-correlation estimated between MPA to 20 μM ADP and Accumetrics VerifyNowTM P2Y12 PRU

Enrollment:	56
Study Start Date:	March 2007
Study Completion Date:	October 2007
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: 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

More Information

Additional Information:

Lilly Clinical Trial Registry This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier:	NCT00385944 History of Changes
Other Study ID Numbers:	10632, H7T-MC-TABN
Study First Received:	October 6, 2006
Results First Received:	April 19, 2010
Last Updated:	August 25, 2010
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Clopidogrel
Ticlopidine
Prasugrel
Platelet Aggregation Inhibitors

Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
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
Cardiovascular Agents

ClinicalTrials.gov processed this record on February 09, 2012