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

Phase 2

Completed

Conditions: Acute Coronary Syndrome

Interventions: Drug: Prasugrel
Drug: Clopidogrel

Registration Number: NCT00385944

Lead Sponsor: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 56

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Prasugrel	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.
Clopidogrel	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.

Primary Outcome Measures

Name	Time	Method
Maximum Platelet Aggregation (MPA) to 20 Micromolar (μM) Adenosine Diphosphate (ADP)	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

Name	Time	Method
MPA to 5 μM ADP	14 days after maintenance dose (MD)	Maximum platelet aggregation to 5 μM ADP was assessed by LTA.
Mean Residual Platelet Aggregation (RPA) to 20 µM ADP	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.
Mean Residual Platelet Aggregation (RPA) to 5 µM ADP	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.
Inhibition Platelet Aggregation (IPA) to 20 μM ADP	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%
Inhibition Platelet Aggregation (IPA) to 5 μM ADP	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%
Inhibition of Residual Platelet Aggregation (IRPA) to 20 μM ADP	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%
Inhibition of Residual Platelet Aggregation (IRPA) to 5 μM ADP	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%
Platelet Reactivity Index (PRI)	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.
P2Y12 Reaction Units (PRU)	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.
Poor Responder of MPA to 20 μM ADP Following Maintenance Dose (MD)	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.
Change in MPA to 20 μM ADP From Baseline to 6-18 Hrs Post Loading Dose (LD)	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)	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)	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)	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	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.
Number of Participants With Bleeding Events According to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO)	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.
Correlation of MPA to 20 μM ADP and PRU	Baseline through 29 days of treatment	Pearson-correlation estimated between MPA to 20 μM ADP and Accumetrics VerifyNowTM P2Y12 PRU

Trial Locations

Locations (1): 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.
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