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

Acute Coronary Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00385944
• Other study ID #: 10632
• Secondary ID: H7T-MC-TABN
• Status: Completed
• Phase: Phase 2
• First received: October 6, 2006
• Last updated: August 25, 2010
• Start date: March 2007
• Est. completion date: October 2007

Study information

• Verified date: August 2010
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: October 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome

Intervention

Drug:
• Prasugrel
Prasugrel 10-mg tablet taken orally as a daily maintenance dose for a 14-day treatment period.
• Clopidogrel
Clopidogrel two 75-mg tablets taken orally as a daily maintenance dose for a 14-day treatment period.

Locations

Country	Name	City	State
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	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

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Daiichi Sankyo Inc.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	14 days after maintenance dose (MD)	No
Secondary	MPA to 5 µM ADP	Maximum platelet aggregation to 5 µM ADP was assessed by LTA.	14 days after maintenance dose (MD)	No
Secondary	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.	14 days after maintenance dose (MD)	No
Secondary	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.	14 days after maintenance dose (MD)	No
Secondary	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%	14 days after maintenance dose (MD)	No
Secondary	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%	14 days after maintenance dose (MD)	No
Secondary	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%	14 days after maintenance dose (MD)	No
Secondary	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%	14 days after maintenance dose (MD)	No
Secondary	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.	14 days after maintenance dose (MD)	No
Secondary	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.	14 days after maintenance dose (MD)	No
Secondary	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.	14 days after maintenance dose (MD)	No
Secondary	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.	Baseline to 6-18 hrs post loading dose (LD)	No
Secondary	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.	6-18 hrs post loading dose (LD) to 14 days after the first maintenance dose (MD)	No
Secondary	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.	14 days after the first maintenance dose (MD)	No
Secondary	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.	14 days after the second maintenance dose (MD)	No
Secondary	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.	14 days after maintenance dose (MD)	Yes
Secondary	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.	14 days after maintenance dose (MD)	Yes
Secondary	Correlation of MPA to 20 µM ADP and PRU	Pearson-correlation estimated between MPA to 20 µM ADP and Accumetrics VerifyNowTM P2Y12 PRU	Baseline through 29 days of treatment	No

External Links

•   Lilly Clinical Trial Registry