Back to resultsStudy to Learn When Platelets Return to Normal After One Loading Dose of Anti-platelet Drugs in Patients With Symptoms of Acute Coronary Syndromes
Primary Purpose
Acute Coronary Syndromes
Status
Terminated
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
clopidogrel
prasugrel
Sponsored by
About this trial
This is an interventional treatment trial for Acute Coronary Syndromes focused on measuring Acute Coronary Syndromes, Angina, Platelet Function, Coronary Angiography, Clinical Symptoms of Angina, Positive Stress Test
Eligibility Criteria
Inclusion Criteria:
- Men or women ≥18 to <80 years of age who present with any one of the following:
- symptoms of Acute Coronary Syndromes (ACS)
- clinical symptoms of angina, or a positive stress test or who return for routine follow up angiography post stent placement in whom co-administration of aspirin and a thienopyridine (that is, clopidogrel, ticlopidine, or prasugrel) is not contraindicated
Exclusion Criteria:
- Those presenting with ST-elevation MI (STEMI)
- histories of refractory ventricular arrhythmias
- an implanted defibrillator device
- congestive heart failure (NYHA Class III or above) within 6 months prior to screening
- significant hypertension
- subjects with a history or clinical suspicion of cerebral vascular malformations, transient ischaemic attack, or stroke
- bleeding disorders
- women known to be pregnant, who have given birth within the past 90 days, or who are breastfeeding
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.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Experimental
Arm Label
clopidogrel 600 mg
prasugrel 60 mg
prasugrel 30 mg
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Participants Returning to Baseline Platelet Function
Participants were classified as having platelet function return to baseline after loading dose (LD) on the first day that P2Y12 Reaction Units (PRU) was no more than 60 PRU below baseline and remained in this range. PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of adenosine diphosphate (ADP)-stimulated platelet aggregation.
Secondary Outcome Measures
The Day on Which 50%, 75% and 90% of Subjects Return to Baseline Platelet Function Following a Single LD of 30-mg or 60-mg Prasugrel or 600-mg Clopidogrel
This outcome measure was not analyzed due to the limited sample size.
The Day When the Proportion of Participants Who Return to Baseline Platelet Function in the 30-mg and 60-mg Prasugrel Groups is Similar to the 600-mg Clopidogrel Group at Day 5 and Day 7
The day at which the proportion of participants who return to baseline platelet P2Y12 receptor function in the prasugrel 30 mg and 60 mg LD groups is similar (within 10% absolute difference) to the proportion of subjects who return to baseline platelet P2Y12 receptor function at day 5 and day 7 in the clopidogrel 600 mg LD group, obtained from Kaplan Meier curves for the primary washout population, was to be presented. This outcome measure was not analyzed due to the limited sample size.
Number of Days to the Return of Baseline Platelet Function Following One Loading Dose (LD)
The return of baseline platelet function following one LD of prasugrel (30 mg or 60 mg) or 600 mg LD of clopidogrel assessed by Verify Now™ P2Y12 Reaction Units (VN-PRU). This outcome measure was not analyzed because it was not appropriate to estimate the days based on the non-inferiority approach due to the limited sample size.
Effect of Initial Inhibition of Platelet Aggregation on the Day to Return to Baseline Platelet Function: VN-PRU
To show effect of initial inhibition of platelet aggregation as measured by Accumetrics Verify Now™ P2Y12 on the day to return to baseline platelet function, a regression model was fitted with day to return as outcome variable and initial inhibition as fixed effect. Results are reported as the predicted day to return to baseline platelet function by derived VN-PRU percent (%) inhibition at 24 hours post LD. The derived VN-PRU % inhibition is calculated as a percent decrease of PRU from baseline using the following formula: ([PRU at baseline - PRU at 24 hours post LD]/PRU at baseline) x 100%.
Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hrs Post-LD) by VN-PRU
PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of adenosine diphosphate (ADP)-stimulated platelet aggregation. This outcome measure was not analyzed due to the limited sample size.
Platelet Function 24 Hours Post Loading Dose
PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of ADP-stimulated platelet aggregation.
Percentage of Poor Pharmacodynamic Responders by Platelet Aggregation at 24 Hours Post-LD
Platelet aggregation was assessed by Accumetrics Verify Now™ P2Y12, and poor responders were those with PRU greater than or equal to 230.
Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA)
Initial inhibition of platelet aggregation was measured by LTA at 5 and 20 μM ADP. Maximum platelet aggregation (MPA) is reported by day.
Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS)
Return of baseline platelet function was assessed by Multiplate® ADP test and ADP test High Sensitivity (HS). Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. The agonist ADP was added to stirred whole blood after dilution (1:2 with 0.9% NaCl solution) in a final concentration of 6.4 µM (ADP Test) or in final concentration of 6.4 µM ADP plus 9.4 nM Prostaglandin E1 (PGE1) (ADPtest HS). Platelet aggregation was continuously recorded for 5 minutes and quantified as area under the aggregation curve (AUC=AU*min) of aggregation units (AU).
Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hours Post-LD) by LTA (5 and 20 μM ADP)
Maximum platelet aggregation (MPA) to 5 and 20 μM ADP were assessed by LTA. This outcome measure was not analyzed due to limited sample size.
Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hrs Post-LD) by Multiplate® ADP Test and ADP Test High Sensitivity (HS)
The Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. After adding 6.4 µM ADP (ADP test) or 6.4 µM ADP plus 9.4 nM Prostaglandin E1 (PGE1) (ADP test HS), area under the aggregation curve (AUC) was calculated. This outcome measure was not analyzed due to limited sample size.
Platelet Function by LTA at 5 and 20 μM ADP
MPA to 5 and 20 μM ADP were assessed by LTA.
Platelet Function by Multiplate® ADP Test and ADP Test HS
The Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. After adding 6.4 µM ADP (ADP test) or 6.4 µM ADP plus 9.4 nM PGE1 (ADP test HS), area under the aggregation curve (AUC) were calculated.
Full Information
NCT ID
NCT01107899
First Posted
April 19, 2010
Last Updated
March 7, 2012
Sponsor
Eli Lilly and Company
Collaborators
Daiichi Sankyo Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT01107899
Brief Title
Study to Learn When Platelets Return to Normal After One Loading Dose of Anti-platelet Drugs in Patients With Symptoms of Acute Coronary Syndromes
Official Title
Recovery of Platelet Function After a Loading Dose of Prasugrel or Clopidogrel in Aspirin-Treated Subjects Presenting With Symptoms of Acute Coronary Syndromes
Study Type
Interventional
2. Study Status
Record Verification Date
March 2012
Overall Recruitment Status
Terminated
Why Stopped
Terminated due to Enrollment futility
Study Start Date
October 2009 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
December 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
Collaborators
Daiichi Sankyo Co., Ltd.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To investigate how platelets recover to normal function in subjects who have symptoms of a heart attack or unstable angina and who get a loading dose of prasugrel or clopidogrel for planned coronary angiography.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Coronary Syndromes
Keywords
Acute Coronary Syndromes, Angina, Platelet Function, Coronary Angiography, Clinical Symptoms of Angina, Positive Stress Test
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
clopidogrel 600 mg
Arm Type
Active Comparator
Arm Title
prasugrel 60 mg
Arm Type
Active Comparator
Arm Title
prasugrel 30 mg
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
clopidogrel
Intervention Description
taken orally, day one, single dose
Intervention Type
Drug
Intervention Name(s)
prasugrel
Other Intervention Name(s)
Efient®, Effient®, LY640315, CS747
Intervention Description
taken orally, day one, single dose
Primary Outcome Measure Information:
Title
Percentage of Participants Returning to Baseline Platelet Function
Description
Participants were classified as having platelet function return to baseline after loading dose (LD) on the first day that P2Y12 Reaction Units (PRU) was no more than 60 PRU below baseline and remained in this range. PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of adenosine diphosphate (ADP)-stimulated platelet aggregation.
Time Frame
Days 3, 5, 7, 9, and 11
Secondary Outcome Measure Information:
Title
The Day on Which 50%, 75% and 90% of Subjects Return to Baseline Platelet Function Following a Single LD of 30-mg or 60-mg Prasugrel or 600-mg Clopidogrel
Description
This outcome measure was not analyzed due to the limited sample size.
Time Frame
Up through 11 days
Title
The Day When the Proportion of Participants Who Return to Baseline Platelet Function in the 30-mg and 60-mg Prasugrel Groups is Similar to the 600-mg Clopidogrel Group at Day 5 and Day 7
Description
The day at which the proportion of participants who return to baseline platelet P2Y12 receptor function in the prasugrel 30 mg and 60 mg LD groups is similar (within 10% absolute difference) to the proportion of subjects who return to baseline platelet P2Y12 receptor function at day 5 and day 7 in the clopidogrel 600 mg LD group, obtained from Kaplan Meier curves for the primary washout population, was to be presented. This outcome measure was not analyzed due to the limited sample size.
Time Frame
Up through 11 days
Title
Number of Days to the Return of Baseline Platelet Function Following One Loading Dose (LD)
Description
The return of baseline platelet function following one LD of prasugrel (30 mg or 60 mg) or 600 mg LD of clopidogrel assessed by Verify Now™ P2Y12 Reaction Units (VN-PRU). This outcome measure was not analyzed because it was not appropriate to estimate the days based on the non-inferiority approach due to the limited sample size.
Time Frame
Up through 11 days
Title
Effect of Initial Inhibition of Platelet Aggregation on the Day to Return to Baseline Platelet Function: VN-PRU
Description
To show effect of initial inhibition of platelet aggregation as measured by Accumetrics Verify Now™ P2Y12 on the day to return to baseline platelet function, a regression model was fitted with day to return as outcome variable and initial inhibition as fixed effect. Results are reported as the predicted day to return to baseline platelet function by derived VN-PRU percent (%) inhibition at 24 hours post LD. The derived VN-PRU % inhibition is calculated as a percent decrease of PRU from baseline using the following formula: ([PRU at baseline - PRU at 24 hours post LD]/PRU at baseline) x 100%.
Time Frame
Up through 11 days
Title
Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hrs Post-LD) by VN-PRU
Description
PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of adenosine diphosphate (ADP)-stimulated platelet aggregation. This outcome measure was not analyzed due to the limited sample size.
Time Frame
Up through 11 days
Title
Platelet Function 24 Hours Post Loading Dose
Description
PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of ADP-stimulated platelet aggregation.
Time Frame
24 hours post-loading dose
Title
Percentage of Poor Pharmacodynamic Responders by Platelet Aggregation at 24 Hours Post-LD
Description
Platelet aggregation was assessed by Accumetrics Verify Now™ P2Y12, and poor responders were those with PRU greater than or equal to 230.
Time Frame
24 hours post-loading dose
Title
Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA)
Description
Initial inhibition of platelet aggregation was measured by LTA at 5 and 20 μM ADP. Maximum platelet aggregation (MPA) is reported by day.
Time Frame
Up through 11 days
Title
Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS)
Description
Return of baseline platelet function was assessed by Multiplate® ADP test and ADP test High Sensitivity (HS). Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. The agonist ADP was added to stirred whole blood after dilution (1:2 with 0.9% NaCl solution) in a final concentration of 6.4 µM (ADP Test) or in final concentration of 6.4 µM ADP plus 9.4 nM Prostaglandin E1 (PGE1) (ADPtest HS). Platelet aggregation was continuously recorded for 5 minutes and quantified as area under the aggregation curve (AUC=AU*min) of aggregation units (AU).
Time Frame
Up through 11 days
Title
Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hours Post-LD) by LTA (5 and 20 μM ADP)
Description
Maximum platelet aggregation (MPA) to 5 and 20 μM ADP were assessed by LTA. This outcome measure was not analyzed due to limited sample size.
Time Frame
Up through 11 days
Title
Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hrs Post-LD) by Multiplate® ADP Test and ADP Test High Sensitivity (HS)
Description
The Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. After adding 6.4 µM ADP (ADP test) or 6.4 µM ADP plus 9.4 nM Prostaglandin E1 (PGE1) (ADP test HS), area under the aggregation curve (AUC) was calculated. This outcome measure was not analyzed due to limited sample size.
Time Frame
Up through 11 days
Title
Platelet Function by LTA at 5 and 20 μM ADP
Description
MPA to 5 and 20 μM ADP were assessed by LTA.
Time Frame
24 hours post-loading dose
Title
Platelet Function by Multiplate® ADP Test and ADP Test HS
Description
The Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. After adding 6.4 µM ADP (ADP test) or 6.4 µM ADP plus 9.4 nM PGE1 (ADP test HS), area under the aggregation curve (AUC) were calculated.
Time Frame
24 hours post-loading dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Men or women ≥18 to <80 years of age who present with any one of the following:
symptoms of Acute Coronary Syndromes (ACS)
clinical symptoms of angina, or a positive stress test or who return for routine follow up angiography post stent placement in whom co-administration of aspirin and a thienopyridine (that is, clopidogrel, ticlopidine, or prasugrel) is not contraindicated
Exclusion Criteria:
Those presenting with ST-elevation MI (STEMI)
histories of refractory ventricular arrhythmias
an implanted defibrillator device
congestive heart failure (NYHA Class III or above) within 6 months prior to screening
significant hypertension
subjects with a history or clinical suspicion of cerebral vascular malformations, transient ischaemic attack, or stroke
bleeding disorders
women known to be pregnant, who have given birth within the past 90 days, or who are breastfeeding
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
Munich
ZIP/Postal Code
80636
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
22372531
Citation
Bernlochner I, Morath T, Brown PB, Zhou C, Baker BA, Gupta N, Jakubowski JA, Winters KJ, Schomig A, Kastrati A, Sibbing D. A prospective randomized trial comparing the recovery of platelet function after loading dose administration of prasugrel or clopidogrel. Platelets. 2013;24(1):15-25. doi: 10.3109/09537104.2011.654003. Epub 2012 Feb 28.
Results Reference
derived
Learn more about this trial
Study to Learn When Platelets Return to Normal After One Loading Dose of Anti-platelet Drugs in Patients With Symptoms of Acute Coronary Syndromes
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