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Trial record 53 of 1296 for:    ASPIRIN AND Platelet Aggregation

The Influence of Smoking Status on Prasugrel and Clopidogrel Treated Subjects Taking Aspirin and Having Stable Coronary Artery Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01260584
Recruitment Status : Completed
First Posted : December 15, 2010
Results First Posted : December 12, 2012
Last Update Posted : January 9, 2019
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Coronary Artery Disease
Interventions Drug: Prasugrel
Drug: Clopidogrel
Enrollment 110
Recruitment Details Phase 4, double-blind, double-dummy, randomized, crossover study of male and female subjects with stable CAD, who are currently receiving aspirin and do not have contraindications for a thienopyridine.
Pre-assignment Details Subjects will be stratified according to smoking status prior to being randomized to 1 of the 2 treatment sequences: prasugrel followed by clopidogrel or clopidogrel followed by prasugrel. There will be a 14-day Washout Period between Active Treatment Periods 1 and 2. All subjects will remain on the same dose of aspirin throughout the study.
Arm/Group Title Clopidogrel Then Prasugrel Smokers Clopidogrel Then Prasugrel Non-Smokers Prasugrel Then Clopidogrel Smokers Prasugrel Then Clopidogrel Non-Smokers
Hide Arm/Group Description

Clopidogrel 75 mg film-coated tablet daily dose x 10 days To maintain blinding, placebo film-coated tablets matching prasugrel in appearance will be given daily × 10 days to subjects in the clopidogrel treatment group. In addition, aspirin 81 mg to 325 mg daily will be taken.

Prasugrel : One 10 mg film-coated, oral tablet daily x 10 days. In addition, aspirin 81 mg to 325 mg daily will be taken.

Clopidogrel 75 mg film-coated tablet daily dose x 10 days To maintain blinding, placebo film-coated tablets matching prasugrel in appearance will be given daily × 10 days to subjects in the clopidogrel treatment group. In addition, aspirin 81 mg to 325 mg daily will be taken.

Prasugrel : One 10 mg film-coated, oral tablet daily x 10 days. In addition, aspirin 81 mg to 325 mg daily will be taken.

Prasugrel 10 mg film-coated tablet daily dose × 10 days. To maintain blinding, placebo film-coated tablets matching clopidogrel in appearance will be given daily × 10 days to subjects in the prasugrel treatment group. In addition, aspirin 81 mg to 325 mg daily will be taken.

Clopidogrel : One 75 mg film-coated, oral tablet daily x 10 days. In addition, aspirin 81 mg to 325 mg daily will be taken.

Prasugrel 10 mg film-coated tablet daily dose × 10 days. To maintain blinding, placebo film-coated tablets matching clopidogrel in appearance will be given daily × 10 days to subjects in the prasugrel treatment group. In addition, aspirin 81 mg to 325 mg daily will be taken.

Clopidogrel : One 75 mg film-coated, oral tablet daily x 10 days. In addition, aspirin 81 mg to 325 mg daily will be taken.

Period Title: Period 1
Started 27 28 27 28
Completed 27 28 25 27
Not Completed 0 0 2 1
Reason Not Completed
Protocol Violation             0             0             1             1
Adverse Event             0             0             1             0
Period Title: Period 2
Started 27 28 25 27
Completed 26 25 20 26
Not Completed 1 3 5 1
Reason Not Completed
Protocol Violation             0             2             3             1
Adverse Event             1             0             2             0
Withdrawal by Subject             0             1             0             0
Arm/Group Title Clopidogrel Then Prasugrel Smokers Clopidogrel Then Prasugrel Non-Smokers Prasugrel Then Clopidogrel Smokers Prasugrel Then Clopidogrel Non-Smokers Total
Hide Arm/Group Description

Clopidogrel 75 mg film-coated tablet daily dose x 10 days To maintain blinding, placebo film-coated tablets matching prasugrel in appearance will be given daily × 10 days to subjects in the clopidogrel treatment group. In addition, aspirin 81 mg to 325 mg daily will be taken.

Prasugrel : One 10 mg film-coated, oral tablet daily x 10 days. In addition, aspirin 81 mg to 325 mg daily will be taken.

Clopidogrel 75 mg film-coated tablet daily dose x 10 days To maintain blinding, placebo film-coated tablets matching prasugrel in appearance will be given daily × 10 days to subjects in the clopidogrel treatment group. In addition, aspirin 81 mg to 325 mg daily will be taken.

Prasugrel : One 10 mg film-coated, oral tablet daily x 10 days. In addition, aspirin 81 mg to 325 mg daily will be taken.

Prasugrel 10 mg film-coated tablet daily dose × 10 days. To maintain blinding, placebo film-coated tablets matching clopidogrel in appearance will be given daily × 10 days to subjects in the prasugrel treatment group. In addition, aspirin 81 mg to 325 mg daily will be taken.

Clopidogrel : One 75 mg film-coated, oral tablet daily x 10 days. In addition, aspirin 81 mg to 325 mg daily will be taken.

Prasugrel 10 mg film-coated tablet daily dose × 10 days. To maintain blinding, placebo film-coated tablets matching clopidogrel in appearance will be given daily × 10 days to subjects in the prasugrel treatment group. In addition, aspirin 81 mg to 325 mg daily will be taken.

Clopidogrel : One 75 mg film-coated, oral tablet daily x 10 days. In addition, aspirin 81 mg to 325 mg daily will be taken.

Total of all reporting groups
Overall Number of Baseline Participants 27 28 27 28 110
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
18
  66.7%
20
  71.4%
24
  88.9%
17
  60.7%
79
  71.8%
>=65 years
9
  33.3%
8
  28.6%
3
  11.1%
11
  39.3%
31
  28.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
59.3  (8.19) 59.6  (8.60) 56.7  (8.03) 61.9  (7.86) 59.4  (8.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
Female
8
  29.6%
7
  25.0%
9
  33.3%
7
  25.0%
31
  28.2%
Male
19
  70.4%
21
  75.0%
18
  66.7%
21
  75.0%
79
  71.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
Hispanic or Latino
6
  22.2%
4
  14.3%
3
  11.1%
3
  10.7%
16
  14.5%
Not Hispanic or Latino
21
  77.8%
24
  85.7%
24
  88.9%
25
  89.3%
94
  85.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
American Indian or Alaska Native
1
   3.7%
0
   0.0%
1
   3.7%
0
   0.0%
2
   1.8%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
7
  25.9%
6
  21.4%
4
  14.8%
6
  21.4%
23
  20.9%
White
19
  70.4%
22
  78.6%
22
  81.5%
22
  78.6%
85
  77.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
27 28 27 28 110
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
87.04  (15.243) 92.45  (18.433) 91.74  (20.109) 99.91  (23.096) 92.85  (19.740)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
172.3  (8.15) 172.5  (10.95) 172.5  (10.72) 173.7  (8.17) 172.8  (9.48)
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
29.20  (3.945) 31.12  (5.821) 30.70  (5.131) 32.94  (6.592) 31.01  (5.562)
Body Mass Index Group   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
<30 kg/m^2 19 10 13 10 52
>=30 kg/m^2 8 18 14 18 58
[1]
Measure Description: number participants less than 30 kilograms per square meter and number of participants greater than or equal to 30 kilograms per square meter
Smoking History  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
Never Smoked 0 14 0 11 25
Currently Smoke 27 0 27 0 54
Formerly Smoked 0 14 0 17 31
Alcohol Usage  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
Never consumed 6 9 8 8 31
Currently consumes 17 16 13 15 61
Formerly consumed 4 3 6 5 18
Cardiovascular history   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
Diabetes mellitus 5 9 8 9 31
Hypertension 19 16 21 20 76
Hyperlipidemia 26 24 26 27 103
Peripheral artery disease 3 0 5 2 10
[1]
Measure Description: Individual categories should not add up to equal total number participants in each arm.
CYP2C19 Phenotype Metabolic Rate  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
Poor 0 0 0 2 2
Intermediate 5 4 6 4 19
Extensive 18 23 20 22 83
Ultrarapid 3 1 1 0 5
not reported 1 0 0 0 1
CYP2C19 Phenotype Metabolic Extent  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 27 participants 28 participants 110 participants
Extensive metabolizers 21 24 21 22 88
Reduced metabolizers 5 4 6 6 21
Missing 1 0 0 0 1
1.Primary Outcome
Title Inhibition of Platelet Aggregation (IPA) in Prasugrel-treated and Clopidogrel-treated Smokers and Non-smokers Following 9 Days of Maintenance Therapy.
Hide Description IPA will be measured by the Accumetrics P2Y12 Assay Device. Response will be assessed in P2Y12 Reaction Units and as Platelet Reactivity Index (vasodilator-stimulated phosphoprotein assay).
Time Frame Baseline to day 10 for Active Treatment Periods 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
1 prasugrel smoker was unevaluable for this measure.
Arm/Group Title Prasugrel Smokers Prasugrel Non-Smokers Clopidogrel Smokers Clopidogrel Non-Smokers
Hide Arm/Group Description:
participants who currently smoke while receiving prasugrel as test medication during study
participants who do not currently smoke while receiving prasugrel as test medication during study
participants who currently smoke while receiving clopidogrel as test medication during study
participants who do not currently smoke while receiving clopidogrel as test medication during study
Overall Number of Participants Analyzed 50 52 47 54
Least Squares Mean (Standard Error)
Unit of Measure: percentage of device derived inhibition
70.3  (2.91) 65.6  (2.86) 38.6  (3.01) 30.9  (2.81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clopidogrel Smokers, Clopidogrel Non-Smokers
Comments For the sample size calculations for the co-primary endpoints, no Type 1 error rate was adjusted and both co-primary endpoints will be tested at the 0.05 level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0624
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.7
Confidence Interval (2-Sided) 95%
-0.4 to 15.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.11
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prasugrel Smokers, Clopidogrel Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 31.8
Confidence Interval (2-Sided) 95%
25.1 to 38.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.35
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Prasugrel Smokers, Prasugrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2440
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.8
Confidence Interval (2-Sided) 95%
-3.3 to 12.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.08
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Prasugrel Non-Smokers, Clopidogrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 34.7
Confidence Interval (2-Sided) 95%
28.4 to 41.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.17
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Prasugrel Non-Smokers, Clopidogrel Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 27.0
Confidence Interval (2-Sided) 95%
18.8 to 35.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.14
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Assessment of P2Y12 Reaction Units (PRU) by Treatment and Smoking Status
Hide Description

Day 10 occurs in each treatment period at which time data collections are made. 12.1.4. Responders and Poor Responders

Numerous studies have established an association between high on-treatment platelet reactivity with clopidogrel and an increased risk for post-PCI ischemic events. In this study, the percentages of “responders” and “poor responders” following treatment with prasugrel and clopidogrel were compared. Poor responders were defined based on an Accumetrics VerifyNow PRU >235 and a VASP PRI >50%, as assessed 24 hours after the 9th maintenance dose.

Time Frame Day 10 for Active Treatment Periods 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
1 prasugrel smoker was unevaluable for this measure.
Arm/Group Title Prasugrel Smokers Prasugrel Non-Smokers Clopidogrel Smokers Clopidogrel Non-Smokers
Hide Arm/Group Description:
participants who currently smoke while receiving prasugrel as test medication during study
participants who do not currently smoke while receiving prasugrel as test medication during study
participants who currently smoke while receiving clopidogrel as test medication during study
participants who do not currently smoke while receiving clopidogrel as test medication during study
Overall Number of Participants Analyzed 50 52 47 54
Least Squares Mean (Standard Error)
Unit of Measure: P2Y12 reaction unit
85.1  (8.99) 106.3  (8.73) 178.9  (9.26) 215.1  (8.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clopidogrel Smokers, Clopidogrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0048
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -36.2
Confidence Interval (2-Sided) 95%
-61.1 to -11.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 12.65
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prasugrel Smokers, Clopidogrel Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -93.8
Confidence Interval (2-Sided) 95%
-116.7 to -71.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 11.54
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Prasugrel Smokers, Prasugrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0924
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -21.2
Confidence Interval (2-Sided) 95%
-45.9 to 3.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 12.53
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Prasugrel Non-Smokers, Clopidogrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -108.8
Confidence Interval (2-Sided) 95%
-130.3 to -87.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 10.85
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Prasugrel Non-Smokers, Clopidogrel Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -72.6
Confidence Interval (2-Sided) 95%
-97.8 to -47.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 12.73
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Assessment of Vasodilator Stimulated Phosphoprotein (VASP) by Treatment and Smoking Status
Hide Description Day 10 occurs in each treatment period at which time data collections are made. Numerous studies have established an association between high on-treatment platelet reactivity with clopidogrel and an increased risk for post-PCI ischemic events. In this study, the percentages of “responders” and “poor responders” following treatment with prasugrel and clopidogrel were compared. Poor responders were defined based on an Accumetrics VerifyNow PRU >235 and a VASP PRI >50%, as assessed 24 hours after the 9th maintenance dose.
Time Frame Day 10 for Active Treatment Periods 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
1 prasugrel smoker was unevaluable for this measure.
Arm/Group Title Prasugrel Smokers Prasugrel Non-Smokers Clopidogrel Smokers Clopidogrel Non-Smokers
Hide Arm/Group Description:
participants who currently smoke while receiving prasugrel as test medication during study
participants who do not currently smoke while receiving prasugrel as test medication during study
participants who currently smoke while receiving clopidogrel as test medication during study
participants who do not currently smoke while receiving clopidogrel as test medication during study
Overall Number of Participants Analyzed 50 52 47 54
Least Squares Mean (Standard Error)
Unit of Measure: % vasodilator stimulated phosphoprotein
25.4  (2.64) 31.2  (2.59) 48.1  (2.73) 55.7  (2.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clopidogrel Smokers, Clopidogrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0423
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.6
Confidence Interval (2-Sided) 95%
-15.0 to -0.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.72
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prasugrel Smokers, Clopidogrel Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -22.7
Confidence Interval (2-Sided) 95%
-29.0 to -16.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.19
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Prasugrel Smokers, Prasugrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1184
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.8
Confidence Interval (2-Sided) 95%
-13.1 to 1.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.70
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Prasugrel Non-Smokers, Clopidogrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -24.5
Confidence Interval (2-Sided) 95%
-30.5 to -18.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.02
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Prasugrel Non-Smokers, Clopidogrel Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -16.9
Confidence Interval (2-Sided) 95%
-24.3 to -9.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.76
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Responder Rate by Treatment and Smoking Status Based on P2Y12 Reaction Units (PRU) <= 235
Hide Description [Not Specified]
Time Frame Day 10 for Active Treatment Periods 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
1 prasugrel smoker participant was not evaluable for this measure.
Arm/Group Title Prasugrel Smokers Prasugrel Non-Smokers Clopidogrel Smokers Clopidogrel Non-Smokers
Hide Arm/Group Description:
participants who currently smoke while receiving prasugrel as test medication during study
participants who do not currently smoke while receiving prasugrel as test medication during study
participants who currently smoke while receiving clopidogrel as test medication during study
participants who do not currently smoke while receiving clopidogrel as test medication during study
Overall Number of Participants Analyzed 50 52 47 54
Measure Type: Number
Unit of Measure: % participants with PRU <=235
98.0 96.2 76.6 61.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clopidogrel Smokers, Clopidogrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1331
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.06
Confidence Interval (2-Sided) 95%
0.80 to 5.32
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prasugrel Smokers, Prasugrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5813
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.99
Confidence Interval (2-Sided) 95%
0.17 to 23.65
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Prasugrel Smokers, Clopidogrel Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0127
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 16.54
Confidence Interval (2-Sided) 95%
1.85 to 148.23
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Prasugrel Non-Smokers, Clopidogrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 17.11
Confidence Interval (2-Sided) 95%
3.13 to 93.65
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Responder Rate by Treatment and Smoking Status Based on Platelet Reactivity Index (PRI) <= 50%
Hide Description Numerous studies have established an association between high on-treatment platelet reactivity with clopidogrel and an increased risk for post-PCI ischemic events. In this study, the percentages of “responders” and “poor responders” following treatment with prasugrel and clopidogrel were compared. Poor responders were defined based on an Accumetrics VerifyNow PRU >235 and a VASP PRI >50%, as assessed 24 hours after the 9th maintenance dose.
Time Frame Day 10 for Active Treatment Periods 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
1 prasugrel smoker participant was not evaluable for this measure.
Arm/Group Title Prasugrel Smokers Prasugrel Non-Smokers Clopidogrel Smokers Clopidogrel Non-Smokers
Hide Arm/Group Description:
participants who currently smoke while receiving prasugrel as test medication during study
participants who do not currently smoke while receiving prasugrel as test medication during study
participants who currently smoke while receiving clopidogrel as test medication during study
participants who do not currently smoke while receiving clopidogrel as test medication during study
Overall Number of Participants Analyzed 50 52 47 54
Measure Type: Number
Unit of Measure: % participants with PRI <=50%
96.0 82.7 51.1 44.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clopidogrel Smokers, Clopidogrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5684
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.34
Confidence Interval (2-Sided) 95%
0.49 to 3.67
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prasugrel Smokers, Prasugrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0447
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.70
Confidence Interval (2-Sided) 95%
1.05 to 42.92
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Prasugrel Smokers, Clopidogrel Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 58.64
Confidence Interval (2-Sided) 95%
6.80 to 505.58
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Prasugrel Non-Smokers, Clopidogrel Non-Smokers
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 11.71
Confidence Interval (2-Sided) 95%
2.95 to 46.52
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Characterization of the Pharmacokinetics (PK) Area Under Curve (AUC)(0-Last) of the Active Metabolite of Prasugrel and the Active Metabolite of Clopidogrel in Smokers and Non-smokers
Hide Description Blood samples for determination of plasma concentrations of the prasugrel active metabolite, clopidogrel active metabolite, and clopidogrel inactive metabolite will be collected following the administration of the 10th (last) maintenance dose of each of the 2 Active Treatment Periods at 0.5, 1, 2, 4, and 6 hours post-dose.
Time Frame After dose on Day 10 of Active Treatment Periods 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
1 Clopidogrel smoker participant was not evaluable for this measure.
Arm/Group Title Prasugrel Smokers Prasugrel Non-Smokers Clopidogrel Smokers Clopidogrel Non-Smokers
Hide Arm/Group Description:
participants who currently smoke while receiving prasugrel as test medication during study
participants who do not currently smoke while receiving prasugrel as test medication during study
participants who currently smoke while receiving clopidogrel as test medication during study
participants who do not currently smoke while receiving clopidogrel as test medication during study
Overall Number of Participants Analyzed 51 52 46 54
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
53.7
(41.2%)
48.1
(52.0%)
19.9
(55.8%)
16.2
(87.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prasugrel Smokers, Prasugrel Non-Smokers
Comments Prasugrel active metabolite R-138727
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 110.7
Confidence Interval (2-Sided) 90%
93.7 to 130.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Clopidogrel Smokers, Clopidogrel Non-Smokers
Comments active metabolite R-130964
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 118.4
Confidence Interval (2-Sided) 90%
99.8 to 140.4
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Characterization of the Pharmacokinetics (PK) Cmax of the Active Metabolite of Prasugrel and the Active Metabolite of Clopidogrel in Smokers and Non-smokers
Hide Description [Not Specified]
Time Frame After dose on Day 10 of Active Treatment Periods 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
1 clopidogrel smoker was not evaluable for this measure.
Arm/Group Title Prasugrel Smokers Prasugrel Non-Smokers Clopidogrel Smokers Clopidogrel Non-Smokers
Hide Arm/Group Description:
participants who currently smoke while receiving prasugrel as test medication during study
participants who do not currently smoke while receiving prasugrel as test medication during study
participants who currently smoke while receiving clopidogrel as test medication during study
participants who do not currently smoke while receiving clopidogrel as test medication during study
Overall Number of Participants Analyzed 51 52 46 54
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
42.9
(66.1%)
35.9
(80.7%)
14.1
(84.3%)
10.8
(116.3%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prasugrel Smokers, Prasugrel Non-Smokers
Comments Prasugrel active metabolite R-138727
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 117.9
Confidence Interval (2-Sided) 90%
94.4 to 147.3
Estimation Comments Estimation was based on the ratio of Geom. means between groups. Non-smoker is the denominator.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Clopidogrel Smokers, Clopidogrel Non-Smokers
Comments Clopidogrel active metabolite R-130964
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 123.8
Confidence Interval (2-Sided) 90%
98.6 to 155.4
Estimation Comments Estimation was based on the ratio of Geom. means between groups. Non-smoker is the denominator.
Time Frame [Not Specified]
Adverse Event Reporting Description 1 prasugrel non-smoker, 2 clopidogrel smokers, 1 clopidogrel non-smoker did not receive treatment in one period and were not determined to be "at-risk".
 
Arm/Group Title Prasugrel Smokers Prasugrel Non-Smokers Clopidogrel Smokers Clopidogrel Non-Smokers
Hide Arm/Group Description participants who currently smoke while receiving prasugrel as test medication during study participants who do not currently smoke while receiving prasugrel as test medication during study. 1 participant who started the arm was not "at risk". participants who currently smoke while receiving clopidogrel as test medication during study. 2 participants who started this arm were not "At risk". participants who do not currently smoke while receiving clopidogrel as test medication during study. 1 participant who started this arm was not "at risk".
All-Cause Mortality
Prasugrel Smokers Prasugrel Non-Smokers Clopidogrel Smokers Clopidogrel Non-Smokers
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Prasugrel Smokers Prasugrel Non-Smokers Clopidogrel Smokers Clopidogrel Non-Smokers
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/54 (7.41%)      0/55 (0.00%)      0/50 (0.00%)      0/54 (0.00%)    
Cardiac disorders         
Acute coronary syndrome *  1/54 (1.85%)  1 0/55 (0.00%)  0 0/50 (0.00%)  0 0/54 (0.00%)  0
Infections and infestations         
Cellulitis *  1/54 (1.85%)  1 0/55 (0.00%)  0 0/50 (0.00%)  0 0/54 (0.00%)  0
Osteomyelitis *  1/54 (1.85%)  1 0/55 (0.00%)  0 0/50 (0.00%)  0 0/54 (0.00%)  0
Staphylococcal infection *  1/54 (1.85%)  1 0/55 (0.00%)  0 0/50 (0.00%)  0 0/54 (0.00%)  0
Hepatitis B *  1/54 (1.85%)  1 0/55 (0.00%)  0 0/50 (0.00%)  0 0/54 (0.00%)  0
Injury, poisoning and procedural complications         
Tendon rupture *  1/54 (1.85%)  1 0/55 (0.00%)  0 0/50 (0.00%)  0 0/54 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Prasugrel Smokers Prasugrel Non-Smokers Clopidogrel Smokers Clopidogrel Non-Smokers
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/54 (9.26%)      6/55 (10.91%)      10/50 (20.00%)      6/54 (11.11%)    
Gastrointestinal disorders         
Nausea *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 0/54 (0.00%)  0
Toothache *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 0/54 (0.00%)  0
General disorders         
Vessel puncture site hemorrhage *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 1/54 (1.85%)  1
Fatigue *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 1/54 (1.85%)  1
Infections and infestations         
Nasopharyngitis *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 2/54 (3.70%)  2
Sinusitis *  0/54 (0.00%)  0 2/55 (3.64%)  2 0/50 (0.00%)  0 1/54 (1.85%)  1
Upper respiratory tract infection *  1/54 (1.85%)  1 2/55 (3.64%)  2 0/50 (0.00%)  0 0/54 (0.00%)  0
Injury, poisoning and procedural complications         
Limb injury *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 0/54 (0.00%)  0
Metabolism and nutrition disorders         
Gout *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 0/54 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Myalgia *  0/54 (0.00%)  0 1/55 (1.82%)  1 2/50 (4.00%)  2 1/54 (1.85%)  1
Arthralgia *  1/54 (1.85%)  1 0/55 (0.00%)  0 1/50 (2.00%)  1 0/54 (0.00%)  0
Pain in Extremity *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 0/54 (0.00%)  0
Nervous system disorders         
Dysgeusia *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 0/54 (0.00%)  0
Lethargy *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 0/54 (0.00%)  0
Psychiatric disorders         
Abnormal Dreams *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 0/54 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Cough *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 0/54 (0.00%)  0
Upper Respiratory Tract Congestion *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 0/54 (0.00%)  0
Skin and subcutaneous tissue disorders         
Ecchymosis *  2/54 (3.70%)  2 1/55 (1.82%)  1 0/50 (0.00%)  0 0/54 (0.00%)  0
Increased tendency to bruise *  1/54 (1.85%)  1 2/55 (3.64%)  2 0/50 (0.00%)  0 0/54 (0.00%)  0
Alopecia *  0/54 (0.00%)  0 0/55 (0.00%)  0 1/50 (2.00%)  1 0/54 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Sponsor reflects the following restrictive language in the Clinical Study Agreements: "If Daiichi Sankyo Inc. (DSI) identifies any of its confidential information as defined herein, it shall be deleted … Nothing in this publication section shall be taken as giving DSI any right of editorial control over any publication prepared by the Study Site."
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Brian Baker
Organization: Daiichi Sankyo
Phone: 973-944-2712
EMail: bbaker@dsi.com
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT01260584     History of Changes
Other Study ID Numbers: CS747S-B-U4002
First Submitted: December 13, 2010
First Posted: December 15, 2010
Results First Submitted: September 19, 2012
Results First Posted: December 12, 2012
Last Update Posted: January 9, 2019