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Pharmacogenomics of Anti-platelet Intervention-2 (PAPI-2) Study (PAPI-2)

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ClinicalTrials.gov Identifier: NCT01452152
Recruitment Status : Terminated (Terminated by study sponsor.)
First Posted : October 14, 2011
Results First Posted : June 28, 2016
Last Update Posted : March 5, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Alan Shuldiner, University of Maryland

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Cardiovascular Diseases
Acute Coronary Syndrome
Interventions Drug: clopidogrel
Drug: prasugrel
Enrollment 9
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Genotype-directed, Clopidogrel Genotype-directed, Prasugrel Standard of Care
Hide Arm/Group Description

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 extensive and ultrarapid metabolizers will receive clopidogrel.

clopidogrel: clopidogrel 75 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 intermediate and poor metabolizers will receive prasugrel.

prasugrel: Prasugrel 5-10 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the SOC group will not have CYP2C19 genotype analysis performed. They will receive dual anti-platelet therapy guided by the judgment of their treating physician according to standard medical practice irrespective of genotype.
Period Title: Overall Study
Started 5 0 4
Completed 0 0 0
Not Completed 5 0 4
Reason Not Completed
Study termination by sponsor             5             0             4
Arm/Group Title Genotype-directed, Clopidogrel Genotype-directed, Prasugrel Standard of Care Total
Hide Arm/Group Description

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 extensive and ultrarapid metabolizers will receive clopidogrel.

clopidogrel: clopidogrel 75 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 intermediate and poor metabolizers will receive prasugrel.

prasugrel: Prasugrel 5-10 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the SOC group will not have CYP2C19 genotype analysis performed. They will receive dual anti-platelet therapy guided by the judgment of their treating physician according to standard medical practice irrespective of genotype. Total of all reporting groups
Overall Number of Baseline Participants 5 0 4 9
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 0 participants 4 participants 9 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
3
  60.0%
3
  75.0%
6
  66.7%
>=65 years
2
  40.0%
1
  25.0%
3
  33.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 0 participants 4 participants 9 participants
Female
1
  20.0%
2
  50.0%
3
  33.3%
Male
4
  80.0%
2
  50.0%
6
  66.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 0 participants 4 participants 9 participants
Hispanic or Latino
0
   0.0%
1
  25.0%
1
  11.1%
Not Hispanic or Latino
5
 100.0%
3
  75.0%
8
  88.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 0 participants 4 participants 9 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
  25.0%
1
  11.1%
White
5
 100.0%
2
  50.0%
7
  77.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
  25.0%
1
  11.1%
1.Primary Outcome
Title Occurrence of Post-randomization Cardiovascular Events
Hide Description Cardiovascular events include non-fatal myocardial infarction, non-fatal stroke, definite or probable stent thrombosis (ARC definition) and death secondary to any cardiovascular cause.
Time Frame One year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Genotype-directed, Clopidogrel Genotype-directed, Prasugrel Standard of Care
Hide Arm/Group Description:

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 extensive and ultrarapid metabolizers will receive clopidogrel.

clopidogrel: clopidogrel 75 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 intermediate and poor metabolizers will receive prasugrel.

prasugrel: Prasugrel 5-10 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the SOC group will not have CYP2C19 genotype analysis performed. They will receive dual anti-platelet therapy guided by the judgment of their treating physician according to standard medical practice irrespective of genotype.
Overall Number of Participants Analyzed 5 0 4
Measure Type: Number
Unit of Measure: participants
0 0
2.Secondary Outcome
Title Occurrence of Bleeding Events
Hide Description Bleeding events will classified by the Bleeding Academic Research Consortium definition. The number of bleeding events will be tabulated.
Time Frame One year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Genotype-directed, Clopidogrel Genotype-directed, Prasugrel Standard of Care
Hide Arm/Group Description:

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 extensive and ultrarapid metabolizers will receive clopidogrel.

clopidogrel: clopidogrel 75 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 intermediate and poor metabolizers will receive prasugrel.

prasugrel: Prasugrel 5-10 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the SOC group will not have CYP2C19 genotype analysis performed. They will receive dual anti-platelet therapy guided by the judgment of their treating physician according to standard medical practice irrespective of genotype.
Overall Number of Participants Analyzed 5 0 4
Measure Type: Number
Unit of Measure: events
0 0
3.Secondary Outcome
Title Post-treatment Platelet Aggregation
Hide Description Platelet aggregation will be performed on a subset of subjects using VerifyNow P2Y12 which measures platelet reactivity due to the effect of a P2Y12. Values less than 180 P2Y12 Reaction Units (PRU) suggest evidence of a P2Y12 inhibitor effect. Platelet aggregation studies are optional and will not be used to modulate antiplatelet therapy.
Time Frame 10 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Optional platelet aggregation was performed in 3 of 5 participants randomized to the Genotype-directed, clopidogrel arm and 0 of 4 participants randomized to the Standard of Care arm.
Arm/Group Title Genotype-directed, Clopidogrel Genotype-directed, Prasugrel Standard of Care
Hide Arm/Group Description:

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 extensive and ultrarapid metabolizers will receive clopidogrel.

clopidogrel: clopidogrel 75 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 intermediate and poor metabolizers will receive prasugrel.

prasugrel: Prasugrel 5-10 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the SOC group will not have CYP2C19 genotype analysis performed. They will receive dual anti-platelet therapy guided by the judgment of their treating physician according to standard medical practice irrespective of genotype.
Overall Number of Participants Analyzed 3 0 0
Mean (Standard Deviation)
Unit of Measure: percentage of inhibition
33.7  (18.5)
4.Secondary Outcome
Title Health Care Resource Utilization and Cost-effectiveness
Hide Description [Not Specified]
Time Frame One year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This outcome measure has zero total participants analyzed because health care resource utilization and cost-effectiveness data was not collected due to the early termination of the trial.
Arm/Group Title Genotype-directed, Clopidogrel Genotype-directed, Prasugrel Standard of Care
Hide Arm/Group Description:

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 extensive and ultrarapid metabolizers will receive clopidogrel.

clopidogrel: clopidogrel 75 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 intermediate and poor metabolizers will receive prasugrel.

prasugrel: Prasugrel 5-10 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the SOC group will not have CYP2C19 genotype analysis performed. They will receive dual anti-platelet therapy guided by the judgment of their treating physician according to standard medical practice irrespective of genotype.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Occurrence of Adverse Events
Hide Description The number of subjects reporting any AEs will be tabulated.
Time Frame One year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Genotype-directed, Clopidogrel Genotype-directed, Prasugrel Standard of Care
Hide Arm/Group Description:

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 extensive and ultrarapid metabolizers will receive clopidogrel.

clopidogrel: clopidogrel 75 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 intermediate and poor metabolizers will receive prasugrel.

prasugrel: Prasugrel 5-10 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the SOC group will not have CYP2C19 genotype analysis performed. They will receive dual anti-platelet therapy guided by the judgment of their treating physician according to standard medical practice irrespective of genotype.
Overall Number of Participants Analyzed 5 0 4
Measure Type: Number
Unit of Measure: participants
1 3
6.Secondary Outcome
Title Composite of All-cause Death, Myocardial Infarction (MI), Stroke and Repeat Revascularization
Hide Description [Not Specified]
Time Frame One year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Genotype-directed, Clopidogrel Genotype-directed, Prasugrel Standard of Care
Hide Arm/Group Description:

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 extensive and ultrarapid metabolizers will receive clopidogrel.

clopidogrel: clopidogrel 75 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 intermediate and poor metabolizers will receive prasugrel.

prasugrel: Prasugrel 5-10 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the SOC group will not have CYP2C19 genotype analysis performed. They will receive dual anti-platelet therapy guided by the judgment of their treating physician according to standard medical practice irrespective of genotype.
Overall Number of Participants Analyzed 5 0 4
Measure Type: Number
Unit of Measure: participants
0 0
Time Frame One year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Genotype-directed, Clopidogrel Genotype-directed, Prasugrel Standard of Care
Hide Arm/Group Description

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 extensive and ultrarapid metabolizers will receive clopidogrel.

clopidogrel: clopidogrel 75 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 intermediate and poor metabolizers will receive prasugrel.

prasugrel: Prasugrel 5-10 mg/day plus aspirin 81-162 mg/day for one year

Participants randomized to the SOC group will not have CYP2C19 genotype analysis performed. They will receive dual anti-platelet therapy guided by the judgment of their treating physician according to standard medical practice irrespective of genotype.
All-Cause Mortality
Genotype-directed, Clopidogrel Genotype-directed, Prasugrel Standard of Care
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Genotype-directed, Clopidogrel Genotype-directed, Prasugrel Standard of Care
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/5 (0.00%)      0/0      1/4 (25.00%)    
Cardiac disorders       
chest pain - cardiac  1  0/5 (0.00%)  0 0/0  0 1/4 (25.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Genotype-directed, Clopidogrel Genotype-directed, Prasugrel Standard of Care
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/5 (20.00%)      0/0      1/4 (25.00%)    
Cardiac disorders       
atrial fibrillation  1  1/5 (20.00%)  1 0/0  0 0/4 (0.00%)  0
Gastrointestinal disorders       
gastritis  1  0/5 (0.00%)  0 0/0  0 1/4 (25.00%)  1
Infections and infestations       
hepatitis viral  1  0/5 (0.00%)  0 0/0  0 1/4 (25.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
The study was terminated early by the sponsor due to low enrollment.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Dr. Alan R. Shuldiner
Organization: University of Maryland School of Medicine
Phone: 410-706-1623
Responsible Party: Alan Shuldiner, University of Maryland
ClinicalTrials.gov Identifier: NCT01452152     History of Changes
Other Study ID Numbers: HP-00047385
9U01HL105198-06 ( U.S. NIH Grant/Contract )
First Submitted: October 10, 2011
First Posted: October 14, 2011
Results First Submitted: February 18, 2016
Results First Posted: June 28, 2016
Last Update Posted: March 5, 2018