Trial Outcomes & Findings for Clopidogrel Pharmacogenetics (PGX) Bench to Bedside (NCT NCT01341600)
NCT ID: NCT01341600
Last Updated: 2024-01-30
Results Overview
Adenosine diphosphate (ADP) mediated platelet aggregation measured 4 hours post-dose of clopidogrel on Day 1.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
18 participants
Primary outcome timeframe
Day 1, 4 hours post clopidogrel dose
Results posted on
2024-01-30
Participant Flow
Participant milestones
| Measure |
Poor Metabolizers
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI (NCT00799396)) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Intermediate Metabolizers
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI (NCT00799396)) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Extensive Metabolizers
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI (NCT00799396)) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
|---|---|---|---|
|
Clopidogrel 75 mg
STARTED
|
6
|
6
|
6
|
|
Clopidogrel 75 mg
COMPLETED
|
6
|
6
|
6
|
|
Clopidogrel 75 mg
NOT COMPLETED
|
0
|
0
|
0
|
|
Clopidogrel 150 mg
STARTED
|
6
|
6
|
6
|
|
Clopidogrel 150 mg
COMPLETED
|
6
|
6
|
6
|
|
Clopidogrel 150 mg
NOT COMPLETED
|
0
|
0
|
0
|
|
Clopidogrel 225 mg
STARTED
|
6
|
6
|
6
|
|
Clopidogrel 225 mg
COMPLETED
|
6
|
6
|
6
|
|
Clopidogrel 225 mg
NOT COMPLETED
|
0
|
0
|
0
|
|
Clopidogrel Plus Omeprazole
STARTED
|
5
|
5
|
4
|
|
Clopidogrel Plus Omeprazole
COMPLETED
|
5
|
5
|
4
|
|
Clopidogrel Plus Omeprazole
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Clopidogrel Pharmacogenetics (PGX) Bench to Bedside
Baseline characteristics by cohort
| Measure |
Poor Metabolizers
n=6 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Intermediate Metabolizers
n=6 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Extensive Metabolizers
n=6 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
6 participants
n=7 Participants
|
6 participants
n=5 Participants
|
18 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Day 1, 4 hours post clopidogrel doseAdenosine diphosphate (ADP) mediated platelet aggregation measured 4 hours post-dose of clopidogrel on Day 1.
Outcome measures
| Measure |
Poor Metabolizers
n=6 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Intermediate Metabolizers
n=6 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Extensive Metabolizers
n=6 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
|---|---|---|---|
|
Change in Platelet Aggregation Following Therapy With Clopidogrel
Clopidogrel 75mg
|
62.9 percentage of aggregation
Standard Deviation 14.7
|
68.1 percentage of aggregation
Standard Deviation 5.0
|
62.5 percentage of aggregation
Standard Deviation 3.4
|
|
Change in Platelet Aggregation Following Therapy With Clopidogrel
Clopidogrel 150mg
|
63.2 percentage of aggregation
Standard Deviation 9.3
|
57.8 percentage of aggregation
Standard Deviation 7.2
|
53.9 percentage of aggregation
Standard Deviation 12.9
|
|
Change in Platelet Aggregation Following Therapy With Clopidogrel
Clopidogrel 300mg
|
53.3 percentage of aggregation
Standard Deviation 15.2
|
47.8 percentage of aggregation
Standard Deviation 13.6
|
38.6 percentage of aggregation
Standard Deviation 10.9
|
PRIMARY outcome
Timeframe: 4 hours post Day 8 doseADP mediated platelet aggregation measured 4 hours post Day 8 clopidogrel dose
Outcome measures
| Measure |
Poor Metabolizers
n=6 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Intermediate Metabolizers
n=6 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Extensive Metabolizers
n=6 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
|---|---|---|---|
|
Change in Platelet Aggregation Following Therapy With Clopidogrel
Clopidogrel 75mg
|
55.0 percentage of aggregation
Standard Deviation 14.5
|
37.8 percentage of aggregation
Standard Deviation 8.2
|
31.3 percentage of aggregation
Standard Deviation 7.3
|
|
Change in Platelet Aggregation Following Therapy With Clopidogrel
Clopidogrel 150mg
|
44.2 percentage of aggregation
Standard Deviation 15.0
|
33.2 percentage of aggregation
Standard Deviation 6.0
|
25.1 percentage of aggregation
Standard Deviation 7.1
|
|
Change in Platelet Aggregation Following Therapy With Clopidogrel
Clopidogrel 300mg
|
32.6 percentage of aggregation
Standard Deviation 10.7
|
25.7 percentage of aggregation
Standard Deviation 6.0
|
19.5 percentage of aggregation
Standard Deviation 6.9
|
SECONDARY outcome
Timeframe: Baseline, Day 8The change in maximum platelet aggregation in response to ADP 4-hours post dose on day 8 of therapy with clopidogrel and omeprazole will be compared to the baseline measure of platelet aggregation at day 1 prior to drug therapy
Outcome measures
| Measure |
Poor Metabolizers
n=5 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Intermediate Metabolizers
n=5 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Extensive Metabolizers
n=4 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
|---|---|---|---|
|
Change in Platelet Aggregation Following Therapy With Clopidogrel and Omeprazole
|
11.6 percentage of aggregation
Standard Deviation 11.9
|
27.9 percentage of aggregation
Standard Deviation 9.3
|
37.5 percentage of aggregation
Standard Deviation 3.2
|
SECONDARY outcome
Timeframe: Baseline, 0.25, 0.5, 1, 2, and 4 hoursThe level of the active clopidogrel metabolite will be measured at at 0.25, 0.5, 1, 2, and 4 hours after the Day One dose is administered for pharmacokinetic analysis. The analysis will measure the Area Under the Curve.
Outcome measures
| Measure |
Poor Metabolizers
n=6 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Intermediate Metabolizers
n=6 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Extensive Metabolizers
n=6 Participants
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
|---|---|---|---|
|
Level of Active Clopidogrel Metabolite
Clopidogrel 75mg
|
17.4 ng h/mL
Standard Deviation 19
|
33.3 ng h/mL
Standard Deviation 37
|
32.7 ng h/mL
Standard Deviation 25
|
|
Level of Active Clopidogrel Metabolite
Clopidogrel 150mg
|
24.2 ng h/mL
Standard Deviation 26
|
43.8 ng h/mL
Standard Deviation 35
|
53.6 ng h/mL
Standard Deviation 35
|
|
Level of Active Clopidogrel Metabolite
Clopidogrel 300mg
|
36 ng h/mL
Standard Deviation 35
|
73.7 ng h/mL
Standard Deviation 53
|
80.4 ng h/mL
Standard Deviation 24
|
Adverse Events
Poor Metabolizers
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Intermediate Metabolizers
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Extensive Metabolizers
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Poor Metabolizers
n=6 participants at risk
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Intermediate Metabolizers
n=6 participants at risk
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
Extensive Metabolizers
n=6 participants at risk
Healthy subjects who have been genotyped for CYP2C19\*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396).
Clopidogrel, Omeprazole: Over a 6 week period participants will be given:
75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/6 • Six weeks
|
0.00%
0/6 • Six weeks
|
16.7%
1/6 • Six weeks
|
|
Nervous system disorders
vasovagal reaction
|
0.00%
0/6 • Six weeks
|
16.7%
1/6 • Six weeks
|
0.00%
0/6 • Six weeks
|
|
Infections and infestations
skin infection
|
0.00%
0/6 • Six weeks
|
0.00%
0/6 • Six weeks
|
16.7%
1/6 • Six weeks
|
Additional Information
Richard Horenstein M.D., Associate Professor of Medicine
University of Maryland School of Medicine
Phone: 410-706-0154
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place