Trial Outcomes & Findings for Escalating Clopidogrel by Involving a Genetic Strategy - Thrombolysis In Myocardial Infarction 56 (NCT NCT01235351)
NCT ID: NCT01235351
Last Updated: 2019-11-15
Results Overview
The outcome measurement was on-treatment PRI determined through flow cytometric assessment of phosphorylation status of VASP.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
335 participants
Primary outcome timeframe
Approximately every 2 weeks for 8 weeks
Results posted on
2019-11-15
Participant Flow
335 patients from 32 sites were enrolled from October 2010 until September 2011.
335 patients enrolled, 2 patients not genotyped 333 patient allocated to initial treatment with 75 mg and 150 mg clopidogrel
Participant milestones
| Measure |
CYP2C19*2 Non-Carrier
Period 1: clopidogrel 75 mg and 150 mg for 14 days each Period 2: crossover to sequences of clopidogrel (75 mg first, then 150 mg, and 150 mg first, then 75 mg) for 14 days each.
|
CYP2C19*2 Carrier
Period 1: clopidogrel 75 mg and 150 mg for 14 days each Period 2: crossover to sequences of clopidogrel (225 mg first, then 300 mg, and 300 mg first, then 225 mg) for 14 days each.
|
|---|---|---|
|
Initial Treatment With 75 mg and 150 mg
STARTED
|
247
|
86
|
|
Initial Treatment With 75 mg and 150 mg
COMPLETED
|
237
|
82
|
|
Initial Treatment With 75 mg and 150 mg
NOT COMPLETED
|
10
|
4
|
|
Treatment With Different Dose Sequences
STARTED
|
233
|
82
|
|
Treatment With Different Dose Sequences
75 mg First and Then 150 mg
|
116
|
0
|
|
Treatment With Different Dose Sequences
150 mg First Then 75 mg
|
117
|
0
|
|
Treatment With Different Dose Sequences
225 mg First Then 300 mg
|
0
|
41
|
|
Treatment With Different Dose Sequences
300 mg First Then 225 mg
|
0
|
41
|
|
Treatment With Different Dose Sequences
COMPLETED
|
233
|
82
|
|
Treatment With Different Dose Sequences
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
CYP2C19*2 Non-Carrier
Period 1: clopidogrel 75 mg and 150 mg for 14 days each Period 2: crossover to sequences of clopidogrel (75 mg first, then 150 mg, and 150 mg first, then 75 mg) for 14 days each.
|
CYP2C19*2 Carrier
Period 1: clopidogrel 75 mg and 150 mg for 14 days each Period 2: crossover to sequences of clopidogrel (225 mg first, then 300 mg, and 300 mg first, then 225 mg) for 14 days each.
|
|---|---|---|
|
Initial Treatment With 75 mg and 150 mg
No follow-up sample
|
10
|
4
|
Baseline Characteristics
Escalating Clopidogrel by Involving a Genetic Strategy - Thrombolysis In Myocardial Infarction 56
Baseline characteristics by cohort
| Measure |
CYP2C19*2 Non-Carriers
n=247 Participants
|
CYP2C19*2 Carriers
n=86 Participants
|
Total
n=333 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
Mean Age
|
60.8 years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
58.6 years
STANDARD_DEVIATION 9.7 • n=7 Participants
|
60.2 years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
61 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
84 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
186 Participants
n=5 Participants
|
63 Participants
n=7 Participants
|
249 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Approximately every 2 weeks for 8 weeksPopulation: Non-carriers did not receive clopidogrel 225 mg or 300 mg
The outcome measurement was on-treatment PRI determined through flow cytometric assessment of phosphorylation status of VASP.
Outcome measures
| Measure |
CYP2C19*2 Carriers
n=82 Participants
Carrier of reduced function allele
|
CYP2C19*2 Non-Carriers
n=237 Participants
Not a carrier of reduced function allele
|
|---|---|---|
|
Comparisons of Vasodilator-stimulated Phosphoprotein (VASP) Phosphorylation Platelet Reactivity Index (PRI)
Clopidogrel 150 mg
|
62.4 % of PRI
Interval 58.1 to 66.7
|
46.9 % of PRI
Interval 44.3 to 49.1
|
|
Comparisons of Vasodilator-stimulated Phosphoprotein (VASP) Phosphorylation Platelet Reactivity Index (PRI)
Clopidogrel 75 mg
|
71.0 % of PRI
Interval 67.1 to 74.9
|
57.5 % of PRI
Interval 55.1 to 59.9
|
|
Comparisons of Vasodilator-stimulated Phosphoprotein (VASP) Phosphorylation Platelet Reactivity Index (PRI)
Clopidogrel 225 mg
|
54.0 % of PRI
Interval 49.4 to 58.5
|
—
|
|
Comparisons of Vasodilator-stimulated Phosphoprotein (VASP) Phosphorylation Platelet Reactivity Index (PRI)
Clopidogrel 300 mg
|
50.1 % of PRI
Interval 45.9 to 54.3
|
—
|
Adverse Events
CYP2C19*2 Carriers 75 mg
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
CYP2C19*2 Carriers 150 mg
Serious events: 5 serious events
Other events: 0 other events
Deaths: 0 deaths
CYP2C19*2 Carriers 225 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
CYP2C19*2 Carriers 300mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
CYP2C19*2 Noncarriers 75 mg
Serious events: 24 serious events
Other events: 0 other events
Deaths: 0 deaths
CYP2C19*2 Noncarriers 150 mg
Serious events: 16 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
CYP2C19*2 Carriers 75 mg
n=82 participants at risk
Patient with a carrier of genotype given 75 mg of the drug
|
CYP2C19*2 Carriers 150 mg
n=82 participants at risk
Patient with a carrier of genotype given 150 mg of the drug
|
CYP2C19*2 Carriers 225 mg
n=82 participants at risk
Patient with a carrier of genotype given 225 mg of the drug
|
CYP2C19*2 Carriers 300mg
n=82 participants at risk
Patient with a carrier of genotype given 300 mg of the drug
|
CYP2C19*2 Noncarriers 75 mg
n=233 participants at risk
Patients who are non-carriers of the genotype given 75 mg of the drug
|
CYP2C19*2 Noncarriers 150 mg
n=233 participants at risk
Patients who are non-carriers of the genotype given 150 mg of the drug
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorder
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/233
|
0.00%
0/233
|
|
Cardiac disorders
Cardiac disorders
|
1.2%
1/82 • Number of events 1
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/82
|
1.7%
4/233 • Number of events 4
|
1.3%
3/233 • Number of events 3
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/233
|
0.00%
0/233
|
|
General disorders
General disorders and administration site conditions
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/82
|
1.3%
3/233 • Number of events 3
|
0.43%
1/233 • Number of events 1
|
|
Infections and infestations
Infections and infestations
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/82
|
0.43%
1/233 • Number of events 1
|
0.43%
1/233 • Number of events 1
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/233
|
0.00%
0/233
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/82
|
0.00%
0/233
|
0.00%
0/233
|
|
Vascular disorders
Vascular disorders
|
0.00%
0/82
|
6.1%
5/82 • Number of events 5
|
0.00%
0/82
|
0.00%
0/82
|
6.9%
16/233 • Number of events 16
|
4.7%
11/233 • Number of events 11
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place