Trial Outcomes & Findings for PPI and Clopidogrel Response (NCT NCT01170533)

Last Updated: 2012-03-06

Results Overview

P2Y12 reactivity index which will be assessed by flow cytometry determination of vasodilator-stimulated phosphoprotein (VASP).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

1 week

Results posted on

2012-03-06

Participant Flow

The proposed study will have a prospective, randomized, cross-over design.

Participant milestones

Participant milestones
Measure	Omeprazole This was a prospective, open-label, two-sequence, three-period, randomized crossover study conducted in non-medicated healthy male subjects between the ages of 18 and 65 years. Subjects were randomized in a 1:1 fashion to take a PPI (omeprazole) concomitantly (CONC) or staggered (STAG) by 8-12 hours for one-week on a background of clopidogrel therapy. In particular, in the CONC regimen both drugs were taken in the morning, while in the STAG regimen clopidogrel was taken in the morning and the PPI (omeprazole)in the evening. After a 2-4 week washout period, subjects crossed-over treatment regimen. After completing these two treatment phases, subjects underwent another washout period of 2-4 weeks and were treated for 1 week with clopidogrel alone, without receiving PPI therapy (CLOP regimen).	Pantoprazole This was a prospective, open-label, two-sequence, three-period, randomized crossover study conducted in non-medicated healthy male subjects between the ages of 18 and 65 years. Subjects were randomized in a 1:1 fashion to take a PPI (pantoprazole) concomitantly (CONC) or staggered (STAG) by 8-12 hours for one-week on a background of clopidogrel therapy. In particular, in the CONC regimen both drugs were taken in the morning, while in the STAG regimen clopidogrel was taken in the morning and the PPI in the evening. After a 2-4 week washout period, subjects crossed-over treatment regimen. After completing these two treatment phases, subjects underwent another washout period of 2-4 weeks and were treated for 1 week with clopidogrel alone, without receiving PPI (pantoprazole) therapy (CLOP regimen).
Omeprazole Cross-over STARTED	20	0
Omeprazole Cross-over COMPLETED	20	0
Omeprazole Cross-over NOT COMPLETED	0	0
Pantoprazole Cross-over STARTED	0	20
Pantoprazole Cross-over COMPLETED	0	20
Pantoprazole Cross-over NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

PPI and Clopidogrel Response

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=25 Participants This was a prospective, open-label, two-sequence, three-period, randomized crossover study conducted in non-medicated healthy male subjects between the ages of 18 and 65 years. Subjects were randomized in a 1:1 fashion to take a PPI concomitantly (CONC) or staggered (STAG) by 8-12 hours for one-week on a background of clopidogrel therapy. In particular, in the CONC regimen both drugs were taken in the morning, while in the STAG regimen clopidogrel was taken in the morning and the PPI in the evening. After a 2-4 week washout period, subjects crossed-over treatment regimen. After completing these two treatment phases, subjects underwent another washout period of 2-4 weeks and were treated for 1 week with clopidogrel alone, without receiving PPI therapy (CLOP regimen). The PPI could be omeprazole (first phase) or pantoprazole (second phase).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous Omeprazole cross-over n=20	34 years STANDARD_DEVIATION 6 • n=5 Participants
Age Continuous Pantoprazole cross-over n=20	33 years STANDARD_DEVIATION 5 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 week

Population: A sample size of 18 patients was required to be able to detect a 10% absolute difference in PRI between both regimens with 80% power and 2-sided significance level of 0.05, assuming a 15% standard deviation for the difference between regimens.

P2Y12 reactivity index which will be assessed by flow cytometry determination of vasodilator-stimulated phosphoprotein (VASP).

Outcome measures

Outcome measures
Measure	Omeprazole Concomitant n=20 Participants Participants took omeprazole with clopidogrel concomitantly	Omeprazole Staggered n=20 Participants Participants took omeprazole with clopidogrel staggered	Pantoprazole Concomitant n=20 Participants Participants took pantoprazole with clopidogrel concomitantly	Pantoprazole Staggered n=20 Participants Participants took pantoprazole with clopidogrel staggered	Clopidogrel Only (Omeprazole Phase) n=20 Participants Participants took clopidogrel only	Clopidogrel Only (Pantoprazole Phase) n=20 Participants Participants took clopidogrel only
Platelet Function as Assessed by the P2Y12 Reactivity Index	56.1 Percentage of platelet reactivity index Standard Error 3.5	61.6 Percentage of platelet reactivity index Standard Error 3.4	56 Percentage of platelet reactivity index Standard Error 3.9	61 Percentage of platelet reactivity index Standard Error 3.9	48.8 Percentage of platelet reactivity index Standard Error 3.4	61.0 Percentage of platelet reactivity index Standard Error 3.9

Adverse Events

Omeprazole

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Pantoprazole

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dominick J. Angiolillo, MD, PhD

University of Florida-Jacksonville

Phone: 904-244-3933

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place