Trial Outcomes & Findings for Ranitidin Versus Omeprazole in Patients Taking Clopidogrel (NCT NCT01896557)

Results Overview

One week after starting double-blind, double-dummy, randomized therapy with ranitidin or omeprazole on patients treated with DAPT, platelet function will be compared with the method VerifyNow, in P2Y12 Reactivity Units.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

92 participants

Primary outcome timeframe

One week after randomized treatment exposure (omeprazole or ranitidine)

Results posted on

2018-07-06

Participant Flow

Participant milestones

Participant milestones
Measure	Omeprazole Omeprazole 20 mg (oral route) twice a day will be given to the subjects for one week. This intervention will be compared with ranitidin 150 mg (oral route) twice a day. omeprazole: Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.	Ranitidine Ranitidine 150 mg BID oral route was added to clopidogrel.
Clopidogrel Alone STARTED	44	48
Clopidogrel Alone COMPLETED	43	48
Clopidogrel Alone NOT COMPLETED	1	0
Clopidogrel + GI Protector STARTED	43	48
Clopidogrel + GI Protector COMPLETED	41	44
Clopidogrel + GI Protector NOT COMPLETED	2	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Omeprazole Omeprazole 20 mg (oral route) twice a day will be given to the subjects for one week. This intervention will be compared with ranitidin 150 mg (oral route) twice a day. omeprazole: Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.	Ranitidine Ranitidine 150 mg BID oral route was added to clopidogrel.
Clopidogrel Alone Adverse Event	1	0
Clopidogrel + GI Protector low adherence	1	1
Clopidogrel + GI Protector Reading error	1	3

Baseline Characteristics

Ranitidin Versus Omeprazole in Patients Taking Clopidogrel

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Omeprazole n=44 Participants Omeprazole 20 mg (oral route) twice a day will be given to the subjects for one week. This intervention will be compared with ranitidin 150 mg (oral route) twice a day. omeprazole: Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.	Ranitidine n=48 Participants Ranitidine 150 mg BID oral route was added to clopidogrel.	Total n=92 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
Age, Categorical Between 18 and 65 years	24 Participants n=5 Participants	26 Participants n=7 Participants	50 Participants n=5 Participants
Age, Categorical >=65 years	20 Participants n=5 Participants	22 Participants n=7 Participants	42 Participants n=5 Participants
Age, Continuous	62.6 years STANDARD_DEVIATION 10.9 • n=5 Participants	62.5 years STANDARD_DEVIATION 8.9 • n=7 Participants	62.6 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	14 Participants n=7 Participants	25 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	34 Participants n=7 Participants	67 Participants n=5 Participants

PRIMARY outcome

Timeframe: One week after randomized treatment exposure (omeprazole or ranitidine)

One week after starting double-blind, double-dummy, randomized therapy with ranitidin or omeprazole on patients treated with DAPT, platelet function will be compared with the method VerifyNow, in P2Y12 Reactivity Units.

Outcome measures

Outcome measures
Measure	Omeprazole n=41 Participants Omeprazole 20 mg (oral route) twice a day will be given to the subjects for one week. This intervention will be compared with ranitidin 150 mg (oral route) twice a day. omeprazole: Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.	Ranitidine n=44 Participants Ranitidine 150 mg BID oral route was added to clopidogrel.
Comparing Platelet Function of Patients on Dual Antiplatelet Therapy With ASA + Clopidogrel, Between the Groups Ranitidin and Omeprazole, After One Week of Randomized Treatment	173.54 P2Y12 Reactivity Units Standard Deviation 72.28	153.61 P2Y12 Reactivity Units Standard Deviation 70.12

PRIMARY outcome

Timeframe: One week after drug exposure (omeprazole/ranitidine); 2 weeks after baseline

One week after starting double-blind, double-dummy, randomized therapy with ranitidin or omeprazole on patients treated with DAPT, platelet function will be compared with the method VerifyNow, in percent Inhibition of Platelet Aggregation (IPA) from baseline. IPA was calculated as the percent change in aggregability from baseline, with the formula IPA = (on-treatment aggregability minus baseline aggregability)/baseline aggregability. Since baseline aggregation is always, per definition, equal or more than on-treatment aggregation, there is no possibility that this number might be negative.

Outcome measures

Outcome measures
Measure	Omeprazole n=41 Participants Omeprazole 20 mg (oral route) twice a day will be given to the subjects for one week. This intervention will be compared with ranitidin 150 mg (oral route) twice a day. omeprazole: Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.	Ranitidine n=44 Participants Ranitidine 150 mg BID oral route was added to clopidogrel.
Comparing Platelet Function of Patients on Dual Antiplatelet Therapy With ASA + Clopidogrel, Between the Groups Ranitidin and Omeprazole, Using VerifyNow Method.	17.4 Percentage Standard Deviation 33.1	30.1 Percentage Standard Deviation 31.3

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 week after drug exposure

Population: Platelet aggregation was measured after one week of randomized treatment therapy

After 1 week of randomization to ranitidin or omeprazole, the platelet function will also be analysed by other method: bioimpedance aggregometry with ADP 10 mcM as reagent

Outcome measures

Outcome measures
Measure	Omeprazole n=41 Participants Omeprazole 20 mg (oral route) twice a day will be given to the subjects for one week. This intervention will be compared with ranitidin 150 mg (oral route) twice a day. omeprazole: Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.	Ranitidine n=44 Participants Ranitidine 150 mg BID oral route was added to clopidogrel.
Comparison of the Primary Outcome With Bioimpedance Aggregometry	2 Ohms Standard Deviation 2.55	2.77 Ohms Standard Deviation 3.84

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 week after drug exposure

The main outcome will be compared on pre-specified subgroups: * elderly (age \> 65 yrs-old) versus non-elderly * male versus female * smoking versus non-smoking patients * obese (BMI \> 30 kg/m2) versus non-obese * diabetic versus non-diabetic * patients in use or not in use of statins * presence or not of genetic polymorphisms on cytochrome 2C19.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 week after drug exposure

Population: Platelet aggregation by PFA-100 was measured after one week of randomized treatment therapy

After 1 week of randomization to ranitidin or omeprazole, the platelet function will also be analysed by other method: PFA-100(Collagen/ADP cartridge).

Outcome measures

Outcome measures
Measure	Omeprazole n=33 Participants Omeprazole 20 mg (oral route) twice a day will be given to the subjects for one week. This intervention will be compared with ranitidin 150 mg (oral route) twice a day. omeprazole: Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.	Ranitidine n=36 Participants Ranitidine 150 mg BID oral route was added to clopidogrel.
Comparison of the Primary Outcome With PFA-100 (Collagen/ADP Cartridge)	95.1 seconds Standard Deviation 46.2	97.2 seconds Standard Deviation 79

Adverse Events

Omeprazole

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Ranitidine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Omeprazole n=44 participants at risk Omeprazole 20 mg (oral route) twice a day will be given to the subjects for one week. This intervention will be compared with ranitidin 150 mg (oral route) twice a day. omeprazole: Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.	Ranitidine n=48 participants at risk Ranitidine 150 mg BID oral route was added to clopidogrel.
Gastrointestinal disorders Dyspepsia	2.3% 1/44 • Number of events 1	0.00% 0/48

Additional Information

Remo Holanda de Mendonca Furtado

Heart Institute of University of Sao Paulo Medical School

Phone: +5511 26615058

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place