Phase 4 N=100 Randomized Basic Science

CES1 Crossover Trial of Clopidogrel and Ticagrelor

Myocardial Infarction · Thrombosis · Platelet Dysfunction

Bottom Line

View on ClinicalTrials.gov: NCT03161678 ↗

Enrolled (actual)

100

Serious AEs

0.0%

Results posted

May 2024

Primary outcome: Primary: Change in Maximal Platelet Aggregation in Response to Clopidogrel — 32.6; 50.8; 35.0 Percent Maximal Platelet Aggregation — p=<0.001

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: Clopidogrel (Drug); Ticagrelor (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: University of Maryland, Baltimore
Primary completion: Dec 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in Maximal Platelet Aggregation in Response to Clopidogrel	32.6; 50.8; 35.0	<0.001 sig
PRIMARY Change in Maximal Platelet Aggregation in Response to Ticagrelor	46.1; 47.8; 39.6	0.75

Summary

The purpose of this investigation is to evaluate when genetic variation in the carboxylesterase 1 (CES1) gene influences antiplatelet therapy response, as assessed by ex vivo platelet aggregometry, in healthy participants treated with clopidogrel and ticagrelor. We hypothesize that genetic variation in CES1 will significantly impact on-clopidogrel platelet aggregation while having a minimal effect in ticagrelor-treated subjects. Specific Aim: To conduct a prospective randomized crossover study of clopidogrel and ticagrelor in healthy individuals stratified by CES1 genotype. Participants will be recruited by CES1 genotype into a randomized crossover study of clopidogrel (75 mg daily for 7d) and ticagrelor (90 mg twice daily for 7d) with extensive phenotyping including ex vivo platelet aggregometry performed pre- and post-drug administration in order to assess the interaction of genotype and drug choice on on-treatment platelet function.

Eligibility Criteria

Inclusion Criteria

Of Amish descent
Age 18 to 75 years
Participant in the Phamacogenomics of Anti-Platelet Intervention (PAPI-1) Study or other Amish Research Center study, or a family member of an Amish Research Center study participant.

Exclusion Criteria

Clopidogrel or ticagrelor allergy
Platelet count 500,000 mm3
Hematocrit (Hct) 50%
Blood pressure > 160/95 mm Hg
Co-existing malignancy
Creatinine > 2.0 mg/dl
Aspartate transaminase (AST) or alanine transaminase (ALT) > 2 times the upper limit of normal
Thyroid-stimulating hormone (TSH) 5.50 mU/L
Pregnant or breast feeding
History of gastrointestinal bleeding, a major life-threatening bleeding event, active pathological bleeding, bleeding diathesis, or coagulopathy
History of stroke or transient ischemic attack, deep vein thrombosis, or atrial fibrillation
History of myocardial infarction, coronary artery bypass surgery, unstable angina, or angioplasty
History of sick sinus syndrome, 2nd or 3rd degree atrioventricular block, or bradycardia-related syncope
Type 1 or Type 2 diabetes mellitus
Surgery in the past 3 months or planned surgery in the next 3 months
Participant cannot willingly and safely discontinue medications that, in the opinion of the study physician would affect the outcomes to be measured for at least 1 week prior to study initiation through completion of the study
Participant is unwilling to discontinue taking vitamins and/or supplements that, in the opinion of the study physician would affect the outcomes to be measured for 1 week prior to the study initiation through the the completion of the study
Any other condition that would place prospective participants at unacceptable risk or render them unable to meet the requirements of the protocol in the opinion of the site investigator

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03161678). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.