CES1 Crossover Trial of Clopidogrel and Ticagrelor

Browse trials for

• Myocardial Infarction 2,744
• Thrombosis 1,508

Keywords

• Pharmacogenetics
• Carboxylesterase 1 (CES1)
• Antiplatelet therapy

Myocardial Infarction

2,744 studies on the registry are indexed under Myocardial Infarction; 418 are open to participants now.

This study's enrollment of 111 is below the median of 148 across 1,595 interventional studies indexed under Myocardial Infarction.

Lead sponsor

University of Maryland, Baltimore is the lead sponsor of 687 studies on the registry; 130 are open to participants now.

Of its 90 completed or terminated interventional studies of FDA-regulated products, 63 (70%) have results posted.

Study arms

• Active comparator
  Wild-Type Genotype

  Research subjects with wild type CES1 genotypes will be studied before and after oral ingestion of clopidogrel (75 mg/d for 8 days) and ticagrelor (90 mg twice daily for 8 days) treatment.

  Drug: Clopidogrel · Drug: Ticagrelor

• Experimental
  Carriers of the CES1 G143E Mutation

  Research subjects who carry the CES1 G143E allele (rs71647871) will be studied before and after oral ingestion of clopidogrel (75 mg/d for 8 days) and ticagrelor (90 mg twice daily for 8 days) treatment.

  Drug: Clopidogrel · Drug: Ticagrelor

• Experimental
  Carriers of CES1 rs7498748 Mutation

  Research subjects who carry a CES1 rs7498748 minor allele will be studied before and after oral ingestion of clopidogrel (75 mg/d for 8 days) and ticagrelor (90 mg twice daily for 8 days) treatment.

  Drug: Clopidogrel · Drug: Ticagrelor

Interventions

• DrugClopidogrel

  Clopidogrel (75 mg/d for 8 days) will be administered. Measures of pharmacodynamics will be assessed pre- and post-drug administration.

  Also known as: Plavix

• DrugTicagrelor

  Ticagrelor (90 mg twice daily for 8 days) will be administered. Measures of pharmacodynamics will be assessed pre- and post-drug administration.

  Also known as: Brilinta

Primary outcomes

1. Change in Maximal Platelet Aggregation in Response to Clopidogrel

   Ex vivo platelet aggregometry was performed in platelet rich plasma (PRP) after stimulation with 20 μM adenosine diphosphate (ADP) at 2 time points (at baseline prior to drug administration and on the 8th day of clopidogrel \[75mg/d\]). Maximum platelet aggregation is recorded by the platelet aggregometer as a percentage. Data shown below represent the maximum platelet aggregation value obtained at baseline minus the maximum platelet aggregation value obtained after clopidogrel administration. Thus, values recorded below represent changes from baseline at day 8 and the unit is percent maximum aggregation. Higher reported values represent a greater reduction in platelet aggregation while lower reported values signify a smaller reduction in platelet aggregation when comparing baseline and post-clopidogrel visits.

   Time frame: 8 days of exposure to clopidogrel (change from baseline at day 8 reported)

2. Change in Maximal Platelet Aggregation in Response to Ticagrelor

   Ex vivo platelet aggregometry was performed in platelet rich plasma (PRP) after stimulation with 20 μM adenosine diphosphate (ADP) at 2 time points (at baseline prior to drug administration and on the 8th day of ticagrelor \[90 mg twice daily\]). Maximum platelet aggregation is recorded by the platelet aggregometer as a percentage. Data shown below represent the maximum platelet aggregation value obtained at baseline minus the maximum platelet aggregation value obtained after ticagrelor administration. Thus, values recorded below represent changes from baseline at day 8 and the unit is percent maximum aggregation. Higher reported values represent a greater reduction in platelet aggregation while lower reported values signify a smaller reduction in platelet aggregation when comparing baseline and post-ticagrelor visits.

   Time frame: 8 days of independent exposure to ticagrelor (change from baseline at day 8 reported)

Baseline characteristics

3 further baseline measures are reported on the registry.

Publications

• Lewis JP, Ryan KA, Streeten EA, Whitlatch HB, Daue M, Tanner K, Perry JA, O'Connell JR, Shuldiner AR, Mitchell BD. Randomized evaluation of the loss-of-function carboxylesterase 1 (CES1) G143E variant on clopidogrel and ticagrelor pharmacodynamics. Clin Transl Sci. 2024 Nov;17(11):e70079. doi: 10.1111/cts.70079. PubMed 39576732 ↗

Study documents

• Protocol and statistical analysis plan · Mar 5, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — It is possible that deidentified data will be deposited into large public databases as per NIH data sharing policies (e.g. database of Genotypes and Phenotypes \[dbGAP\], Pharmacogenomics Knowledgebase \[PharmGKB\]). Data to be shared would include, but not limited to, anthropometric data, study outcome data, and relevant covariate data used in statistical models of association. It is anticipated that data would be available after the completion of the trial. The data will be obtained from the participants and the study-related research procedures.