Pharmacogenomics in Prediction of Cardiovascular Drugs Adverse Reaction

Summary

The research is planned as a prospective nested case-control study. The plan is to recruit about 1,200 consecutive subjects whose pharmacotherapy involves the drug(s) of interest within 4.5 years. The basic cohort - the subjects with the newly indicated indication for use: NOAC; platelet aggregation inhibitors from the P2Y12 receptor antagonist group; and HMG-CoA reductase inhibitors (statins); as monotherapy or without restriction with respect to any other concomitant pharmacotherapy. The ADRs will be analysed by CR by: age, gender, expectancy, severity, association, type (mechanism of event), and outcome, according to the classification of organ systems as well as association with the phenotype. Criteria for bleeding associated with the use of anticoagulant and antiplatelet therapy have been defined; as well as the myotoxicity and hepatotoxicity associated with statin therapy. Samples will be tested for biochemical, haematological, coagulation standard parameters and pharmacogenetic analyses of relevant genes depending on the used therapy. Pharmacogenetic analysis will be performed to genotype the polymorphisms of relevant pharmacogenes: Biological samples and clinical data will be anonymized plus all records of ADRs and other clinical variables will be protected. Possible drug-drug and drug-drug-gene interactions will be evaluated using the Clinical Decision Support System (CDSS) of Lexicomp, PharmGKB, the Flockhart Table, and other systems including panel consensus methods to determine the likelihood of an ADR being associated with drug interactions, and determine whether drug interactions contributed to the occurrence of ADRs to administered CV pharmacotherapy in subjects with variant pharmacogenes of interest (drug-drug-gene interaction). The overall project objective is to determine which pharmacogenes variants, together with clinical parameters, can be used as predictors of CV drug ADRs and are good candidates for inclusion in the clinical diagnostic panel for pre-emptive PGx testing.

Conditions

• Pharmacogenetics
• Drug-Related Side Effects and Adverse Reactions
• Cardiovascular Drugs

Interventions

DRUG

Oral Anticoagulant, Direct-Acting

Newly indicated indication for use: DOAC; platelet aggregation inhibitors from the P2Y12 receptor antagonist group; and HMG-CoA reductase inhibitors (statins); as monotherapy or without restriction with respect to any other concomitant pharmacotherapy. Subjects will be followed up during regular visits.

Sponsors & Collaborators

• University of Zagreb School of Medicine

  collaborator UNKNOWN

• Croatian Science Foundation

  collaborator OTHER_GOV

• Clinical Hospital Centre Zagreb

  lead OTHER

Principal Investigators

• Tamara Bozina, PhD · University of Zagreb, Schooll of Medicine

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-12-15

Primary Completion

2025-12-14

Completion

2025-12-14

FDA Drug

Yes

Countries

• Croatia

Study Locations