Clinical trial NCT05307718: Pharmacogenomics in Prediction of Cardiovascular Drugs Adverse Reaction
Official title: Pharmacogenomics in Prediction of Cardiovascular Drugs Adverse Reaction
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pharmacogenetics
Drug-Related Side Effects and Adverse Reactions
Cardiovascular Drugs
Keywords: Pharmacogenetics; adverse drug reactions; statins; DOAK; platelet aggregation inhibitors
Lead sponsor: Clinical Hospital Centre Zagreb
Sponsor class: OTHER
Collaborators: name: University of Zagreb School of Medicine
name: Croatian Science Foundation
First posted: 2022-04-01
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The primary cohort is represented by subjects who have a new indication for the administration of a) new oral anticoagulants (NOAC); b) platelet aggregation inhibitors from the P2Y12 receptor antagonist group (clopidogrel, prasugrel, ticagrelor); c) an HMG-CoA reductase inhibitor (statins); for the purpose of treatment or prophylaxis for at least 3 months; as monotherapy or without restriction with respect to any other concomitant pharmacological therapy.

Brief 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.


Eligibility criteria: Inclusion Criteria:

a) age 18 years or older; b) a new indication for the administration of any of the medicinal products of primary interest (NOAC, clopidogrel, prasugrel, ticagrelor, statins) for which at least a 3-month administration is predicted; c) signed informed consent (for repeated evaluations and donation of blood samples for genetic and eventual pharmacokinetic analysis).

Exclusion Criteria:

the existence of contraindications to the medicines of primary interest.

Primary outcomes:
measure: The overall project objective is to determine which pharmacogenes variants, together with clinical parameters, can be used as predictors of CV drug ADRs
timeFrame: 4.5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Zagreb
country: Croatia
facility: UHC Zagreb
Study officials:
affiliation: University of Zagreb, Schooll of Medicine
name: Tamara Bozina, PhD
role: PRINCIPAL_INVESTIGATOR
References: