Pharmacogenomics in Prediction of Cardiovascular Drugs Adverse Reaction

Drug-Related Side Effects and Adverse Reactions Clinical Trial

Official title:

Pharmacogenomics in Prediction of Cardiovascular Drugs Adverse Reaction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05307718
• Other study ID #: UIP-2020-02-8189
• Status: Recruiting
• Start date: December 15, 2020
• Est. completion date: December 14, 2025

Study information

• Verified date: March 2022
• Source: Clinical Hospital Centre Zagreb
• Contact: Tamara Bozina, PhD
• Phone: +385 1 45 66 777
• Email: tamara.bozina[@]mef.hr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: December 14, 2025
• Est. primary completion date: December 14, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Drug-Related Side Effects and Adverse Reactions
• Pharmacogenetics

Intervention

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.

Locations

Country	Name	City	State
Croatia	UHC Zagreb	Zagreb

Sponsors (3)

Lead Sponsor	Collaborator
Clinical Hospital Centre Zagreb	Croatian Science Foundation, University of Zagreb School of Medicine

Country where clinical trial is conducted

Croatia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The overall project objective is to determine which pharmacogenes variants, together with clinical parameters, can be used as predictors of CV drug ADRs		4.5 years

External Links

•   Project web site