Pharmacogenomics in Prediction of Cardiovascular Drugs Adverse Reaction

NCT05307718 | Unknown FDA Drug

• 1 other identifier: UIP-2020-02-8189
• Study Type: observational
• Target: 1,200
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Pharmacogenetics; adverse drug reactions; statins; DOAK; platelet aggregation inhibitors

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

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

Drug: Oral Anticoagulant, Direct-Acting

Cases

Cases will be subjects who have observed ADRs during follow-up: bleeding that meets the criteria of "major" or "non-major, clinically relevant bleeding (for anticoagulants and platelet aggregation inhibitors); muscle or liver lesions (for statins); any other serious ADR.

Drug: Oral Anticoagulant, Direct-Acting

Controls

Controls will be subjects in whom no ADRs were observed during the study

Drug: Oral Anticoagulant, Direct-Acting

Interventions

Oral Anticoagulant, Direct-Acting DRUG

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.

Also known as: HMG-CoA reductase inhibitors, platelet aggregation inhibitors from the P2Y12 receptor antagonist group

Cases; Controls; The basic cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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).

You may not qualify if:

• the existence of contraindications to the medicines of primary interest.

Sponsors & Collaborators

• Clinical Hospital Centre Zagreb: lead
• University of Zagreb School of Medicine: collaborator
• Croatian Science Foundation: collaborator

Study Sites (1)

UHC Zagreb

Zagreb, 10000, Croatia

RECRUITING

Related Publications (1)

• Bozina T, Ganoci L, Simicevic L, Vrkic Kirhmajer M, Mucalo I, Samardzic J, Palic J, Sliskovic AM, Trkulja V. Pharmacogenomics in the prediction of adverse effects of cardiovascular drugs: the PGx-CardioDrug project. Croat Med J. 2026 Jan 5;66(6):446-455.

  PMID: 41520206 DERIVED

Related Links

• Project web site

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions

Interventions

Factor Xa Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Anticoagulants; Hematologic Agents; Therapeutic Uses; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Lipid Regulating Agents

Study Officials

• Tamara Bozina, PhD

  University of Zagreb, Schooll of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tamara Bozina, PhD

CONTACT

+385 1 45 66 777; tamara.bozina@mef.hr

Livija Šimičević, PhD

CONTACT

+385 1 2388 888; lsimicev@kbc-zagreb.hr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Livija Simicevic

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: April 1, 2022
• Study Start: December 15, 2020
• Primary Completion: December 14, 2025
• Study Completion: December 14, 2025
• Last Updated: April 1, 2022

Record last verified: 2022-03

Locations

CR (1)